17524 results for "fc 26 coins Buyfc26coins.com is EA Sports official for FC 26 coins They are definitely a top seller..rG5l"

in 77.12 milliseconds.

• MultiOMICS study of a pair of infant monozygotic twins with concordant B-cell ALL (WGS)

  B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common cancer in childhood. Studying identical twins with B-cell ALL provides a unique and tractable model for deciphering the developmental timing of pre- and post-natal mutations contributing to clonal evolution. To date, this has mainly focused on major cytogenetic subgroups of childhood B-cell ALL, including MLL fusions, ETV6-RUNX1, hyperdiploidy, and BCR-ABL1. However, formal demonstration of the prenatal origin and “backtracking” the natural history of the leukemia remains understudied in “B-other”/Normal Karyotype (NK) B-cell ALL. To characterize the genetic landscape of this particular leukemia subtype, we performed whole genome DNA- and B-cell receptor (BCR)- on a pair of 8-month-old monozygotic twins diagnosed with concordant “B-other”/NK B-cell ALL.

  Dataset EGAD00001005017

• MultiOMICS study of a pair of infant monozygotic twins with concordant B-cell ALL (WGBS)

  B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common cancer in childhood. Studying identical twins with B-cell ALL provides a unique and tractable model for deciphering the developmental timing of pre- and post-natal mutations contributing to clonal evolution. To date, this has mainly focused on major cytogenetic subgroups of childhood B-cell ALL, including MLL fusions, ETV6-RUNX1, hyperdiploidy, and BCR-ABL1. However, formal demonstration of the prenatal origin and “backtracking” the natural history of the leukemia remains understudied in “B-other”/Normal Karyotype (NK) B-cell ALL. To characterize the epigenetic landscape of this particular leukemia subtype, we performed DNA bisulfite-sequencing on a pair of 8-month-old monozygotic twins diagnosed with concordant “B-other”/NK B-cell ALL.

  Dataset EGAD00001005018

• Low-coverage whole genome sequencing for a highly selective cohort of severe COVID-19 patients

  We generated a dataset consisting of 79 VCF files, and respective FASTQ and CRAM files, methodically generated using the GLIMPSE1 imputation algorithm leveraging the 1000 Genomes Project Phase 3 dataset as the reference panel of haplotypes. In total this dataset is composed of approximately 325 GB of FASTQ data, 156 GB of CRAM data, and 6 GB of VCF data. Our samples were specifically derived from sequenced DNA from a highly selective cohort of patients, mostly comprised of Iberian Populations in Spain (IBS) individuals but also containing some individuals with other genetic backgrounds, who presented severe COVID-19 symptoms during the initial wave of the SARS-CoV-2 pandemic in Madrid, Spain. On average, each VCF file in this rich dataset contains 9.49 million high-confidence single nucleotide variants [95%CI: 9.37 million - 9.61 million].

  Dataset EGAD00001011363

• Multimodal plasma and urinary cell-free DNA profiling improves risk stratification in newly diagnosed prostate cancer

  Prostate cancer (PCa) is a heterogeneous disease, impeding early detection and risk stratification. Liquid biopsies (LBx) enable minimally invasive tumor profiling, but circulating tumor-derived DNA (ctDNA) detection remains difficult, particularly in early-stage PCa. We developed a multimodal LBx approach combining genomic and epigenomic cell-free DNA (cfDNA) features in plasma and urine from newly diagnosed PCa patients to improve early characterization of PCa and risk stratification of aggressive disease. Plasma and urine samples from 55 localized PCa (lPCa) patients, 18 advanced PCa (aPCa) patients, and 36 cancer-free controls were subjected to low-coverage whole-genome sequencing and methylated DNA immunoprecipitation sequencing to assess fragmentation, chromosomal instability, and methylation in cfDNA. This complementary approach yielded a 45% ctDNA detection rate in newly diagnosed PCa. Major differences were observed between aPCa and controls, reflecting increasing signals with tumor progression. Epigenomic cfDNA features differentiated lPCa from aPCa, and ctDNA was detected in 46% of PCa patients with prostate-specific antigen <10 ng/ml, suggesting potential for risk stratification. This study highlights the value of multimodal LBx approaches for early characterization of primary PCa and identification of aggressive disease at initial diagnosis. Integration into clinical workflows could complement diagnostics and support personalized decision-making tailored to patients’ PCa risk profiles. 

  Study EGAS00001008195

• An isogenic human iPSC model unravels neurodevelopmental abnormalities in SMA

  Whether neurodevelopmental defects underlie the selective neuronal death that characterizes neurodegenerative diseases is becoming an intriguing question. To address it, we focused on the motor neuron (MN) disease Spinal Muscular Atrophy (SMA), caused by reduced levels of the ubiquitous protein SMN. Taking advantage of the first isogenic human induced pluripotent stem cell-derived SMA model that we have generated and a spinal cord organoid system, here we report that the relative and temporal expression of early neural progenitor and MN markers is altered in SMA. Furthermore, the corrected isogenic controls only partially reverse these abnormalities. These findings raise the relevant clinical implication that SMN-increasing treatments might not fully amend SMA pathological phenotypes. The approach we have taken demonstrates that the discovery of new disease mechanisms is greatly improved by using human isogenic models. Moreover, our study implies that SMA has a developmental component that might trigger the MN degeneration.

  Study EGAS00001007259

• Slim Initiative in Genomic Medicine for the Americas (SIGMA): Diabetes in Mexico Study (DMS)

  The ~52,000 sample Type 2 Diabetes Exome Sequencing project is a collaboration of six consortia with various funding mechanisms that have joined together to investigate genetic variants for type 2 diabetes (T2D) using the largest T2D case/control sample set compiled to date. This includes samples from: Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Genetics of Type 2 Diabetes (GoT2D) Exome Sequencing Project (ESP) Slim Initiative in Genomic Medicine for the Americas: Type 2 Diabetes (SIGMA T2D) Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCAMP) Progress in Diabetes Genetics in Youth (ProDIGY) This data generated from the SIGMA Diabetes in Mexico Study (DMS) was part of the Slim Initiative in Genomic Medicine for the Americas: Type 2 Diabetes (SIGMA T2D), which is an international research consortium funded by the Carlos Slim Foundation that seeks to identify the genetic risk factors for type 2 diabetes (T2D) in Mexico and Latin America and translate those findings into improved treatment and prevention of diabetes. The SIGMA T2D project has sequenced and genotyped more than 13,000 samples from Mexican and Mexican Americans. The individuals were obtained from over 20 cohorts across the 6 consortia that are listed in Table 1. The strategy was to perform deep exome sequencing of individuals, 24,991 with T2D and 24,953 controls, divided among five ancestry groups: Europeans, East Asians, South Asians, American Hispanics, and African Americans. The T2D-GENES, ProDIGY and SIGMA studies, sequencing was performed at the Broad Institute using the Agilent v2 capture reagent or Illumina Rapid Capture on Illumina HiSeq machines. Please note that while we summarize the full sample list in publications and below, two of the cohorts below are not in dbGaP, due to the samples not being consented for deposition. This includes the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) study and Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) study. The Exome Sequencing Project (ESP) was deposited in dbGaP as part of their initial study and the phs numbers for that project can be found here: https://esp.gs.washington.edu/drupal/dbGaP_Releases. Table 1. 52,000 sample T2D Case/Control Whole Exome Sequencing Studies Ancestry Consortia Study Countries of Origin # Cases # Controls African American T2D-GENES Project 1 Jackson Heart Study US 500 526 African American T2D-GENES Project 1 Wake Forest School of Medicine Study US 518 530 African American ESP Exome Sequencing Project (ESP) US 467 1374 African American T2D-GENES Follow up study BioMe Biobank Program (BioMe) US 1297 1256 East Asian T2D-GENES Project 1 Korea Association Research Project Korea 526 561 East Asian T2D-GENES Project 1& Follow up Study Singapore Diabetes Cohort Study; Singapore Prospective Study Program Singapore (Chinese) 1486 1568 East Asian T2D-GENES Follow up study Korea SNUH South Korea 450 475 East Asian T2D-GENES Follow up study Research Studies in Hong Kong (Hong Kong) Hong Kong 493 485 European T2D-GENES Project 1 Ashkenazi US, Israel 506 355 European T2D-GENES Project 1 Metabolic Syndrome in Men Study (METSIM) Finland 484 498 European GoT2D Finland-United States Investigation of NIDDM Genetics (FUSION) Study Finland 472 476 European GoT2D Kooperative Gesundheitsforschung in der Region Augsburg (KORA) Germany 97 90 European GoT2D UK Type 2 Diabetes Genetics Consortium (UKT2D) UK 322 320 European GoT2D Malmo-Botnia Study Finland, Sweden 478 443 European LuCamp Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) Denmark 997 997 European ESP Exome Sequencing Project (ESP) US 390 2843 European T2D-GENES Follow up study Genetics of Diabetes and Audit Research Tayside Study (GoDARTS) Scotland, UK 960 966 European T2D-GENES Follow up study Framingham Heart Study (FHS) US 396 596 Hispanic T2D-GENES Project 1 San Antonio Family Heart Study, San Antonio Family Diabetes/ Gallbladder Study, Veterans Administration Genetic Epidemiology Study, and the Investigation of Nephropathy and Diabetes Study Family Component US 272 218 Hispanic T2D-GENES Project 1 & SIGMAv2 Starr County, Texas US 1762 1738 Hispanic SIGMAv1 Mexico City Diabetes Study Mexico 281 549 Hispanic SIGMAv1 & v2 Multiethnic Cohort (MEC) US 1476 1443 Hispanic SIGMAv1 & v2 UNAM/INCMNSZ Diabetes Study (UIDS) Mexico 1998 1977 Hispanic SIGMAv1 & v2 Diabetes in Mexico Study (DMS) Mexico 1522 1546 Multi ethnic ProDIGY Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) US 3097 0 Multi ethnic ProDIGY SEARCH for Diabetes in Youth (SEARCH) US 553 0 South Asian T2D-GENES Project 1 London Life Sciences Population Study (LOLIPOP) UK (Indian Asian) 531 538 South Asian T2D-GENES Project 1 & Follow up study Singapore Indian Eye Study Singapore (Indian Asian) 1640 1478 South Asian T2D-GENES Follow up study Pakistan Genomic Resource (PGR) Pakistan 914 932 The Diabetes in Mexico Study (DMS) study contributed 1,522 cases and 1,546 controls to the 52k T2D exome sequencing study.

