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• WGS data subfolder HFF7VCCXY from multifocal ileal NETs study

  This dataset includes linked-read whole-genome sequencing data (subfolder HFF7VCCXY) for multifocal ileal tumor samples from one patient. Samples were sequenced using the 10x Genomics linked-read whole-genome sequencing (WGS) approach.

  Dataset EGAD00001007075

• Sequencing data for oesophageal and related samples - OACs 496 release (WGS)

  Data from 496 OCCAMS (Oesophageal Cancer Clinical And Molecular Stratification) cases. WGS BAM files 496x oesophageal adenocarcinoma samples 496x normal samples

  Dataset EGAD00001007785

• Prevalence of transthyretin amyloidosis in patients with heart failure and no left ventricular hypertrophy

  The study prospectively enrolled patients admitted for HF with LV ejection fraction (LVEF) ≥ 50% and LV wall thickness <12 mm. TTR cardiac amyloidosis was diagnosed according to accepted criteria, which include positive cardiac 99-Tc-DPD scintigraphy in the absence of monoclonal protein expansion in blood. In a cohort of patients with HFpEF without LVH, the prevalence of TTR cardiac amyloidosis was 5%. Transthyretin gene sequencing was performed in positive patients.

  Dataset EGAD00001007787

• CPC-GENE primary prostate benign and tumour tissue Hi-C sequencing reads

  This dataset contains the raw sequencing data, in FASTQ format, for Hi-C assays from 17 primary prostate tissue samples. The sequencing data is paired-end, 150 bp sequencing data from an Illumina NovaSeq 6000 machine, and contains 5 benign tissue samples and 12 primary tumour samples from the Canadian Prostate Cancer Genome Network (CPC-GENE) project. Tumour samples have IDs starting with the "CPCG" prefix, and benign tissue samples have IDs starting with the "BP" suffix.

  Dataset EGAD00001008024

• Single cell study of infant leukemias

  We have performed single cell RNA-sequencing for infant and childhood B-cell acute lymphoblastic leukemias as well as infant acute myeloid leukemias at diagnosis. The sequencing was performed with 10X Chromium single cell 3’ and 5’ chemistry.

  Dataset EGAD00001007854

• Sequencing data for oesophageal and related samples - Ng, Contino et al (WGS)

  Data supporting "Interplay of processes shapes structural variations undergoing selection in oesophageal adenocarcinoma" Ng, Contino et al. WGS (BAM files) 383 oesophageal adenocarcinoma samples 383 normal samples

  Dataset EGAD00001007808

• Sequencing data for oesophageal and related samples - Katz-Summercorn, Jammula et al (WGS)

  Data supporting: “Multi-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals structural variation and retrotransposon activity occur early in cancer evolution.” Katz-Summercorn, Jammula et al. WGS (BAM files)

  Dataset EGAD00001006349

• mRNA-Seq on single human MII oocytes collected from gonadotropin stimulated women

  This dataset contains 11 paired-end FASTQ sequences from mRNA-Seq on single human M-II stage oocytes that were collected from gonadotropin stimulated women undergoing fertility treatments. M-II stage oocytes were collected and flash frozen prior to lysis followed by RNA extraction, full length cDNA preparation and amplification using the Ultra-low-input SMART-Seq2 v4 kit from Takara Clonetech. Further, these cDNA were used to prepare libraries for sequencing according the Nextera XT DNA library preparation kit from Illumina.

  Dataset EGAD00001006863

• Detection of Gene Fusions using Targeted Next-Generation Sequencing

  Five commercially available parallel sequencing assays were evaluated for their ability to detect gene fusions in eight cell lines and 18 FFPE tissue samples carrying a variety of known gene fusions. Four RNA-based assays and one DNA-based assay were compared; two were hybrid capture-based, TruSight Tumor 170 Assay (Illumina) and SureSelect XT HS Custom Panel (Agilent), and three were amplicon-based, Archer FusionPlex Lung Panel (ArcherDX), QIAseq RNAscan Custom Panel (Qiagen) and Oncomine Focus Assay (Thermo Fisher Scientific).

  Dataset EGAD00001006913

• Sequencing data for oesophageal and related samples - Scott et al (WGS, RNA)

  Data supporting: "Evidence that polyploidy in esophageal adenocarcinoma originates from mitotic slippage caused by defective chromosome attachments" Scott et al. WGS and RNAseq sequencing data Organoid, tumour and normal samples BAM files

  Dataset EGAD00001006738

• FASTQ files

  Raw FASTQ files obtained from in situ Hi-C of 16 normal B cells (3 naive B cells, 3 germinal center B cells, 3 plasma cells, and 3 memory B cells, together with a merge file for each subpopulation), 7 chronic lymphocytic leukemias (2 unmutated IGHV and 5 mutated IGHV), and 5 mantle cell lymphomas (2 conventional and 3 leukemic non-nodal).

  Dataset EGAD00001006485

• Resequencing (MIPS) of candidate genes for Keratoconus (2020)

  The dataset consists of the BAM-files of 745 patients and 810 controls (retained after quality control) of a set of 34 candidate genes obtained after targeted enrichment via Molecular Inversion Probes (MIPS) technology. The sequencing was performed on the NextSeq 500 (Illumina, CA, USA) using custom sequencing and index primers in three 2 x 76 bp, dual indexed runs using a 150 cycles High-Output Illumina kit (Illumina, CA, USA). Alignment of the fastq reads to the human genome was performed using BWA (v0.7.4).

  Dataset EGAD00001006825

• Detection of ctDNA in Plasma of Patients with Clinically Localised Prostate Cancer is Associated with Rapid Disease Progression

  Whole genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 hours and 6 weeks) surgery. Tagged-amplicon deep sequencing (TAm-Seq) across the TP53 gene in ctDNA in a cohort of 189 individuals.

  Dataset EGAD00001006369

• WGS data subfolder HF3NYCCXY from multifocal ileal NETs study

  This dataset includes linked-read whole-genome sequencing data (subfolder HF3NYCCXY) for multifocal ileal tumor samples from one patient. Samples were sequenced using the 10x Genomics linked-read whole-genome sequencing (WGS) approach.

  Dataset EGAD00001008494

• WGS data subfolder HFFWLCCXY from multifocal ileal NETs study

  This dataset includes linked-read whole-genome sequencing data (subfolder HFFWLCCXY) for multifocal ileal tumor samples from one patient. Samples were sequenced using the 10x Genomics linked-read whole-genome sequencing (WGS) approach.

  Dataset EGAD00001008495

• CCTG IND.231 WGS DNA Sequencing Data

  41 WGS DNA sequences from: Phase I trial of CX-5461, a first-in-class G-quadruplex stabilizer in patients with advanced solid tumors enriched for DNA-repair deficiencies (CCTG IND.231)

  Dataset EGAD00001008756

• H3Africa Consortium WGS VCF

  Joint called VCF for whole genome sequence data from 410 samples described in the paper: PMID:33116287. It includes 314 high coverage (average 30X) samples sequenced on the Illumina X-Ten, also available as individual datasets under the H3Africa Chip study (EGAS00001002976) and 112 medium coverage (average 10X) samples from the TrypanGen study (EGAS00001002602) sequenced on Illumina HiSeq 2500. Supplementary table 3 of the paper describes the geographic breakdown of the samples. 16 samples from the Southern African Human Genome project have been removed from this VCF.

  Dataset EGAD00001008577

• Dataset for synovial_sarcoma-RNA

  Rare cancer sequencing data of 23 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008844

• Anthropological dataset 1 for The admixture histories of Cabo Verde

  Datasets used in the article "The genetic and linguistic admixture histories of the islands of Cabo Verde" by Laurent R et al. eLife 2023 (DOI: https://doi.org/10.7554/eLife.79827 - URL: https://elifesciences.org/articles/79827) File name "eGAdeposit_233CaboVerde_SampleInfo_FINAL_01062022.txt" Column 1 corresponds to individual alphanumeric codes as in the "eGAdeposit_233CaboVerde_GenotypeFile_FINAL_01062022.vcf" genotype file Column 2 corresponds to individual's biological sex as per genetic inference Column 3 corresponds to individual's self-reported age in years Column 4 corresponds to individual's self-reported cumulated number of years spent in academic or professional education