  Study phs001388

• Slim Initiative in Genomic Medicine for the Americas (SIGMA): Mexico City Diabetes Study (MCDS)

  The ~52,000 sample Type 2 Diabetes Exome Sequencing project is a collaboration of six consortia with various funding mechanisms that have joined together to investigate genetic variants for type 2 diabetes (T2D) using the largest T2D case/control sample set compiled to date. This includes samples from: Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Genetics of Type 2 Diabetes (GoT2D) Exome Sequencing Project (ESP) Slim Initiative in Genomic Medicine for the Americas: Type 2 Diabetes (SIGMA T2D) Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCAMP) Progress in Diabetes Genetics in Youth (ProDIGY) This data generated from the SIGMA Mexico City Diabetes Study was part of the Slim Initiative in Genomic Medicine for the Americas: Type 2 Diabetes (SIGMA T2D), which is an international research consortium funded by the Carlos Slim Foundation that seeks to identify the genetic risk factors for type 2 diabetes (T2D) in Mexico and Latin America and translate those findings into improved treatment and prevention of diabetes. The SIGMA T2D project has sequenced and genotyped more than 13,000 samples from Mexican and Mexican Americans. The individuals were obtained from over 20 cohorts across the 6 consortia that are listed in Table 1. The strategy was to perform deep exome sequencing of individuals, 24,991 with T2D and 24,953 controls, divided among five ancestry groups: Europeans, East Asians, South Asians, American Hispanics, and African Americans. The T2D-GENES, ProDIGY and SIGMA studies, sequencing was performed at the Broad Institute using the Agilent v2 capture reagent or Illumina Rapid Capture on Illumina HiSeq machines. Please note that while we summarize the full sample list in publications and below, two of the cohorts below are not in dbGaP, due to the samples not being consented for deposition. This includes the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) study and Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) study. The Exome Sequencing Project (ESP) was deposited in dbGaP as part of their initial study and the phs numbers for that project can be found here: https://esp.gs.washington.edu/drupal/dbGaP_Releases Table 1. 52,000 sample T2D Case/Control Whole Exome Sequencing Studies Ancestry Consortia Study Countries of Origin # Cases # Controls African American T2D-GENES Project 1 Jackson Heart Study US 500 526 African American T2D-GENES Project 1 Wake Forest School of Medicine Study US 518 530 African American ESP Exome Sequencing Project (ESP) US 467 1374 African American T2D-GENES Follow up study BioMe Biobank Program (BioMe) US 1297 1256 East Asian T2D-GENES Project 1 Korea Association Research Project Korea 526 561 East Asian T2D-GENES Project 1& Follow up Study Singapore Diabetes Cohort Study; Singapore Prospective Study Program Singapore (Chinese) 1486 1568 East Asian T2D-GENES Follow up study Korea SNUH South Korea 450 475 East Asian T2D-GENES Follow up study Research Studies in Hong Kong (Hong Kong) Hong Kong 493 485 European T2D-GENES Project 1 Ashkenazi US, Israel 506 355 European T2D-GENES Project 1 Metabolic Syndrome in Men Study (METSIM) Finland 484 498 European GoT2D Finland-United States Investigation of NIDDM Genetics (FUSION) Study Finland 472 476 European GoT2D Kooperative Gesundheitsforschung in der Region Augsburg (KORA) Germany 97 90 European GoT2D UK Type 2 Diabetes Genetics Consortium (UKT2D) UK 322 320 European GoT2D Malmo-Botnia Study Finland, Sweden 478 443 European LuCamp Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention, and Care (LuCamp) Denmark 997 997 European ESP Exome Sequencing Project (ESP) US 390 2843 European T2D-GENES Follow up study Genetics of Diabetes and Audit Research Tayside Study (GoDARTS) Scotland, UK 960 966 European T2D-GENES Follow up study Framingham Heart Study (FHS) US 396 596 Hispanic T2D-GENES Project 1 San Antonio Family Heart Study, San Antonio Family Diabetes/ Gallbladder Study, Veterans Administration Genetic Epidemiology Study, and the Investigation of Nephropathy and Diabetes Study Family Component US 272 218 Hispanic T2D-GENES Project 1 & SIGMAv2 Starr County, Texas US 1762 1738 Hispanic SIGMAv1 Mexico City Diabetes Study Mexico 281 549 Hispanic SIGMAv1 & v2 Multiethnic Cohort (MEC) US 1476 1443 Hispanic SIGMAv1 & v2 UNAM/INCMNSZ Diabetes Study (UIDS) Mexico 1998 1977 Hispanic SIGMAv1 & v2 Diabetes in Mexico Study (DMS) Mexico 1522 1546 Multi ethnic ProDIGY Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) US 3097 0 Multi ethnic ProDIGY SEARCH for Diabetes in Youth (SEARCH) US 553 0 South Asian T2D-GENES Project 1 London Life Sciences Population Study (LOLIPOP) UK (Indian Asian) 531 538 South Asian T2D-GENES Project 1 & Follow up study Singapore Indian Eye Study Singapore (Indian Asian) 1640 1478 South Asian T2D-GENES Follow up study Pakistan Genomic Resource (PGR) Pakistan 914 932

  Study phs001375

• Synthetic modeling reveals HOXB genes are critical for the initiation and maintenance of human leukemia

  Study EGAS00001003627

• A Single-Cell and Spatial Atlas of Early Human Olfactory Development

  The human nasal region is a complex anatomical structure comprising neural crest- and placode-derived lineages, yet its developmental dynamics in humans remain poorly understood due to limited access to fetal tissue and challenges in resolving its spatial and cellular complexity. We built a single-cell and spatial transcriptomic atlas of the human fetal nasal region from 10 fetuses spanning post-conceptional weeks 7 to 12. Using snRNA-seq, we identify 34 cell types in the fetal nasal region and reconstruct lineage trajectories in the olfactory epithelium (OE). Spatial analyses uncover regionalized OE organization, dorsoventral gradients of olfactory receptors (ORs) and high-resolution OR expression. Combining snRNAseq and MERFISH, we reveal early onset of OR gene expression, with most olfactory sensory neurons (OSNs) following the one neuron-one receptor rule already during the first trimester. This work provides the first integrated molecular and spatial framework of early human nasal region and it provides an unprecedented molecular blueprint of the human olfactory system development. In addition, this study offers a foundational resource for embryologists and developmental biologists investigating sensory neurogenesis, epithelial patterning, and congenital diseases.

  Study EGAS50000001203

• Long-read sequencing identifies a common transposition haplotype predisposing for CLCNKB deletions

  This dataset contains CLCNKA/CLCNKB locus alignment data from 27 patients with Bartter syndrome and structural variants encompassing the CLCNKB gene. Due to data protection regulations and in accordance with the patient consent, only relevant alignments from the following regions are shared: hg19: chr1:16,300,000-16,400,000 hg38 (linked read dataset only): chr1:16,000,000-16,100,000 Methods to generate libaries were: long-range amplicon PCR (24 samples), targeted long-fragment enrichment (Samplix/Xdrop technology, 4 samples), long-read whole genome (PacBio Sequel II HiFi reads, 3 samples), 10X linked read short read whole genome (1 sample).

  Dataset EGAD00001011064

• Low T cell diversity is associated with poor outcome in bladder cancer - Bulk TCRseq data

  T cells are crucial effector cells in the endogenous defense against cancer, yet the clinical impact of their quantity, diversity, and dynamics remains underexplored. In this study we performed bulk TCRseq on tumor and serial blood samples from patients with muscle invasive (n patients = 119) or non-muscle invasive bladder cancer (n patients = 30). The goal was to investigate the clinical relevance of the blood and tumor TCR repertoire in patients with bladder cancer.

  Study EGAS50000000940

• Exome Sequencing in an Ancestrally Diverse Autism Cohort

  Autism spectrum disorder (ASD) is a collection of neurodevelopmental disorders manifested by impaired social communication, repetitive behaviors, and restricted interests. We performed whole exome sequencing (WES) on a total of 754 individuals from 195 families, including 222 probands with ASD, from diverse ancestral backgrounds. We identified potentially pathogenic variants in known and novel ASD or neurodevelopmental disease genes.

  Study phs003603

• Mechanisms on relapse after allogeneic hematopoietic cell transplantation in CMML

  Disease relapse is a major cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT), and mechanisms on relapse still remain to be elucidated. We experienced a patient with chronic myelomonocytic leukemia (CMML) who underwent haploidentical HCT from his daughter and developed relapse. To understand the mechanisms on relapse after HCT, we analyze blood samples at HCT and at relapse.

  Study JGAS000317

• Genome-wide differential DNA methylation signatures in pediatric acute lymphoblastic leukemia

  The aim of our study is to provide a comprehensive analysis of DNA methylation in a large collection of primary pediatric acute lymphoblastic leukemia (ALL) samples taken at diagnosis and relapse of the disease as well as non-leukemic control blood cells from healthy individuals. Complementary gene expression data available at the Gene Expression Omnibus under series GSE26878.

  Study EGAS00000000135

• INTEGRATIVE MOLECULAR ANALYSIS OF SKIN TUMORS FROM CYLD CUTANEOUS SYNDROME PATIENTS

  CYLD cutaneous syndrome (CCS) is a rare autosomal dominant disorder characterized by germline CYLD mutations and by multiple benign skin tumors dependent on NF-kB pathway. We assembled a large cohort of CCS rare skin tumors that was profiled with whole exome or genome sequencing, RNA sequencing and methylation arrays to better understand genetic mechanisms of CCS tumorogenesis.

  Study EGAS50000000247

• Whole-genome and transcriptome sequencing of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma

  Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (pcAECyTCL) is a rare variant of cutaneous T-cell lymphoma with an aggressive clinical course and a very poor prognosis. We subjected tumor biopsies from patients with pcAECyTCL to whole-genome sequencing and RNA-sequencing to investigate genomic alterations and deregulated gene expression in the disease.

  Study EGAS00001004332

• Genetic landscape of pediatric Adrenocortical Tumor

  Paediatric adrenocortical carcinoma is a rare malignancy with poor prognosis. Here we analyse 37 adrenocortical tumours (ACTs) by whole-genome, whole-exome and/or transcriptome sequencing. Collectively, these findings demonstrate the nature, timing and potential prognostic significance of key genetic alterations in paediatric ACT and outline a hypothetical model of paediatric adrenocortical tumorigenesis.

  Study EGAS00001000257

• DAC of the STIC project

  Ovarian high-grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as ‘p53 signatures’, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinomas (STIC) lesions, which, in turn, progress into invasive HGSC that readily spread to the ovary and disseminate around the peritoneal cavity. We recently investigated the genomic landscape of early- and late-stage HGSC and found higher ploidy in late-stage (median 3.1) than early-stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole genome duplication observed in late-stage disease are determined early in the evolution of HGSC, we analysed archival formalin-fixed paraffin-embedded samples (FFPE) from five HGSC patients. p53 signatures and STIC lesions were laser-capture microdissected and sequenced using shallow whole genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of whole genome duplication, arises early in HGSC, and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development.

  Dac EGAC50000000227

• Deep sequencing analysis of human iPSC-specific SNVs in donor cell population

  CR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation. The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001000605

• Deep sequencing of S7EPC genome

  PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation. The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001000607

• Subclonal analysis in S7RE2 and S7RE14 iPS cells

  PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation. The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001000608

• Validation of SNVs found by Exome-seq in S2-SF1, -SF5 and -SF9 hiPSCs

  PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation. The library will be sequenced either by HiSeq or MiSeq. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001000631

• An integrated single-cell reference atlas of the human endometrium

  This dataset includes both the anchor scRNA-seq and snRNA-seq datasets used to build the Human Endometrial Cell Atlas (HECA). HECA provides a comprehensive definition of endometrial cell types and states throughout the menstrual cycle in donor with and without endometriosis. It identifies consensus cell types across datasets generated by teams worldwide, as well as previously unreported cell types, all of which are validated and mapped in situ using spatial transcriptomics. Processed data is available from ArrayExpress with accession number E-MTAB-14039. See Marečková, M., Garcia-Alonso, L., Moullet, M. et al. An integrated single-cell reference atlas of the human endometrium. Nat Genet 56, 1925–1937 (2024) https://doi.org/10.1038/s41588-024-01873-w for more information.