  Dataset EGAD00001008976

• Single cell RNA sequencing of bone marrow mononuclear cells from healthy donors and B-cell lymphoma patients following CD19 CAR T-cell therapy

  Bone marrow aspirates were obtained from patients with relapsed/refractory large B cell lymphoma (rrLBCL), mononuclear cells isolated by ficoll density-gradient centrifugation, and loaded onto a 10X Chromium for single cell RNA-sequencing using 5’ chemistry without prior cryopreservation. Healthy donor bone marrow mononuclear cells were obtained from healthy allogeneic stem cell transplant donors and analyzed following viable cryopreservation.

  Dataset EGAD00001009774

• GELATO clinical trial RNA-Seq data (metastatic lesions)

  RNA-Seq data of 46 matched lobular breast cancer metastatic samples obtained from 21 unique patients from GELATO clinical trial assayed at three timepoints: at baseline (directly after patient randomization), pre-atezolizumab (after induction treatment with carboplatin for two weeks) and on atezolizumab (after two cycles of atezolizumab combined with carboplatin). The included raw transcriptome sequencing data in fastq format was generated using Illumina NovaSeq 6000 from fresh frozen material.

  Dataset EGAD00001009834

• Human CCO+ liver mtDNA sequencing

  BAM files containing paired-end mtDNA sequencing data from morphologically normal human liver. CCO-proficient hepatocytes acquired from human livers in which clonal CCO-deficient hepatocyte patches had been previously identified. Individual BAM files are named according to their patch, line and sample location, where PT denotes tissue near to the portal triad (PT), central hepatic vein (CV) and midway between these two structures (Mid). "Stroma" control samples were used for identifying germ-line variants. Sequenced on NextSeq 500 platform.

  Dataset EGAD00001010016

• Whole Exome and RNA-Sequencing of Germline, Small Bowel Carcinoid Primary Tumor, and Liver Metastasis Trios

  This dataset includes trios of germline/constitutional, primary tumor (small bowel carcinoid), and metastatic tumor (liver) trios for 5 patients (i.e. 15 samples total). Constitutional, primary tumor, and metastatic tumor samples all underwent whole exome sequencing (WES or WXS). Primary and metastatic tumor samples underwent RNA sequencing (RNA-seq).

  Dataset EGAD00001010036

• Organoid Derivation Project: TGS (2023-06-22)

  Sequencing of tissue samples and their derived organoids from oesophageal, pancreatic and colorectal cancer patients. . This dataset contains all the data available for this study on 2023-06-22.

  Dataset EGAD00001011089

• Organoid Derivation Pilot: RNAseq (2023-06-22)

  Sequencing of tissue samples and their derived organoids from oesophageal, pancreatic and colorectal cancer patients. . This dataset contains all the data available for this study on 2023-06-22.

  Dataset EGAD00001011091

• Organoid Derivation Project - GRCh38 - TGS (2023-06-22)

  Sequencing of tissue samples and their derived organoids from oesophageal, pancreatic and colorectal cancer patients. . This dataset contains all the data available for this study on 2023-06-22.

  Dataset EGAD00001011094

• limbal stem cells from Aniridia patients

  Limbal stem cells obtained during penetrating keratoplasty from aniridia patients with congenital aniridia (Lagali Stage 4), limbal tissue was digested in collagenase A solution (4 mg/ml) in keratinocyte serum-free medium (KSFM) (Thermo Fisher Scientific; Waltham, MA) for 20 h at 37 °C. Cell suspensions were filtered through a use of Flowmi® micro strainer (SP Bel-Art; Wayne, NJ). LSC clusters were dissociated with trypsin-EDTA (0.05%) solution and cultivated in KSFM. Medium was refreshed every other day. Subconfluent (80–90%) limbal epithelial cells were harvested at passage 2

  Dataset EGAD00001011124

• HiChIP bulk

  This dataset gather HiChIP data for H3K27ac mar in MM.1S cell line in control and Dex condition, both in two biological replicates

  Dataset EGAD00001011138

• Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma - RNA-Seq

  This study aims to investigate the dysregulation of RNA translation and identify functional non-canonical open reading frames (ORFs) as potential targets for medulloblastoma treatment. The study involves ribosome profiling and RNAseq of medulloblastoma tissues and cell lines to observe the translation of non-canonical ORFs. Multiple CRISPR-Cas9 screens will be used to identify functional non-canonical ORFs implicated in medulloblastoma cell survival.

  Dataset EGAD00001011192

• Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma - Ribo-Seq

  This study aims to investigate the dysregulation of RNA translation and identify functional non-canonical open reading frames (ORFs) as potential targets for medulloblastoma treatment. The study involves ribosome profiling and RNAseq of medulloblastoma tissues and cell lines to observe the translation of non-canonical ORFs. Multiple CRISPR-Cas9 screens will be used to identify functional non-canonical ORFs implicated in medulloblastoma cell survival.

  Dataset EGAD00001011193

• ATAC-Seq/Hi-C/4C-Seq dataset for Malignant rhabdoid study

  Study describing the dynamics of chromatin organization within malignant rhabdoid tumors. This study describes how this chromatin organization changes upon SMARCB1 rescue within patient-derived organoid models from malignant rhabdoid tumors. Identification of a novel super-enhancer of MYC and identification of patient-specific enhancer utilization to activate MYC expression in these tumors.

  Dataset EGAD00001011820

• V(D)J and 5' Gene Expression data of bone marrow cells from patients with aplastic anemia

  Viably frozen blood MNCs from 9 cGVHD patients were sorted with BD Influx Cell sorter, to enrich for CD45+ cells. Gene and V(D)J transcript profiles were studied with 10x Genomics Chromium Single Cell Immune Profiling platform. The Chromium Single Cell 5’RNAseq run and library preparation were done using the Chromium Next GEM Single Cell Immune Profiling version 1.1 chemistry. The raw data was processed using Cell Ranger v3.1 pipelines.

  Dataset EGAD00001012117

• Comprehensive Deep Sequencing Atlas in HCC tumors

  The atlas aims to unravel the intricate genetic landscape of HCC, providing a detailed characterization of genomic alterations, transcriptomic profiles, and key mutations associated with liver tumors. The integration of WGS, RNAseq, and WES data offers a holistic perspective, facilitating a deeper understanding of the molecular mechanisms driving HCC pathogenesis. The resulting atlas serves as a valuable resource for researchers, clinicians, and the broader scientific community, contributing to advancements in HCC diagnostics, prognostics, and therapeutic interventions.

  Dataset EGAD00001015343

• ICU transcriptomics: Assessing the role of the host immune response in patients with ventilator-associated pneumonia

  This is a study of 100 patients with the aim to provide transcriptomic sequencing data analysis of cells isolated from bronchioalveolar lavage and blood samples from critically ill patients with pneumonia on an intensive care unit in order to investigate the host contribution to disease. 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 EGAD00001015407

• Whole-genome sequencing of rhabdomyosarcoma tumouroids (2025-09-30)

  This study investigates high-risk rhabdomyosarcoma (RMS) using multiple single-cell and spatial genomic technologies. We generated and analysed single-cell and single-nucleus RNA-sequencing, chromatin accessibility, and spatial transcriptomics data from primary tumours and validation samples. These datasets characterise cellular diversity within rhabdomyosarcoma and identify cell states associated with aggressive disease. The data support research into tumour biology, risk stratification, and therapeutic target discovery. This repository houses the whole-genome sequencing of RMS tumoroids data. . This dataset contains all the data available for this study on 2025-09-30.

  Dataset EGAD00001015707

• Single-cell RNA-sequencing of rhabdomyosarcoma tumouroids (2025-09-30)

  This study investigates high-risk rhabdomyosarcoma (RMS) using multiple single-cell and spatial genomic technologies. We generated and analysed single-cell and single-nucleus RNA-sequencing, chromatin accessibility, and spatial transcriptomics data from primary tumours and validation samples. These datasets characterise cellular diversity within rhabdomyosarcoma and identify cell states associated with aggressive disease. The data support research into tumour biology, risk stratification, and therapeutic target discovery. This repository houses the single-cell RNA sequencing of RMS tumouroids data. . This dataset contains all the data available for this study on 2025-09-30.