  Dataset EGAD00001015446

• Intractable Cancer Therapy Development through a New Target Identification by Molecular Profiling

  We collected the cancerous tissues of the primary and recurrence tumors from the same patient with recurrent / metastatic breast cancer, and the purpose of this study is to find the characteristics of recurrent / metastatic breast cancers by carrying out a "molecular profiling", mainly the exome sequence analysis of these tissues.

  Study JGAS000075

• A distinct monocyte cellular state links systemic immune dysregulation to pulmonary impairment in long COVID

  This is an independent cohort of Long COVID patients recruited from a rehabilitation centre. These patients had Long COVID from 8 months to more than 2 years since their acute COVID-19 disease. PBMC from these patients were collected and single cell transcriptomics dataset was generated.

  Study EGAS50000001216

• Osteosarcoma WGS on multiple tissue samples from six patients

  Osteosarcoma is a primary bone tumor that exhibits a complex genome characterized by gross chromosomal abnormalities. Osteosarcoma patients often develop metastatic disease, resulting in limited therapeutic options and poor survival rates. To gain knowledge on the mechanisms underlying osteosarcoma heterogeneity and metastatic process, it is important to obtain a detailed profile of the genomic alterations that accompany osteosarcoma progression. Therefore, in this study we performed WGS on multiple tissue samples from six patients with osteosarcoma, including the treatment naïve biopsy of the primary tumor, resection of the primary tumor after neoadjuvant chemotherapy, local recurrence and distant metastases.

  Dataset EGAD50000000475

• cfRRBS on cfDNA from pediatric cancer

  In the clinical management of pediatric solid tumors, histological examination of tumor tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumor is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumor samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of pediatric tumors using cell-free reduced representation bisulfite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumor type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in pediatric oncology in a cost-effective and minimally invasive manner.

  Study EGAS00001004194

• Combinatorial Indexed 10x Genomics Single-Cell ATAC-seq on Human Cerebral Cortex

  Single-cell chromatin accessibility profiling (scATAC) using droplet fluidics (10x Genomics) is inherently limited in throughput due to the number of available indexed droplets. This study leverages single-cell combinatorial indexing workflows with modified adapter designs to enable indexed tagmentation and superloading of pre-indexed nuclei into the 10x Genomics scATAC workflow, enabling a substantial increase in the number of cell profiles that can be obtained per channel. This workflow, 10x single-cell combinatorial indexed ATAC-seq (txsciATAC), is demonstrated on human brain tissue (middle frontal gyrus), along with mouse brain tissue to enable doublet and crosstalk assessment. This study includes all human data and includes a single preparation taken through nuclei isolation and indexed tagmentation using 96 indexes then split to produce two datasets, one targeting 20k cells and one targeting 70k, each using a single channel of the 10x Chromium controller.

  Study phs003497

• Sequencing data from the study "Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer"

  This dataset consists of 71 whole-genome samples and 47 RNA-seq samples. All WGS samples are provided in .bam format and RNA-seq samples are provided as .fq.gz (paired-end). Next-generation sequencing data on whole genomes were processed by aligning sequencing reads to a reference genome (NCBI build 37/hg19) using bwa-mem (0.7.13-r1126).

  Dataset EGAD50000001978

• Paroxysmal Neurological Disorders - rare epilepsies

  We are sequencing the exomes of patients with paroxysmal neurological disorders mainly focusing on migraine and epilepsy. Cases are collected from performance sites of members of EuroEPINOMICS. Most cases have a strong family history. The study sample will include both cases and controls.

  Dataset EGAD00001000647

• GoNL release 5 raw SNV calls

  These files contain a total of 20.4M SNVs and the complete information output by the GATK UnifiedGenotyper v1.4 on all 767 GoNL samples. These calls are not trio-aware and all genotypes were reported regardless of their quality. Both filtered and passing calls are reported in these files. Filtered calls include (1) calls failing our VQSR threshold and (2) calls in the GoNL inaccessible genome.

  Dataset EGAD00001000743

• Prognostic and immunomodulatory consequences of ERV expression in ovarian cancer

  The dataset contains transcriptional data obtained using total RNA sequencing on a Illumina machin. 59 samples are from the Hammersmith Hospital (HH) cohort of human primary ovarian tumours and 20 samples are from ovarian cancer cell lines Kuramochi (3 replicates) and Ovsaho (2 replicates) treated with 1 uM DNMTi guadecitabine or vehicle, at an early (day 5) or late (day 8) timepoint.

  Dataset EGAD00001006589

• Asthma in the Lives of Families Today (ALOFT)

  Social interactions and the overall psychosocial environment have a demonstrated impact on health, particularly for people living in disadvantaged urban areas. Here we investigated the effect of psychosocial experiences on gene expression in peripheral blood immune cells of 251 children with asthma in Metro Detroit. Participants were included from an ongoing longitudinal study Asthma in the Lives of Families Today (ALOFT; recruited from November 2010-July 2018. The ALOFT project was established to identify the behavioral and biological pathways through which family social environments impact youth with asthma.In version 1 we used RNA-sequencing and a new machine learning approach to identify transcriptional signatures of 19 variables including psychosocial factors, blood cell composition and asthma symptoms. Using longitudinal data collected from a subset of the participants we showed that transcriptional signatures track the longitudinal changes in measured phenotypes. Importantly, we found 169 genes associated with asthma that are regulated by psychosocial factors, and 344 significant gene-environment interactions for gene expression levels. These results demonstrate that immune gene expression mediates the link between negative psychosocial experiences and asthma risk.In version 2, we focused on pubertal development. We identified substantial gene expression changes associated with age and pubertal development. We showed that genetic effects on gene expression change dynamically during pubertal development. Gene expression changes during puberty are correlated with gene expression changes associated with asthma and may explain sex differences in prevalence. Our results show that molecular data used to study the genetics of early onset diseases should consider pubertal development as an important factor that modifies the transcriptome.Version 3 uses single cell RNA-seq to study the dynamics of the transcriptional response to glucocorticoids in activated Peripheral Blood Mononuclear Cells from 96 African American children. We employed novel statistical approaches to calculate a mean-independent measure of gene expression variability and a measure of transcriptional response pseudotime. Using these approaches, we demonstrated that glucocorticoids reverse the effects of immune stimulation on both gene expression mean and variability. Our novel measure of gene expression response dynamics, based on the diagonal linear discriminant analysis, separated individual cells by response status on the basis of their transcriptional profiles and allowed us to identify different dynamic patterns of gene expression along the response pseudotime. We identified genetic variants regulating gene expression mean and variability, including treatment-specific effects, and demonstrated widespread genetic regulation of the transcriptional dynamics of the gene expression response.Version 4 adds scATAC-seq in activated peripheral blood mononuclear cells (PBMC) from 16 children with asthma with phytohemagglutinin (PHA) or lipopolysaccharide (LPS), and treated with dexamethasone (DEX), an anti-inflammatory glucocorticoid. We analyzed changes in chromatin accessibility, measured transcription factor motif activity, and identified treatment and cell-type specific transcription factors that drive changes in both gene expression mean and variability. We observed strong positive linear dependence between motif response and their target gene expression changes, but negative in variability changes. This result suggests that an increase of transcription factor binding tightens the variability of gene expression around the mean. We then annotated genetic variants in chromatin accessibility peaks and response motifs followed by computational fine-mapping of eQTL signals from a pediatric asthma cohort. We found that eQTLs were 5-fold enriched in peaks with response motifs and refined the credible set for 410 asthma risk genes, with 191 having the causal variant in response motifs. These results enhance the understanding of molecular mechanisms for asthma risk variants mediated by gene expression.

  Study phs002182

• Targeted bisulfite sequencing

  Raw reads from targeted bisulfite sequencing. The SureSelect Methyl-Seq target enrichment system (Agilent Technologies, Inc., CA, USA) was used to prepare bisulfite sequencing libraries from blood DNA samples of lymphoma patients (Ly1, Ly2), healthy family members (Ly8, Ly9, Ly10, Ly11, Ly12, Ly13 and Ly14), baseline controls (Control1-5), DNMT3A mutation carriers (Id5, Id7, Id9, Id11) and their age-matched controls (Id6, Id8, Id10, Id12). In addition, blood DNA sample of a patient (HLRCC_N7) with germline fumarate hydratase (FH) mutation is included. Illumina paired-end sequencing for targeted libraries from Ly1, Ly2, Ly8, Ly9, Ly10 and Ly11 was done at Karolinska Institutet using 100 base-pair read length and the HiSeq2000 platform. Illumina paired-end sequencing for targeted libraries from Ly12, Ly13, Ly14, and DNMT3A mutation carriers and their age-matched controls was done as a service at BGI (BGI Tech Solutions Co., Ltd., China) using 126 base-pair read length and the HiSeq2500 platform.

  Dataset EGAD00001004785

• Reconstruction of complex rearrangement patterns causing the initiation of clear cell renal cell carcinoma.

  The genomic hallmark of clear cell renal cell carcinoma is the loss of the short arm of chromosome three. This appears to be the earliest genomic event in the formation of these cancers. Often chromosome 3 is lost at the same time as part of chromosome 5 is duplicated via an unbalanced translocation, often with features consistent with focal chromothripsis. In this study, we sought to reconstruct the chromothriptic event that underlies the initiation of kidney cancer. We used long read sequencing (promethION, Oxford Nanopore Technologies) of patient tumour-derived DNA to elucidate how a single cell division error can generate cancer genome complexity.

  Study EGAS00001004015

• Cell fate mapping of human glioblastoma reveals an invariant stem cell hierarchy pre- and post-treatment

  Human glioblastomas (GBMs) are thought to harbour a subpopulation of glioblastoma stem cells (GSCs) that initiate tumour formation and regrowth following treatment. However, the origin of their proliferative heterogeneity during tumour growth pre- and post-treatment remains poorly understood. Here we study the clonal evolution of DNA barcoded GBMs following their serial propagation in xenograft mouse models to define the fate behaviour of individual GBM cells. Through quantitative analysis of clone sizes scored across multiple passages, we show that the growth of GBM clones in vivo are consistent with a remarkably neutral process resulting from a conserved proliferative hierarchy. In this model, slow-cycling stem-like cells give rise to a more rapidly cycling progenitor population with extensive self-maintenance capacity, that in turn generates short-lived cells that lack proliferative ability. We also identify rare "outlier" clones that deviate from these dynamics, and further show that chemotherapy reproducibly facilitates the selective expansion of pre-existing drug-resistant GBM lineages. Finally, we show that coexisting, functionally distinct GSCs may be targeted separately with epigenetic compounds. These findings show that, independent of an evolving mutational signature, the clonal dynamics of human GBM can be surprisingly robust, with intratumoural heterogeneity derived primarily from the defined stochastic fate behaviour of tumour cells within a conserved proliferative hierarchy.

  Study EGAS00001002424

• DIAMOND PCR : plasma DNA LINE-1 targeted bisulfite sequencing, a new non-invasive multi-cancer detection marker

  The detection of circulating tumor DNA, which allows non-invasive tumor molecular profiling and disease follow-up, promises optimal and individualized management of patients with cancer. However, detecting small fractions of tumor DNA released when the tumor burden is reduced remains a challenge. We developed a PCR-based targeted bisulfite method coupled to deep sequencing to detect methylation patterns of L1PA elements,which we named DIAMOND (for Detection of Long Interspersed Nuclear Element Altered Methylation ON plasma DNA). We used sodium bisulfite chemical conversion to achieve base-pair resolution analysis and designed a multiplexed PCR based on 8 amplicons covering L1PAs .