  Dataset EGAD00001015708

• Whole Genome-sequencing of rhabdomyosarcoma tumour tissue (2025-09-30)

  This study investigates high-risk rhabdomyosarcoma (RMS) using multiple single-cell and spatial genomic technologies. We generated and analysed single-cell and single-nucleus RNA-sequencing, chromatin accessibility, and spatial transcriptomics data from primary tumours and validation samples. These datasets characterise cellular diversity within rhabdomyosarcoma and identify cell states associated with aggressive disease. The data support research into tumour biology, risk stratification, and therapeutic target discovery. This repository houses the whole-genome sequencing of RMS tumours data. . This dataset contains all the data available for this study on 2025-09-30.

  Dataset EGAD00001015709

• Bulk RNA-sequencing of rhabdomyosarcoma tumour tissue (2025-09-30)

  This study investigates high-risk rhabdomyosarcoma (RMS) using multiple single-cell and spatial genomic technologies. We generated and analysed single-cell and single-nucleus RNA-sequencing, chromatin accessibility, and spatial transcriptomics data from primary tumours and validation samples. These datasets characterise cellular diversity within rhabdomyosarcoma and identify cell states associated with aggressive disease. The data support research into tumour biology, risk stratification, and therapeutic target discovery. This repository houses the bulk RNA sequencing of RMS tumours data. . This dataset contains all the data available for this study on 2025-09-30.

  Dataset EGAD00001015714

• Whole Genome-sequencing of rhabdomyosarcoma tumour tissue (2025-09-30)

  This study investigates high-risk rhabdomyosarcoma (RMS) using multiple single-cell and spatial genomic technologies. We generated and analysed single-cell and single-nucleus RNA-sequencing, chromatin accessibility, and spatial transcriptomics data from primary tumours and validation samples. These datasets characterise cellular diversity within rhabdomyosarcoma and identify cell states associated with aggressive disease. The data support research into tumour biology, risk stratification, and therapeutic target discovery. This repository houses the whole-genome sequencing of RMS tumours data. . This dataset contains all the data available for this study on 2025-09-30.

  Dataset EGAD00001015716

• Bulk RNA-sequencing of rhabdomyosarcoma tumour tissue (2025-09-30)

  This study investigates high-risk rhabdomyosarcoma (RMS) using multiple single-cell and spatial genomic technologies. We generated and analysed single-cell and single-nucleus RNA-sequencing, chromatin accessibility, and spatial transcriptomics data from primary tumours and validation samples. These datasets characterise cellular diversity within rhabdomyosarcoma and identify cell states associated with aggressive disease. The data support research into tumour biology, risk stratification, and therapeutic target discovery. This repository houses the bulk RNA sequencing of RMS tumours data. . This dataset contains all the data available for this study on 2025-09-30.

  Dataset EGAD00001015718

• deCODE Genetics study on genes contributing to nicotine dependence in humans

  A genome-wide association study on smoking behavior and nicotine dependence in Icelandic smokers, assessed by the number of cigarettes smoked per day, smoking initiation and degree of dependence on nicotine. The number of cigarettes smoked per day was ascertained through questionnaires given to individuals participating in multiple disease projects at deCODE Genetics (n=16,483). Smoking initiation was analyzed by comparing those that have ever smoked (n=16,483) versus those that have never smoked (n=21,667). The nicotine dependence analysis included 3,435 nicotine dependent cases (score 4 or higher on Fagerstrom Test for Nicotine Dependence (FTND) or endorsement of at least three of the seven Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria) and 3,344 low-quantity smokers as controls.

  Study phs000393

• PD-1 Instructs a Tumor Suppressive Metabolic Program to Restrain AP-1 Activity in T Cell Lymphoma

  T cell non-Hodgkin lymphomas (T-NHLs) represent a heterogeneous group of aggressive cancers of mature CD4+ T cells, for which therapeutic options are limited. Recent work uncovered that the PDCD1 encoded immune checkpoint receptor PD-1 is a key tumor suppressor in T cells. PD-1 is recurrently inactivated in T-NHL and the highest frequencies of PDCD1 deletions are detected in advanced disease, predicting worse prognosis. The tumor-suppressive mechanisms of PD-1 signaling remain unknown. In the present study, we identify transcriptional and epigenetic mechanisms underlying PD-1 tumor suppression in T-NHL.Some subjects included in this study overlap with the subjects from phs002456. To establish the link between the overlapping subjects, the Subject Consent datasets will be utilized.

  Study phs003312

• Genome Sequencing of Hepatocellular Carcinoma at The Human Genome Sequencing Center of Baylor College of Medicine (HGSC-BCM)

  Hepatocellular carcinoma (HCC) accounts for 85-90% of primary liver cancers. We have focused on three major HCC etiologies:hepatitis C virus (HCV), hepatitis B virus (HBV), and nonviral causes. The onset and progression of cancer is driven by extensive rearrangement and mutation of the genome. We combined our capability to capture and enrich exome DNA with the next generation sequencing capacity to allow us to detect and characterize the somatic mutation profile of patients with HCC. Patient samples were collected by the Liver Center, Division of Abdominal Transplantation in the Baylor College of Medicine Department of Surgery. Sequencing of HCC is one of the NHGRI Center Initiated Projects in progress in the Human Genome Sequencing Center at Baylor College of Medicine.

  Study phs000509

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): Large Scale Flu Surveillance Study (LSFS)

  The purpose of this study was to better understand behavioral and physiological functioning in relation to recent self-reported influenza and influenza-like-illness (ILI), including coronavirus disease (COVID-19). Over 65,000 Achievement members responded to a weekly one-click survey asking if they had experienced ILI within the previous 7-day period. If they responded no, they were given the option to complete a survey about their risk factors and behavior. If they responded yes, they were given the option to complete a survey asking about the specifics of the incident. Participants were also asked to sync their wearable activity trackers and health apps in order for researchers to better understand changes in behavioral and physiological outcomes related to self-reported ILI experiences.DOI: https://rapids.ll.mit.edu/10.57895/fkth-d352

  Study phs002539

• NHLBI TOPMed: Australian Familial Atrial Fibrillation Study

  In the Australian Familial AF Study, a cohort of probands with familial AF was recruited for genetics studies at the Victor Chang Cardiac Research Institute. Familial AF cases were identified from in-patient and out-patient populations at St. Vincent's Hospital and by referral from collaborating physicians throughout Australia. Study subjects underwent clinical evaluation with history, ECG and echocardiogram, and informed consent was obtained from all participants. 151 probands aged <66 years at the time of diagnosis were included in this analysis. The control cohort was comprised of age- and sex-matched individuals (n=151) who had no history of cardiovascular disease. In the current TOPMed study, we have performed whole genome sequencing in European Ancestry cases with early-onset atrial fibrillation (defined as atrial fibrillation onset prior to 61 years).

  Study phs001435

• The Longevity Genes Project

  Aging is a complex, universal condition leading to the functional decline of all cells and organisms, and to major national and global public health problems. Although aging is the major risk factor for developing most adult-onset diseases, systematic investigations into the fundamental physiology, biology and genetics of aging are only just beginning. In the Longevity Genes Project at Albert Einstein College of Medicine, Dr. Nir Barzilai and his team conducted genetic research on more than 500 healthy elderly people between the ages of 95 and 112, and on their children. The identification of longevity genes by Einstein researchers could lead to new drug therapies that might help people live longer, healthier lives and avoid or significantly delay age-related diseases such as Alzheimer's disease, type 2 diabetes and cardiovascular disease.