  Dataset EGAD50000000646

• A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

  Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.

  Study EGAS00001005493

• Blood DNA Methylation in Post-Acute Sequelae of COVID-19 (PASC): a Prospective Cohort Study

  Background: DNA methylation integrates environmental signals with transcriptional programs. COVID-19 infection induces changes in the host methylome. While post-acute sequelae of COVID-19 (PASC) is a long-term complication of acute illness, its association with DNA methylation is unknown. No universal blood marker of PASC, superseding single organ dysfunctions, has yet been identified. Methods: In this single center prospective cohort study, PASC, post-COVID without PASC, and healthy participants were enrolled to investigate their symptoms association with peripheral blood DNA methylation data generated with state-of-the-art whole genome sequencing (WGS). PASC-induced quality-of-life deterioration was scored with a validated instrument, SF-36. Analyses were conducted to identify potential functional roles of differentially methylated loci, and machine learning algorithms were used to resolve PASC severity. Findings: 103 patients with PASC (22.3% male, 77.7% female), 15 patients with previous COVID-19 infection but no PASC (40.0% male, 60.0% female), and 27 healthy volunteers (48.1% male, 51.9% female) were enrolled. Whole genome methylation sequencing revealed 39 differentially methylated regions (DMRs) specific to PASC, each harboring an average of 15 consecutive positions, that differentiate patients with PASC from the two control groups. Motif analyses of PASC-regulated DMRs identify binding domains for transcription factors regulating circadian rhythm and others. Some DMRs annotated to protein coding genes were associated with changes of RNA expression. Machine learning support vector algorithm and random forest hierarchical clustering reveal 28 unique differentially methylated positions (DMPs) in the genome discriminating patients with better and worse quality of life.

  Study phs003658

• Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells

  Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm and the mitochondrial double membrane. Despite these physical barriers we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements and the features of the fusion fragments indicate that non-homologous end joining and/or replication-dependent DNA double strand break repair are the dominant mechanism involved. This study includes 12 pairs of whole-genome sequences (tumour and paired-normal), which present somatic mitochondrial DNA integrations in tumour genomes. Reference: Young Seok Ju et al., Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells, Genome Research (2015).

  Study EGAS00001001234

• Whole genome sequencing (bam files) of 5 samples of myxofibrosarcoma and 5 matched pairs

  Myxofibrosarcoma (MFS) is a rare subtype of sarcomas in the elderly, whose genetic basis is poorly understood. To elucidate it, the whole genome sequence was performed.

  Dataset EGAD00001007825

• Cancer Genetic Markers of Susceptibility (CGEMS) Breast Cancer Genome-wide Association Study (GWAS) - Primary Scan: Nurses' Health Study - Additional Cases: Nurses' Health Study 2

  The initial stage of the Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer genome-wide association study (GWAS) included genotyping 528,173 SNPs (Illumina HumanHap550) in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls from the Nurses' Health Study (NHS). Subsequently, incident invasive breast cancer cases from the Nurses' Health Study 2 (NHS2) cohort were genotyped using the Illumina HumanHap 610 quad. The NHS2 cases are younger than the cases in the first stage of the CGEMS breast cancer GWAS, which only included postmenopausal women. The NHS2 cases are a mix of pre- and postmenopausal women

  Study phs000147

• KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia

  NUP98 fusion oncoproteins (FOs) are a hallmark of childhood acute myeloid leukemia (AML). NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. Here we show that MYST family histone acetyltransferase (HAT) complex proteins including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1 associate with NUP98 FOs on chromatin and within condensates. MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of Kat6a and Kat7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with Menin inhibitor treatment, and was efficacious in Menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r AML.

  Study EGAS50000001075

• Dynamics of checkpoint receptors in γδ T cell subsets are associated with clinical responses during anti-PD-1 immunotherapies

  Gamma delta (γδ) T cells are innate-like lymphocytes with potent anti-tumor properties. Herein, we show that immune checkpoint receptors (ICRs) display differential expression and regulation by the JAK-STAT pathway in Vδ1 and Vδ2 cells and identify constitutive (e.g. TIGIT, PD-1) and inducible (e.g. TIM-3, LAG-3, CTLA-4) ICRs. In melanoma, all γδ T cell subsets downregulated AP-1 transcription factors, but Vδ1 cells specifically expressed high levels of ICR, TOX and inhibitory killer Ig-like receptor (KIR) transcripts, reminiscent of exhaustion. However, patient-derived cells were functionally competent, although induction of LAG-3 and CTLA-4 was impaired. During anti-PD-1 monotherapy, Vδ1 cells specifically bound high levels of therapeutic antibody but only in patients who responded to treatment, revealing a potential new prognostic marker for evaluating the efficacy of IC blockade (ICB) therapy. Finally, expression of KIR genes in Vδ1 cells was downregulated in response to successful ICB therapy. Collectively, our data indicate an intricate relationship between ICRs and γδ T cells and reveal novel approaches by which these cells can be harnessed in order to discern or improve cancer immunotherapy.

  Study EGAS50000001270

• Summary Statistics GWAS SSNS

  Column 1 rsid: SNP identifier;Column 2 chromosome: name of chromosome on which the SNP is located;Column 3: position: base pair position on the chromosome;Column 4 minor_test_allele: the base that constitutes the minor allele;Column 5 major_allele: the base that constitutes the major allele;Column 6 maf: the frequency of the minor allele, indicated as a fraction of 1;Column 7 allele_freq_cases: the minor allele frequency in cases;Column 8 allele_freq_controls: the minor allele frequency in controls;Column 9 regression_pvalue: the p-value for the difference in allele frequency between cases and controls;Column 10 odds_ratio: the odds ratio, as calculated using logistic regression under an additive model with adjustment for the first ten principal components of ancestry

  Dataset EGAD00010002316

• Summary Statistics GWAS SSNS

  Column 1 “rsid”: SNP identifier Column 2 “chromosome”: name of chromosome on which the SNP is located Column 3: “position”: base pair position on the chromosome Column 4 “minor_test_allele”: the base that constitutes the minor allele Column 5 “major_allele”: the base that constitutes the major allele Column 6 “maf”: the frequency of the minor allele, indicated as a fraction of 1 Column 7 “allele_freq_cases”: the minor allele frequency in cases Column 8 “allele_freq_controls”: the minor allele frequency in controls Column 9 “regression_pvalue”: the p-value for the difference in allele frequency between cases and controls Column 10 “odds_ratio”: the odds ratio, as calculated using logistic regression under an additive model with adjustment for the first ten principal components of ancestry

  Dataset EGAD00001008782

• Induction Failure in Childhood and Young Adult T-cell Acute Lymphoblastic Leukemia

  We carried out WGS and RNAseq on a cohort of 48 children and young adults with induction failure in T-cell Acute Lymphoblastic Leukemia (T-ALL) to identify genomic drivers of treatment resistance. The study includes WGS for 33 tumour/normal pairs and 15 tumour-only samples. In addition, there is RNAseq data for 37 cases.

  Dataset EGAD00001009058

• Reference Profiles of ExRNAs in Normal Human Pregnancy

  In this study, we did a comprehensive exRNA profiling of plasma and serum specimens from healthy pregnant women, sampled at different gestational time points, and including subjects with diverse geographical and ethnic backgrounds. This study also contains samples from male and female healthy donors to provide a baseline. The aim of this study is to identify miRNAs that can predict the gestation age and to build a miRNA profile across gestation using small RNA-seq data.

  Study phs003182

• Comparison Across Multiple Types of Sleep Deprivation

  This study is designed to assess neurobehavioral performance, as well as molecular and physiological changes associated with variations in timing and quantity of sleep. Gene expression changes associated with neurobehavioral (cognitive) performance were assessed in a time-series among individuals randomly assigned to four separate sleep conditions during a 10-day inpatient study: a well-rested control, sleep restriction with nighttime sleep, sleep restriction with daytime sleep to roughly simulate shiftwork schedules, and total (acute) sleep deprivation.

  Study phs003924

• Genomic Signatures of Intestinal Metaplasia in Six Countries with Varying Incidence of Stomach Cancer

  Intestinal metaplasia (IM) is a pre-cancerous condition associated with gastric cancer (GC), a deadly malignancy with varying geographic incidence. Performing a genomic analysis of over 1,500 IM samples from six countries, we identified 46 significantly mutated genes. We observed IM driver genes associated with high-risk populations and worse prognosis (ARID1A), members of the KRAS/MAPK signalling pathway (KRAS, BRAF, MAP2K1, MAP3K1, MAP2K4, NF1), and altered mucosal immunity (PIGR).

  Study EGAS50000001056

• Tenk10k Phase 1: Genotypes

  TenK10K Phase 1 is a dataset of matched human whole-genome sequencing (WGS) from 1,925 individuals, and single-cell RNA sequencing (scRNA-seq) from over 5 million peripheral blood mononuclear cells across 28 immune cell types. Single-cell ATAC sequencing was additionally performed on a subset of 922 individuals. This EGA study consists of the WGS data from 1,925 individuals while a separate EGA study comprises the scRNA-seq and scATAC-seq data.

  Study EGAS50000001654

• Gut Microbiome and Types of Colorectal Polyps

  Colorectal cancer is a heterogeneous disease arising from at least two precursors-the conventional adenoma and the serrated polyp. This dataset was used to test the relationship of the gut microbiota to specific colorectal polyp types. We included samples from two independent study populations based at colonoscopy clinics: the Centers for Disease Control and Prevention (CDC) Study of In-home Tests for Colorectal Cancer (SIT), and the New York University (NYU) Human Microbiome and Colorectal Tumor study. Gut microbiota were assessed in 667 colonoscopy-screened adults by 16S rRNA gene sequencing of stool samples, of which 540 were included in our analysis. Participants were categorized as conventional adenoma cases, serrated polyp cases, or polyp-free controls. CA cases were further classified as proximal or distal and as non-advanced or advanced. Serrated polyp cases were further classified as hyperplastic polyp or sessile serrated adenoma. Our results show associations between gut microbiome composition and presence of conventional adenomas, including reduced diversity and alterations in taxon abundance.

  Study phs001381

• HSC_colony_many_years_post_allogeneic_bone_marrow_transplant_TGS

  This study looks at human donors and recipients of allogeneic blood & marrow marrow transplantation. Each transplant "pair" (donor & recipient) underwent the transplant procedure 10 -30 years prior to sampling - the majority for an underlying diagnosis of leukemia. We will perform whole-genome sequencing on tens to hundreds of single HSPC (haematopoietic stem and progenitor cell)-derived colonies per individual. We will infer the phylogeny of these cells (those from both donor & recipient within a pair) by analysing the somatically acquired mutations within each cell. The structure of the phylogeny will allow estimates of hitherto unknown parameters such as the number of HSCs that engraft long-term, the dynamics of the engraftment process on the HSC level, and the additional mutation burden acquired through the arduous transplant procedure. This TGS part of the study is used for assessing the contribution of clones to mature blood subsets, and better timing mutations relative to transplantation.