  Study phs000584

• The Mood and Methylation Study (MMS)

  The Mood Methylation Study (MMS) is an observational study designed to understand epigenetic mechanisms underlying major depression symptoms (MDD) using a co-twin control design. Twins enrolled in the MMS were monozygotic (MZ) twin pairs discordant on lifetime history of MDD. All twins were members of the Washington State Twin Registry (WSTR), a community-based twin registry consisting of over 10,000 twin pairs. Lifetime and current MDD diagnoses were determined using the Structured Clinical Interview for DSM-IV Research Version (SCID-4-RV). DNA methylation in blood monocytes was measured using the Infinium HumanMethylationEPIC BeadChip. Monocyte gene expression was quantified by paired end RNA-seq (50 PE). Zygosity of the twin pairs included in the MMS was self-reported and confirmed using the polymorphic SNPs included in the DNA methylation array.

  Study phs002858

• NIDDK⁄CIDR Inflammatory Bowel Disease Genetics Consortium (IBDGC) Genome Wide Association Study in Familial Crohn's Disease

  The National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium (NIDDK - IBDGC) conducted a genome wide association study (GWAS) using the Human Omni2.5-Quad beadchip from Illumina to identify disease variants associated with familial Crohn's disease. This study includes a subset of individuals from an original cohort of affected subjects and affected/unaffected relatives from a previous linkage scan which showed increased linkage evidence at three novel risk loci. A total of 708 samples were selected based on various criteria for inclusion from the 6 Genetic Research Centers (GRC) in North America that participate in the IBDGC. This project was supported by an ancillary R01 grant from the NIDDK with resources made available through the IBDGC.

  Study phs000367

• The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

  This study was the first-known large-scale effort to uncover the mutational spectrum of head and neck cancers. We analyzed whole-exome sequence from 92 tumor-normal pairs and retained 74 of them for significance analysis. The majority exhibited a mutational profile consistent with tobacco exposure; human papilloma virus sequence was detectable in 15% of cases. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), the analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbor mutations in genes (such as NOTCH1, IRF6, TP63) that regulate squamous differentiation, implicating alterations in this process as a major driver of HNSCC carcinogenesis. Altogether, the results suggest that large-scale exome sequencing may illuminate fundamental tumorigenic mechanisms with important therapeutic implications.

  Study phs000370

• HuBMAP: Single-Cell Data from Human Tissues

  The small bowel and colon are organs critical for maintaining homeostasis of the human body by mediating nutritional absorption upon the ingestion of food. Though both organs are extensive in length, there are known differences in function and cellular heterogeneity within different portions of each. Also, a cross section anywhere in the bowel reveals a complex layering of components involved in absorption and secretion, motility of gut contents, circulation, and immunity. We are mapping the complexity of the the small bowel and colon with cell-to-cell resolution in histologic sections, both along their lengths and across multiple individuals. Our molecular data consist of single cell ATAC-seq and RNA-seq. These profiles are spatially mapped to histologic sections using CO-Detection by indEXing (CODEX), a highly multiplexed system of antibody-tagged target epitopes.

  Study phs002272

• Time Lapse to Cancer-Defining the Transition from Polyp to Cancer

  In the US, CRC incidence has declined with uptake in colonoscopy for early detection and removal of polyps, the precursor lesion, can stop a cancer from developing but in spite of this, CRC remains the second leading cause of cancer death in the United States. One third of people who undergo screening colonoscopy will have adenomatous polyps, but less than 5% of the time are these polyps presumed to go on to develop into cancer. Why does one polyp develop into cancer while another one that looks very similar does not. In this proposal we will identify what molecular genetic changes in the genome, in the mRNA expression and genetic methylation patterns will distinguish a polyp that has already transformed into cancer from one that has not.

  Study phs001384

• Melanoma Brain Metastasis Single-Cell RNA Sequencing Atlas

  Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma, yet our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBM (scRNA-seq n=5; snRNA-seq n=17) and 10 extracranial melanoma metastases (ECM; all snRNA-seq), and matched spatial single-cell transcriptomics (n=16) and T cell receptor (TCR)-seq (n=5). Key observations were validated in matched bulk RNA- and ATAC-seq of isogenic MBM/ECM cell culture models (n=24; including triplicates (labeled as *-A, -B and -C) of 4 MBM- and 4 ECM-derived patient cell lines with 2 matched pairs). This work provides comprehensive insights into MBM biology and serves as a foundational resource for further discovery and therapeutic exploration.