  Study EGAS00001005298

• HSC_colony_many_years_post_allogeneic_bone_marrow_transplant___Bait_set_2

  This study looks at human donors and recipients of allogeneic blood & marrow marrow transplantation. Each transplant "pair" (donor & recipient) underwent the transplant procedure 10 -30 years prior to sampling - the majority for an underlying diagnosis of leukemia. We will perform whole-genome sequencing on tens to hundreds of single HSPC (haematopoietic stem and progenitor cell)-derived colonies per individual. We will infer the phylogeny of these cells (those from both donor & recipient within a pair) by analysing the somatically acquired mutations within each cell. The structure of the phylogeny will allow estimates of hitherto unknown parameters such as the number of HSCs that engraft long-term, the dynamics of the engraftment process on the HSC level, and the additional mutation burden acquired through the arduous transplant procedure. This TGS part of the study is used for assessing the contribution of clones to mature blood subsets, and better timing mutations relative to transplantation.

  Study EGAS00001005534

• The European MAPPYACTS trial: Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies

  MAPPYACTS (NCT02613962) is an international prospective precision medicine trial aiming to define tumor molecular profiles in pediatric patients with recurrent/refractory malignancies, in order to suggest the most adapted salvage treatment. From February 2016 to July 2020, 787 patients were included in France, Italy, Ireland and Spain. At least one genetic alteration leading to targeted treatment suggestion was identified in 436 patients (69%) with successful sequencing; 10% of these were considered "ready for routine use". Of 356 patients with follow-up beyond 12 months, 107 (30%) received one or more matched targeted therapies, 56% of them within early clinical trials, mainly in the AcSé-ESMART platform trial (NCT02813135). Overall, matched treatment resulted in a 17% objective response rate, those of patients with "ready for routine use" alterations was 38%. In patients with extra-cerebral tumors, 76% of actionable alterations detected in tumor tissue were also identified in circulating cell free DNA (cfDNA).

  Study EGAS00001005935

• HSC_colony_many_years_post_allogeneic_bone_marrow_transplant___Bait_set_3

  This study looks at human donors and recipients of allogeneic blood & marrow marrow transplantation. Each transplant "pair" (donor & recipient) underwent the transplant procedure 10 -30 years prior to sampling - the majority for an underlying diagnosis of leukemia. We will perform whole-genome sequencing on tens to hundreds of single HSPC (haematopoietic stem and progenitor cell)-derived colonies per individual. We will infer the phylogeny of these cells (those from both donor & recipient within a pair) by analysing the somatically acquired mutations within each cell. The structure of the phylogeny will allow estimates of hitherto unknown parameters such as the number of HSCs that engraft long-term, the dynamics of the engraftment process on the HSC level, and the additional mutation burden acquired through the arduous transplant procedure. This TGS part of the study is used for assessing the contribution of clones to mature blood subsets, and better timing mutations relative to transplantation.

  Study EGAS00001006572

• The patterns and dynamics of genomic instability in metastatic pancreatic cancer

  Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97–98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2–M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.

  Study EGAS00000000064

• Somatic Mutations and Cell Lineage in the Human Brain

  Genetic mutations causing human disease are conventionally thought to be inherited from one's parents and present in all somatic (body) cells. Increasingly however, somatic mutations are implicated in neurological diseases. Somatic mutations that arise during the cell divisions of prenatal brain development are inherited in clonal fashion and can cause neurodevelopmental diseases, even when present at low levels of mosaicism. In this study we use whole genome, RNA, and ATAC sequencing of single cells and bulk tissue to identify somatic mutations in control, and some disease, brains to: 1) identify and catalogue the mutations which shape the somatic neuronal genome; 2) perform a cell lineage analysis of the human brain using clonal somatic mutations in cortical neurons; 3) determine patterns of somatic mutations at different ages and in aging related disease phenotypes; and 4) relate cell lineage patterns to cell phenotype in the human brain through cell type-specific analyses.

  Study phs001485

• Amplicon_based_sequencing_of_drug_resistant_organoids

  A BRAF V600E colorectal organoid which is sensitive to MAP kinase inhibition was mutagenised with the chemical mutagen ENU and then drug selected using a combination of Trametinib, Dabrafenib and Cetuximab. Single cell derived organoids were then manually picked and expanded in drug. Resistance was confirmed in a 14 day assay and DNA was collected. These then underwent targeted amplicon-based sequencing to confirm candidate resistance effectors from a screen in 2 2D BRAF V600E colorectal cell lines. Pools of resistant clones were also sequenced.

  Study EGAS00001001639

• H3Africa - An integrated approach to the identification of genetic determinants of susceptibility to trypanosomiasis

  The objective of the TrypanoGEN project is to discover genetic variants associated with different responses to sleeping sickness infection. The project was designed in two phases:Phase 1) Variant discovery; 222 samples were sequenced to approximately 10X coverage on an Illumina 2500 with 2x150bp reads, at the University of Liverpool Center for Genomic Research. In addition, 77 samples from Cameroon and Zambia were sequenced to approximately 30X Coverage at Baylor College of Medicine. The sequenced reads were mapped onto the 1000 genomes project human_g1k_v37_decoy reference genome using BWA. The SNP calling on all the samples was done using the genome analysis tool kit GATK v3.4. Samples were selected from seven populations where Trypanosomiasis is endemic: Nilo-Saharan speakers from North-West Uganda and Niger-Congo speakers from South-East Uganda, DRC, Ivory Coast, Guinea, Cameroon and Zambia. The samples included 182 controls, 97 cases, 17 latent infections and 3 suspect cases. Phase 2) Variants discovered in Phase 1 will be used in the development of the H3Africa SNP chip. This chip will then be used in a GWAS study to identify variants associated with trypanosomiasis.

  Study EGAS00001002602

• Institut Curie Neuroblastoma Whole Genome Sequencing Diagnosis Relapse

  Neuroblastoma, a clinically heterogeneous pediatric cancer, is characterized by distinct genomic profiles but few recurrent mutations. As neuroblastoma is expected to have high degree of genetic heterogeneity, study of neuroblastoma's clonal evolution with deep coverage whole-genome sequencing of diagnosis and relapse samples will lead to a better understanding of the molecular events associated with relapse. Samples were included in this study if sufficient DNA from constitutional, diagnosis and relapse tumors was available for WGS. Whole genome sequencing was performed on trios (constitutional, diagnose and relapse DNA) from eight patients using Illumina Hi-seq2500 leading to paired-ends (PE) 90x90 for 6 of them and 100x100 for two. Expected coverage for sample NB0175 100x100bp was 30X for tumor and constitutional samples. For the seven other patients expected coverage was 80X for tumor samples with PE 100x100, 100X in the other tumor samples and 50X for all constitutional samples (see table 1). Following alignment with BWA (Li et al., Oxford J, 2009 Jul) allowing up to 4% of mismatches, bam files were cleaned up according to the Genome Analysis Toolkit (GATK) recommendations (Van der Auwera et al., Current Protocols in Bioinformatics, 2013, picard-1.45, GenomeAnalysisTK-2.2-16). Variant calling was performed in parallel using 3 variant callers: GenomeAnalysisTK-2.2-16, Samtools-0.1.18 and MuTect-1.1.4 (McKenna et al., Genome Res, 2010; Li et al., Oxford J, 2009 Aug; Cibulskis et al., Nature, 2013). Annovar-v2012-10-23 with cosmic-v64 and dbsnp-v137 were used for the annotation and RefSeq for the structural annotation. For GATK and Samtools, single nucleotide variants (SNVs) with a quality under 30, a depth of coverage under 6 or with less than 2 reads supporting the variant were filter out. MuTect with parameters following GATK and Samtools thresholds have been used to filter our irrelevant variants. .SNVs within and around exons of coding genes overlapping splice sites.. Then,variants reported in more than 1% of the population in the 1000 genomes (1000gAprl_2012) or Exome Sequencing Project (ESP6500) have been discarded in order to filter polymorphisms. Finally, synonymous variants were filtered out. MuTect focuses on somatic by filtering with constitutional sample. Mpileup comparison between constitutional and somatic DNAs allowed us to focus also on tumor specific SNVs with GATK and Samtools. Finally, every SNV called by our pipeline and also supported in any constitutional samples were filtered our in order to prevent putative constitutional DNA coverage deficiency. Then we analyzed CNVs (copy number variants) with HMMcopy-v0.1.1 (Gavin et al., Genome Res, 2012) and control-FREEC-v6.7 (Boeva et al., Bioinformatics 2011) with a respective window of 2000bp and 1000 bp, and auto-correction of normal contamination of tumor samples for Control-FREEC. Finally we explored Structural variants (SVs) including deletions, inversions, tandem duplications and translocations using DELLY-v0.5.5 with standard parameters (Rausch et al., Oxford J, 2012). In tumors, at least 10 supporting reads were required to make a call and 5 supporting reads for the sample NB0175 with a coverage of only 40X (see table 2). To predict SVs in constitutional samples for subsequent somatic filtering, only 2 supporting reads were required in order not to miss one. To identify somatic events, all the SVs in each normal sample were first flanked by 500 bp in both directions and any SVs called in a tumor sample which was in the combined flanked regions of respective normal sample was removed (see graph 1). Deletions with more than 5 genes impacted or larger than 1Mb and inversions or tandem duplications covering more than 4 genes, were removed. We focused on exonic and splicing events for deletions, inversions, and tandem duplications. For translocation, we keep all SVs that occurred in intronic, exonic, 5'UTR, upstream or splicing regions. Bioinformatics detection of variations with Deep sequencing approach Once PE reads merged and adaptors trimmed by SeqPrep with default parameters, merged reads were aligned via the BWA (Li H. and Durbin R. 2009 PMID 19451168) allowing up to 1 differences in the 22-base-long seeds and reporting only unique alignments. Only reads having a mapping quality 20 or more have been further analysed. Variant calling software was not used, since we aimed to predict variations at low frequencies, observed in less than 1% of reads. Such variants require a custom approach. Using DepthOfCoverage functions of the Genome Analysis Toolkit (GATK) v2.13.2 (McKenna A, et al., 2010 Genome Research PMID: 20644199), we focused on high quality coverage of bases A, C, G and T at the targeted variant position. Depth of coverage of each base following a mapping quality higher than 20 and a base quality higher than 10 have been taken into account in order to focus only on high quality data. Aiming to determine the background level of variability at the studied regions, 10 control samples were included in the analysis. The same approach and filtering criteria have been applied as introduced above over the entire amplicons. In order to highlight variants, for each sample the frequencies of each bases at each amplicon position were then compared to those observed in the set of controls. Statistical analyses were performed with the R statistical software (http://www.R-project.org). Fisher’s exact two-sided tests with a Bonferroni correction were performed to compare percentages of bases between the data sets, i.e. for a given base between a case and the controls. Finally, significant variations were filtered-in once (i) a significant increase in the percentage of avariant base and (ii) a significant decrease in the percentage of it's reference base following our p.values criteria was observed (p.val < 0.05).

  Dataset EGAD00001001356

• Germ Cell Tumor Molecular Heterogeneity Revealed through Analysis of Primary and Metastasis Pairs

  Purpose: While primary germ cell tumors (GCTs) have been extensively characterized, molecular analysis of metastatic sites has been limited. We performed whole-exome sequencing and targeted next-generation sequencing on paired primary and metastatic GCT samples in a patient cohort enriched for cisplatin-resistant disease. Experimental Design: Tissue sequencing was performed on 100 tumor specimens from 50 patients with metastatic GCT, and sequencing of plasma cell-free DNA (cfDNA) was performed for a subset of patients. Data is being provided for a subset of 10 patients whose samples were analyzed using whole-exome sequencing. Results: The mutational landscape of primary and metastatic pairs from GCT patients was highly discordant (68% of all somatic mutations were discordant). Whereas genome duplication was common and highly concordant between primary and metastatic samples, only 25% of primary-metastasis pairs had =50% concordance at the level of DNA copy number alterations (CNAs). Evolutionary-based analyses revealed that most mutations arose after CNAs at the respective loci in both primary and metastatic samples, with oncogenic mutations enriched in the set of early occurring mutations versus variants of unknown significance (VUS). TP53 pathway alterations were identified in nine cisplatin-resistant cases and had the highest degree of concordance in primary and metastatic specimens, consistent with their association with this treatment-resistant phenotype. Conclusions: Analysis of paired primary and metastatic GCT specimens revealed significant molecular heterogeneity for both CNAs and somatic mutations. Among loci demonstrating serial genetic evolution, most somatic mutations arose after CNAs but oncogenic mutations were enriched in the set of early occurring mutations as compared to VUS. Alterations in TP53 were clonal when present and shared among primary-metastasis pairs. Reprinted from pending publication, with permission from JCO Precision Oncology.

  Study phs002229

• Genome-Wide Association Study of Breast Cancer in the African Diaspora - the ROOT study

  The paucity of data on the genetic epidemiology of breast cancer for racial/ethnic groups other than those of European ancestry hinders the development of innovative interventions to reduce health disparities. Women in the African Diaspora experience a disproportionate burden of pre-menopausal breast cancer in comparison to all other races for reasons that remain unknown and understudied. This higher proportion of early-onset breast cancer might suggest a stronger genetic component in these populations. Genome-wide association studies (GWAS) have revealed several genetic loci that confer risk of breast cancer. Because all GWAS started the discovery stage in women of European ancestry and replicated mainly in women of European ancestry, we propose a novel approach for a GWAS in indigenous African women to identify alleles associated with breast cancer risk which will then be replicated in other populations. This innovative design builds on our current understanding of the etiologic heterogeneity in breast cancer and the distribution of breast cancer molecular subtypes which differ between women of African ancestry and women of European ancestry. The major objective of the proposed studies is to get to the "root" causes of breast cancer by identifying breast cancer risk alleles in a pooled sample of women of African ancestry and to replicate our findings in other populations. To achieve this objective, we conducted a case control study of breast cancer in women of African ancestry, including Africans living in Nigeria, African Americans and African Barbadians. We will genotype ~3800 individuals using the Illumina HumanOmni2.5-Quad platform. We will conduct both standard and novel genetic analyses of the data to map genes associated with breast cancer susceptibility, verify genotyping and carry out fine-mapping studies in genes or regions showing association with breast cancer risk, and replicate in other African American and non-African American populations. By pooling unique resources from studies throughout the African Diaspora, this study has the potential to identify risk alleles in several genes that contribute to increased breast cancer risk and may have implications for early detection, prognosis and treatment of breast cancer in ALL women. This should ultimately lead to improved outcomes for those who suffer a disproportionate burden of early-onset breast cancer.

  Study phs000383

• Metastatic Adult Pancreatoblastoma: Multimodal Treatment and Molecular Characterization of a Very Rare Disease (NCT MASTER)

  Pancreatoblastoma is a rare malignant tumor that occurs predominantly in children. We identified four adult patients with metastasizing pancreatoblastoma at a high-volume German university cancer center which were treated with multimodal therapies between 2013 and 2018. In three cases, we performed a comprehensive molecular analysis that included whole-genome sequencing (WGS) or whole-exome sequencing (WES); transcriptome sequencing was performed in two cases, respectively. Subsequent recommendations of molecularly stratified treatment options were discussed within a dedicated molecular tumor board (MTB) embedded in a precision oncology program (NCT MASTER).

  Study EGAS00001004157

• Whole Tumor spatial heterogeneity in metastatic melanoma

  Heterogeneous inter-tumoral responses, sustained periods of apparent clinical benefit despite lack of objective response to various therapies, and even spontaneous remission are well known within a subpopulation of advanced melanoma patients. The molecular and cellular dynamics facilitating long-term survival remain poorly defined, particularly in the current era ofexposure to multiple potentially active therapies. We studied an exceptional case of long-term survival in a patient with non-responding metastatic melanoma in order to characterize the clonal and microenvironmental factors.We performed immunogenomic analysis of 3 metachronous tumors, and of 67 intratumor sub-regions of one metastatic lesion, usingwhole exome sequencing, RNA-sequencing, immunohistochemistry, and T cell receptor sequencing. Longitudinal analysesidentified mutations in severalknownresistance genes affecting distinctmetastases. Intra-tumoral immune signatures revealed spatially-distinct pockets of immune activation and suppression throughout the metastasis. A specific T cell VBeta CDR3 rearrangement was identified as both dominant and recurrent not only across multiple spatial points within a single tumor mass, but also across metachronous tumors spanning the patient’s disease course. Immunophenotyping of this T cell population with single-cell sequencingsuggestedrepeatedT-cell priming events leading to the persistence of both activated and exhausted T cells bearing this same TCR-Beta at any given time.Our findings highlight genomic and immune heterogeneityin metastatic disease, extending to the intra-tumoral leveland provide a rationale for integrative spatiotemporal analysis of metastatic lesions in the context of immune checkpoint blockade.

  Study EGAS00001003292

• 2018_ETO_WGS

  This study includes 12 paired samples of Korean AML-ETO paitients.12 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.

  Study EGAS00001002804

• 2015_AML_ETO

  This study includes 10 paired samples of 2015 Korean AML-ETO paitients.10 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.

  Study EGAS00001002897

• 2015_AML_ETO_WGS_additional

  This study includes 2 paired samples of 2015 Korean AML-ETO paitients. 2 AML-ETO tumor samples are paired with each normal(Saliva or BM derived) sequencing data.The results of this WGS study were analyzed by Mutect and GATK for ranking germline variants and cancer variants to make mutational profile matrix.

  Study EGAS00001002898

• A distinct monocyte cellular state links systemic immune dysregulation to pulmonary impairment in long COVID

  Long COVID is a debilitating disease with a very heterogeneous disease aetiology. In this study, we collected blood from Long COVID patients and generated single-cell multiomics datasets. The samples collected were both longitudinal and cross-sectional cohorts. The aim of the study involved examining the transcriptomic and epigenetic landscape of circulating immune cells from these samples to better understand the disease imprints.

  Study EGAS50000001215

• Circulating Tumor DNA Analysis Profiles of Repotrectinib in NTRK fusion–positive advanced solid tumors: a phase 1/2 trial

  The dataset contains circulating tumor DNA (ctDNA) profiles from frozen plasma samples of 593 patients from the TRIDENT-1 clinical trial. Plasma was processed with centrifugation and automated liquid handling systems, and cell-free DNA was extracted using the Qiagen QIAsymphony platform. ctDNA libraries were constructed with the Guardant360 2.11 assay, which used targeted, hybridization-based capture and barcoding of cfDNA fragments for digital analysis, followed by high-throughput sequencing on the Illumina NextSeq 550 instrument. Sequencing data were processed and interpreted using the Bioinformatics Pipeline (BIP v3.5.2 or later) for variant calling and quantification and managed within LabVantage LIMS (v3.7 or later) to support sample tracking and workflow integration. Aligned read files are provided in bam and bai formats.

  Dataset EGAD50000002249

• Whole genome and transcriptome sequencing of cancer of unknown primary tumours

  Whole genome and transcriptome sequencing of cancer of unknown primary tumours was used to determine yield of clinical biomarkers for a molecular guided trial or for resolving cancer type of origin. This study includes profiling of germline DNA and tumour DNA and RNA by whole genome and transcriptome sequencing. All samples are in BAM format aligned with GRCh38 reference genome. This dataset includes: 1. Whole genome sequencing (WGS) of 78 cancer of unknown primary tumour samples and 73 matched germline DNA. 2. Whole transcriptome sequencing (WTS) of 69 cancer of unknown primary tumour samples (matched to WGS cases) 3. Whole genome sequencing of 22 cell-free DNA samples from cancer of unknown primary patients and matched Germaine DNA(8 samples matched to tumour WGS)

  Dataset EGAD50000000656

• Dataset for study Genome-wide gene expression analysis following CRISPRi of transposable elements

  Transposable elements (TEs), once regarded as parasitic genomic remnants, are now recognized as key regulators of gene expression and genome evolution, yet the functional specificity of individual TE subfamilies remains largely unexplored. This dataset investigates the transcriptional consequences of targeted repression of MER57E3 and LTR10B2 elements using CRISPR interference (CRISPRi) in human induced pluripotent stem cells (hiPSCs). hiPSCs expressing CRISPRi machinery (n = 2 biological replicates) were transduced with guide RNAs targeting individual or grouped copies of MER57E3 and LTR10B2, as well as the ZNF678 promoter or a lacZ non-targeting control. Transduced cells were subsequently differentiated into neural progenitor cells (NPCs), and total RNA was extracted for mRNA library preparation and sequencing. The dataset comprises 24 single-end mRNA-seq FASTQ files generated from these NPCs and wild-type controls.

  Dataset EGAD00001015689

• Genetic coupling of enhancer activity and connectivity in gene expression control

  In this study, we investigated whether the genetic effects of eQTLs on enhancer activity and enhancer-promoter contacts (connectivity) are inherently coupled or distinct. To address this, we performed Capture Hi-C targeting ~1100 eQTL loci, along with ATAC-seq and RNA-seq, in monocytes from 34 healthy male donors. Using single-modality and multi-modality Bayesian statistical approaches, we demonstrated that eQTL effects are predominantly shared across enhancer activity, connectivity, and gene expression. However, we also identified a locus where an eQTL disrupts a CTCF binding site at a putative insulator, facilitating contacts between the PCK2 gene promoter and downstream enhancers. To validate these findings, we used 4C-seq to confirm the allelic effects of eQTLs on enhancer-promoter connectivity at the PCK2 locus and another eQTL region associated with THBS1 expression, both of which showed consistent eQTL effects across all three modalities. Additionally, we conducted Hi-C on monocytes from two donors to map reference TADs and performed ChIP-seq to confirm the allelic effects of the PCK2 eQTL on CTCF binding. Together, these data provide comprehensive insights into the genetic coupling of enhancer activity, connectivity, and gene expression.

  Study EGAS50000000756

• Massively parallel nanowell-based single-cell gene expression profiling

  Technological advances have enabled transcriptome characterization of cell types at the single-cell level providing new biological insights. New methods that enable simple yet high-throughput single-cell expression profiling are highly desirable. Here we report a novel nanowell-based single-cell RNA sequencing system, ICELL8, which enables processing of thousands of cells per sample. The system employs a 5184-nanowell-containing microchip to capture ~1300 single cells and process them. Each nanowell contains preprinted oligonucleotides encoding poly-d(T), a unique well barcode, and a unique molecular identifier. The ICELL8 system uses imaging software to identify nanowells containing viable single cells and only wells with single cells are processed into sequencing libraries. Here, we report the performance and utility of ICELL8 using samples of increasing complexity from cultured cells to mouse solid tissue samples. Our assessment of the system to discriminate between mixed human and mouse cells showed that ICELL8 has a low cell multiplet rate (< 3%) and low cross-cell contamination. We characterized single-cell transcriptomes of more than a thousand cultured human and mouse cells as well as 468 mouse pancreatic islets cells. We were able to identify distinct cell types in pancreatic islets, including alpha, beta, delta and gamma cells. Overall, ICELL8 provides efficient and cost-effective single-cell expression profiling of thousands of cells, allowing researchers to decipher single-cell transcriptomes within complex biological samples.

  Study EGAS00001002320

• Whole-genome and transcriptome versus panel sequencing in precision oncology: A translational-clinical comparison

  Precision oncology offers new cancer treatment options. While the use of whole-genome (WGS) and transcriptome (TS) sequencing remains often confined to specific clinical programs, molecular analysis with gene panels is more common clinical practice. Methods: Twenty patients with rare or advanced tumors sequenced by WGS/TS within the DKFZ/NCT/DKTK-MASTER program from 2015 to 2020 (MASTER 1) were additionally sequenced with the TSO500 DNA and TST170 RNA Assay by Illumina. Original Molecular Tumor Board (MTB) therapy recommendations (TR) were juxtaposed with TR from NGS panel data analysis (comparison 1). To mitigate temporal differences between the two sequencings, WGS/TS was bioinformatically reanalyzed (MASTER 2), and new TR were again compared (comparison 2). Results: In comparison 1, 47.1% of the MASTER 1’s TR and 62.8% of the panel’s TR were identical, as were 45.9% of the TR of MASTER 2 and 54.9% of the panel in comparison 2. In both MASTER 1 and MASTER 2, 26.5% and 36.1% of TR, respectively, relied on Biomarkers (BM) which were not covered by the panel. Eight of the ten MTB-derived therapy implementations were also supported in the panel, the two remaining ones being based on BM absent from the panel. Conclusions: About half of the TR in WGS/TS and panel sequencing were identical. Around a third of TR issued by WGS/TS were based on BM which are not covered by the panel, leading to therapy implementations. The presented data underscores the clinical value of comprehensive molecular analyses in individuals with advanced cancers.

  Study EGAS50000000431

• RNA-sequençing of 21 inflammatory hepatocellular adenomas

  The French ICGC project on liver tumors is coordinated by Pr Jessica Zucman-Rossi and funded by Inca (French Institute for Cancer). The aim of the present project is to identify the catalog of somatic and germline mutations in liver tumors.The present series corresponds to 21 RNA-seq of IHCA samples. Aligned bam files correspond to hg38 human reference.

  Study EGAS00001003685

• Washington University PDX Development and Trial Center

  This data set is a collection of patient specimens from common and rare cancers that have been developed into patient-derived xenograft (PDX) models at the Washington University PDX Development and Trial Center (WU-PDTC). The goal of the PDTC is to develop and characterize PDX models, gaining insight into tumor biology, and validating biomarkers across all major tumor types. Pre-clinical experiments in these PDX models will be used to advance our ability to predict clinical responses to new molecularly targeted agents under development.

  Study phs002305

• Transcriptome and epigenomic landscape of cytotrophoblasts from normal and HDP placentas

  Hypertensive isorders of pregnancy (HDP) is a severe pregnancy-related disorder that poses significant risks to both maternal and fetal health. Dysfunctional placental development is one of the major contributors to the onset of HDP. In this study, we investigated the gene expression and epigenomic modifications in cytotrophoblasts from normal and HDP placentas. The information obtained in this study contributes to the growing body of knowledge aimed at improving the diagnosis, management, and treatment of HDP.

  Study JGAS000667

• PEVOsq

  The PEVOData PEVOsq basket trial is an open-label, multi-center, phase II trial investigating the combination of pembrolizumab (an immune checkpoint inhibitor) with vorinostat (a histone deacetylase inhibitor). This trial focuses on treating patients with recurrent or metastatic squamous carcinomas, including cancers of the cervix, head and neck, anus, vulva/vagina, penis, and lung. The aim is to evaluate the efficacy and safety of this combination, with pembrolizumab administered every 3 weeks and vorinostat daily. Outcomes include overall response rate and progression-free survival.

  Study EGAS50000000731

• TRACERx 100: RNAseq data from the first 100 TRACERx tumours

  TRACERx (TRAcking Cancer Evolution through therapy (Rx)) is a prospective cohort study designed to investigate intratumor heterogeneity (ITH) in relation to clinical outcome, and to determine the clonal nature of driver events and evolutionary processes in early stage non-small cell lung cancer (NSCLC). This study looks at the multi-region RNAseq data from the TRACERx100 cohort with high enough quality RNA available. There is RNAseq data from 164 regions (64 patients).

  Study EGAS00001003458

• The long term effects of chemotherapy on normal blood - WGS dataset

  In developed countries, ~10% of individuals are exposed to systemic chemotherapy for cancer and other diseases. Many chemotherapeutic agents act by increasing DNA damage in cancer cells, hence triggering cell death. However, there is limited understanding of the extent and consequences of collateral DNA damage to normal tissues. To investigate the impact of chemotherapy on mutation burdens and cell population structure of a normal tissue we sequenced blood cell genomes from 23 individuals, aged 3-80 years, treated with a range of chemotherapy regimens. Substantial additional mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but there were differences in burden between different classes of agent, different agents of the same class and different blood cell types. Chemotherapy also induced premature changes in the cell population structure of normal blood, similar to those of normal ageing. The results constitute an initial survey of the long-term biological consequences of cytotoxic agents to which a substantial fraction of the population is exposed during the course of their disease management, raising mechanistic questions and highlighting opportunities for mitigation of adverse effects.

  Dataset EGAD00001015339

• CRISPR iPSC methods paper

  This submission is of the sequencing data used in the CRISPR iPSC methods paper. Specifically it is 3 fastq files that each represent a replicate of an experiment to transduce the Toronto KnockOut CRISPR Library - Version 3 (TKOv3) into inferred pluripotent stem cell (iPSC) derived macrophages. The sequencing is of the guide RNAs from the TKOv3 having been extracted from the transduced iPSC derived macrophages.

  Dataset EGAD00001007020

• Epigenomics of Human CD8 T cell Differentiation and Aging

  The efficacy of the adaptive immune response declines dramatically with age, but the cell-intrinsic mechanisms driving the changes characteristic of immune aging in humans remain poorly understood. One hallmark of immune aging is the loss of self-renewing naive cells and the accumulation of differentiated but dysfunctional cells within the CD8 T cell compartment. Using ATAC-seq, we first inferred the transcription factor binding activities that maintain the naive and central and effector memory CD8 T cell states in young adults. Integrating our results with RNA-seq, we determined that BATF, ETS1, Eomes, and Sp1 govern transcription networks associated with specific CD8 T cell subset properties, including activation and proliferative potential. Extending our analysis to aged humans, we found that the differences between memory and naive CD8 T cells were largely preserved across age, but that naive and central memory cells from older individuals exhibited a shift toward a more differentiated pattern of chromatin openness. Additionally, aged naive cells displayed a loss in chromatin openness at gene promoters, a phenomenon that appears to be due largely to a loss in binding by NRF1, leading to a marked drop-off in the ability of the naive cell to initiate transcription of mitochondrial genes. Our findings identify BATF- and NRF1-driven gene regulation as targets for delaying CD8 T cell aging and restoring T cell function.

  Study phs001187

• San Francisco Bay Area Latina Breast Cancer Study

  The genome-wide association study (GWAS) includes participants enrolled into two different studies. The first study, the San Francisco Bay Area Cancer Study (SFBCS) is a population-based case-control study of breast cancer conducted in the San Francisco Bay Area and included women ages 35-79 years from three racial/ethnic groups: Non-Hispanic whites, African Americans, and Hispanics/Latinas. For the GWAS, only Hispanic/Latina women were included. Women diagnosed with invasive breast cancer between 1995 and 2002 were identified through the Greater Bay Area Cancer Registry. Controls were identified by random digit dialing and were frequency-matched to cases by age in 5 year increments and by race/ethnicity. Hispanic/Latina ethnicity was assessed by self-report. 175 Hispanic/Latina cases and 307 Hispanic/Latina controls from the SFBCS had given adequate consent and provided biospecimens that were used in the GWAS to be included in this data submission. The second study is the Northern California site of the Breast Cancer Family Registry (NC-BCFR). This population-based family study recruited breast cancer cases ages 18-64 years diagnosed from 1995-2009 that were identified through the Greater Bay Area Cancer Registry. Cases included all women at increased genetic susceptibility for breast cancer who met one or more of the following criteria: (a) being diagnosed with breast cancer at age <35 years; b) having a personal history of ovarian cancer or childhood cancer; (c) being diagnosed with two different breast cancers (bilateral breast cancers), with the first one diagnosed at age <50 years; and d) having one or more first-degree relatives with breast cancer, ovarian cancer or childhood cancer. Cases not meeting these criteria were randomly sampled and racial/ethnic minorities were oversampled. Controls were recruited by random digit dialing and were matched by 5-year age increments and by race/ethnicity. For the current GWAS only Latina/Hispanic cases and controls were included. Latina/Hispanic ethnicity was assessed by self-report. 631 Hispanic/Latina cases and 61 Hispanic/Latina controls from the NC-BCFR had given adequate consent and provided biospecimens that were used in the GWAS to be included in this data submission.

  Study phs000912

• ENCORAFENIB COMBINED WITH BINIMETINIB FOR BRAFV600E-MUTATED RELAPSED/REFRACTORY MULTIPLE MYELOMA: THE PHASE II GMMG-BIRMA TRIAL (Hipo_K08K)

  Activating BRAF mutations are rare events in multiple myeloma but have been shown to be promising therapeutic targets in small case studies. This multicenter phase II trial assessed the efficacy and safety of the BRAF/MEK inhibitors, encorafenib and binimetinib, in patients with relapsed/refractory multiple myeloma (RRMM) carrying an activating BRAFV600E mutation. Twelve RRMM patients with a median of five prior lines of therapy were enrolled. The study met its primary endpoint with 10 patients achieving at least a partial response according to IMWG criteria (overall response rate 83.3%). Responses occurred rapidly within the first cycle and deepened over time. The median progression-free survival (PFS) was 5.6 months and overall survival was 55% at 24 months. Genomic profiling revealed RAS mutations and structural variants involving the BRAF locus to be drivers of resistance to BRAF/MEK inhibition in RRMM. This trial demonstrates the value of translationally driven clinical trials in selected patient populations.

  Study EGAS00001005973

• RNAseq dataset of ovarian cancer patients

  Dataset of transcriptomics data from a cohort of individuals diagnosed with ovarian cancer. This dataset includes RNAseq sequencing data from 68 individuals. A total of 109 tumor samples were sequenced. Samples were prepared with the Illumina TruSeq Stranded RNA library. Sequencing data are paired end.

  Dataset EGAD50000001556

• Whole exome sequencing of pediatric soft tissue sarcoma PDX models

  Childhood cancer remains one of the leading causes of death in pediatric patients in Europe. Pediatric sarcomas, comprising soft tissue sarcomas and malignant bone tumors, are a heterogenous group of malignancies, with more than 50 subtypes (WHO classification). Due to low case numbers, studying pediatric sarcomas requires accurate and reliable preclinical models. Here, we established 18 soft tissues sarcoma PDX models, including Ewing Sarcoma, Rhabdmyosarcoma and Osteosarcoma. We characterized these models by Whole Exome Sequencing and assessd the response to a wide range of drugs.

  Study EGAS50000000048

• Single cell atlas of relapsed/refractory large B-cell lymphoma

  Relapsed/refractory large B-cell lymphomas (rrLBCL) are clinically and biologically diverse lymphoid malignancies with intricate microenvironments that play a key role in disease development. In this study, we used single-nucleus multiome profiling along with bulk DNA and RNA sequencing on 120 tumor and control biopsies to comprehensively characterize the various cell types and subsets found in rrLBCL tumors.

  Study EGAS50000001293

• RNA-Seq analysis of cocaine use disorder in Brodmann Area 9

  We aimed to identify cocaine use disorder associated changes in gene expression in the Brodmann Area 9 subregion of the human prefrontal cortex. RNA-sequencing was performed in N=13 individuals with and N=12 individuals without CUD. The individuals are originating from a cohort of N=42 individuals where DNA methylation (DNAm) levels were previously analyzed using the EPIC array.

  Study EGAS50000000150

• Somatic_mutation_in_skin_epidermis__SMS_

  We aim to assess the range and depth of mutations in genes linked with cancer in skin epidermis surrounding lesions which are undergoing surgical removal. Patient history will be collected to provide a detailed outline of tumour type (including histology), skin type, and sunlight exposure. We will perform ultra-deep targeted sequencing using genes implicated in cancer to try and understand the background of mutations surrounding these lesions

  Study EGAS00001002165

• Exome sequencing of paired primary tumor and metastatic breast cancer

  Prognosis evaluation of advanced breast cancer and therapeutic strategy are mostly based on clinical features of advanced disease and molecular profiling of the primary tumor. Very few studies have evaluated the impact of a prospective documentation of metastatic subtyping. The genomic landscape of metastatic breast cancer has mostly been described in very advanced, pretreated disease, limiting its transferability to clinical use.

  Study EGAS00001004578

• B Cell Receptor Study From Metastatic Breast Cancer Tumour Samples

  B and T cells are key components of the adaptive immune system and play an important role in anti-cancer immunity. In this study, we performed an integrative analysis of the B cell and T cell repertoires across 27 metastatic breast tumours obtained from 8 donors with therapy-resistant lethal metastatic breast cancer at the time of a warm autopsy.

  Study EGAS00001006976

• Extensive patient-to-patient single nuclei transcriptome heterogeneity in pheochromocytomas and paragangliomas

  Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors of varied genetic makeup, associated with high cardiovascular morbidity and a variable risk of malignancy. We focused on PCPG tumors with germline SDHB and RET mutations, representing distinct prognostic groups with worse or better prognoses, respectively. We applied single-nuclei RNA sequencing (snRNA-seq) on tissue samples from 11 patients.

  Study EGAS00001006230

• Full blood mRNA sequencing of myotonic dystrophy type 1 patients after cognitive behavioural therapy

  Myotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Here, we performed mRNA sequencing of full blood for 27 patients of the OPTIMISTIC cohort before and after the CBT intervention. We identified 608 genes for which their expression was significantly associated with the disease causing CTG-repeat expansion, as well as with 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes significantly associated with both returned to more normal levels in patients who benefited most from CBT. This trend was consistent with the difference observed between DM1 patients and controls in an earlier study of blood mRNA expression levels, singling these genes out as candidate biomarkers for therapy response. Together these results highlight the ability to find disease relevant information in full blood of DM1 patients and open new avenues to monitor therapy effects.

  Study EGAS00001005830

• NOTCH1 orchestrates metabolic reprogramming to drive proliferation in chronic lymphocytic leukemia

  In Chronic lymphocytic leukemia (CLL), NOTCH1 mutations occur in ~10% of cases and are often associated with unmutated IGHV genes, defining a subgroup requiring earlier treatment. Using an engineered CLL cell line, we demonstrated that NOTCH1-mutated cells exhibit increased glucose uptake, oxidative metabolism, and proliferation, driven by enhanced mitochondrial mass and TFAM upregulation. Metabolic assays and stable isotope tracing revealed a greater dependency on glutamine and anabolic pathways in NOTCH1-mutated cells, promoting growth. These findings were validated in a cohort of NOTCH1-mutated patients, highlighting a molecular circuit linking BCR, NOTCH1, and mitochondrial metabolism. This study suggests that metabolic vulnerabilities in NOTCH1-mutated CLL could inform precision medicine strategies.

  Study EGAS50000000981

• Non-ADT METs ICGC Prostate UK

  To characterize the subclonal genomic architecture of non-androgen-deprived metastatic prostate cancer, we performed whole-genome sequencing (WGS) of pelvic lymph node metastases and matching noncancerous blood from 10 patients to an average sequencing depth of 55x. The patients are part of PELICAN (Project to ELIminate Lethal Cancer) study led by G. Steven Bova at Johns Hopkins University (USA) and Tampere University (Finland). As of September 2020, study using these data is: Wedge et al, Nature Genetics 2018 (PMID: 29662167)

  Dataset EGAD00001002002

• Molecular characterization of Barrett’s esophagus at single cell resolution

  Backgrounds & Aims: Patient with Barrett’s esophagus (BE) have an increased risk to develop esophageal adenocarcinoma and are under periodical endoscopic surveillance for malignant transformation. Pathologists distinguish between different BE stages to identify high-risk patients, but this process remains difficult as stage-specific markers are still missing. We established BE organoid cultures, applied single cell sequencing approaches to identify differences in gene expression and genomic alterations, and validated candidate genes for their predictive value on histological sections. Methods: We collected 43 epithelial biopsies from 21 patients, established organoids for the clonal expansion of matching healthy and diseased tissue from two patients to identify genomic alterations by whole genome sequencing (WGS). We performed single cell DNA-sequencing (scDNAseq) to analyse DNA alterations within biopsies from 8 patients and single cell RNA-sequencing (scRNAseq) to identify gene expression differences between BE stages from 19 patients. Candidate marker genes were then validated by RNA in situ hybridization experiments on histological resection specimen. Results: Most BE biopsies were chromosomal stable (CS) and their single base substitution (SBS) signatures were indistinguishable from the healthy control tissues. Dysplastic BE cells contained areas of chromosomal instabilities (CIN), which differed by the presence of the SBS17 signatures from biopsy-matching CS cells or patient-matching healthy control cells. Such CIN areas affected efficient clustering of the scRNAseq data. We identified two sets of marker genes (SLC5A5, PSCA, LIPF and ANPEP, CEACAM6, REG4), which distinguish columnar BE epithelium from non-dysplastic/dysplastic stages. CLDN2 allowed the distinction between dysplastic and more advanced stages as its expression level increased and spread in dysplastic BE glands. Conclusions: Molecular characterization of BE samples identified a correlation between the presence of CIN and COSMIC signature 17, and we report seven marker genes that help in distinguishing different BE stages.

  Study EGAS00001005221

• PAX5 biallelic genomic alterations define a novel subgroup of B cell precursor acute lymphoblastic leukemia

  Chromosomal rearrangements and specific aneuploidy patterns are initiating events and define subgroups in B cell precursor acute lymphoblastic leukemia (BCP-ALL). Here we analyzed 250 BCP-ALL cases and identified a novel subgroup (‘PAX5-plus’, n=19) by distinct DNA methylation and gene expression profiles. All patients in this subgroup harbored mutations in the B-lineage transcription factor PAX5, with p.P80R as hotspot. Mutations either affected two independent codons, consistent with compound heterozygosity, or suffered LOH predominantly through chromosome 9p aberrations. These biallelic events resulted in disruption of PAX5 transcriptional programs regulating B cell differentiation and tumor suppressor functions. Homozygous CDKN2A/B deletions and RAS activating hotspot mutations were highly enriched as cooperating events in the genomic profile of PAX5-plus ALL. Together this defined a specific pattern of triple alterations, exclusive to the novel subgroup. PAX5-plus ALL was observed in pediatric and adult patients. Although restricted by the limited sample size, a tendency for more favorable clinical outcome was observed with 10 of 12 adult PAX5-plus patients achieving long-term survival. PAX5-plus represents the first BCP-ALL subgroup defined by sequence alterations in contrast to gross chromosomal events and exemplifies how deregulated differentiation (PAX5), impaired cell cycle control (CDKN2A/B) together with sustained proliferative signaling (RAS) cooperatively drives leukemogenesis.

  Study EGAS00001003209

• M116 scRNA-seq

  scRNA-seq was performed using Chromium Next GEM Single Cell 3’ Kit v3.1 (10X Genomics) according to the manufacturer’s instructions. Briefly, M116's PBMCs were thawed and quantified in order to calculate the number of cells to be loaded. Then, barcoded Single Cell 3ʹ Gel Beads, a master mix containing PBMCs, and Partitioning Oil were combined onto the Chromium Next GEM Chip G to generate Gel Beads-In-Emulsion (GEMs), where polyadenylated mRNAs were reverse transcribed. This way, all generated cDNAs from the same cell shared a common 10X Barcode. Following the reverse transcription, GEMs were broken and cDNAs were amplified and cleaned up with SPRIselect beads (Beckman Coulter®). Next, a portion of these cDNAs were enzymatically fragmented and subjected to adaptor ligation before using them as a PCR template for the incorporation of i5/i7 indexes. Finally, libraries were purified with SPRIselect beads, quantified and quality checked by using the 2200 TapeStation (Agilent®), and subjected to paired-end 150-bp sequencing (Novaseq systems, Illumina®) following standard practices at external facilities (Novogene®). Files types included in this dataset are raw Fastq files.

  Dataset EGAD50000001289

• RNA seq on 19 samples of Radiation-Induced Meningiomas

  Purpose: Majority of pediatric cancers require the irradiation of the central nervous system (CNS), and as more patients survive into adulthood from improved oncological therapy the sequelae of brain radiation are increasing in prevalence. Radiation-induced meningiomas (RIMs), one such secondary effect, demonstrate a clinically more aggressive behaviour than sporadic meningiomas (SMs). We aimed to describe the genomic mutational landscape of RIMs.Methods: We analyzed a principal cohort of 18 RIMs, with 31 RIMs overall, from patients who received childhood radiation therapy and 30 SMs, as a comparator population. We performed a multiplatform integrative genomic analysis; including methylation, whole exome and RNA sequencing. Results: RIMs exhibited a five-fold increase in copy number alterations, commonly the loss of chromosome 1p (17/18 RIMs) and 22q (17/18 RIMs), which was significantly more than observed in sporadic meningiomas. Furthermore, RNA sequencing data revealed an NF2 gene fusion event in 35.3% of RIMs. In all 6 cases, there was a complete NF2 exon spliced into a complete exon of a reciprocal gene, suggesting that the breakpoints of genomic rearrangement are intronic. All tumours with the NF2 fusion also possessed monosomy of chromosome 22q, rendering the cells with homozygous disruption of NF2. Clinically, RIMs with the NF2 fusion exhibited ill-defined borders and a tendency to develop in anatomic frontal location. Also, targeted sequencing panel confirmed that RIMs had fewer nonsynonymous NF2 mutations (6.5% vs. 30% in SM) and absence of mutations in TRAF7, SMO, KLF4, PIK3CA and AKT1, genes traditionally involved in SMs.Conclusion: Our study demonstrates that RIMs have distinct genomic drivers of oncogenesis as compared to SMs, specifically NF2 inactivation through fusion event. Radiation therapy possibly triggers genomic structural rearrangements through error-prone repair of double-stranded DNA breaks.

  Study EGAS00001002318