  Study phs002944

• GWAS in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture

  The study comprises SLE patients recruited from specialist rheumatology clinics from the United States, Mexico, Argentina, Chile and Peru. Two strategies were used to enrich samples for Native American ancestry: a. previously genotyped Hispanic and Latin American and US Native American individuals were selected according to their ancestry based on 253 ancestry informative markers as part of the Lupus Large Association 2 Study. The approximate 35% of the samples were primarily of European and Native American admixture was selected; b. the recruitment of patients took place primarily in countries with little African admixture. All samples were genotyped on the HumanOmni1-Quad BeadChip using manifest H at the Oklahoma Medical Research Foundation. The Illumina clustering algorithm with GenomeStudio v2011.1 was used.

  Study phs001025

• Hereditary Cancer Predisposition Syndromes and Uveal Melanoma

  Uveal melanoma (UM) is a subtype of melanoma characterized by the strong contribution of genetic rather than environmental factors in the pathogenesis of the disease, making it an ideal model disease to study the genetic basis of cancer. The long-term goal of our laboratory is to determine the genes and mechanisms responsible for hereditary cancer predisposition associated with UM. BAP1 has been identified as a candidate gene with definitive association with predisposition to UM. However, pathogenic variants in BAP1 are detected in only a small subset of UM patients even those with strong personal and family history of cancer suggesting the existence of other candidate genes. The goal of this project is to identify novel candidate genes contributing to hereditary predisposition to UM in patients with no detectable germline pathogenic variant in BAP1.

  Study phs001943

• Targeted Genomic Sequencing in Large Human Genes to Detect Induced Structural Variants

  Partial inhibition of DNA replication leads to de novo copy number variant (CNV) formation throughout the genome, especially at common fragile sites (CFSs). We previously showed that these hotspots for genome instability reside in late-replicating domains associated with large, transcribed genes. In this study, we performed targeted, error-corrected genomic sequencing of multiple large genes in several human cell lines. The svCapture pipeline was used to call novel structural variant junctions in co-analyzed samples. Multiple samples were analyzed from cell populations under different replication stresses, with suppression of DNA repair pathways, and in different cell cycle stages, to determine the mechanisms underlying CNV formation at these loci. Data are provided as raw genome sequencing reads and processed multi-sample VCF files with sequenced junctions encoded as breakends.

  Study phs003121

• AACR Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE)

  AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) is an international pancancer registry of real-world data assembled through data sharing between 19 leading international cancer centers with the goal of improving clinical decision-making. The registry leverages ongoing clinical sequencing efforts (CLIA/ISO-certified) at participating cancer centers by pooling their data to create a novel, open-access registry to serve as an evidence base for the entire cancer community. Genomic and baseline clinical data from more than 70,000 tumors is accessible through the efforts of our strategic and technical partners, Sage Bionetworks and cBioPortal. The consortium and its activities are driven by openness, transparency, and inclusion to ensure that the project output remains accessible to the global cancer research community and ultimately benefits patients.

  Study phs001337

• Transcriptomics of Liver and PBMCs in Alcohol-Associated Liver Disease

  This study was designed to characterize the transcriptome of alcohol-associated hepatitis using RNA sequencing (RNA-seq) technology for both liver tissue biopsies and peripheral blood mononuclear cells (PBMCs) extracted from blood samples, in order to identify expressed genes that are markers of the disease. To distinguish genes that differentiate alcohol-associated hepatitis from other inflammatory liver diseases, we compared the RNA-seq data generated from participants with alcohol-associated hepatitis, alcohol-associated cirrhosis, chronic hepatitis C infection, non-alcohol-associated fatty liver disease, and healthy controls. We utilized computational approaches to demonstrate that gene expression data generated from either liver tissue or blood samples can be used to identify a small set of gene biomarkers to distinguish between these liver diseases. The raw RNA-seq data will be available through dbGaP.

  Study phs003112

• Somatic Mutations in Epilepsy: Whole Genome Sequence Analysis of Single Neurons

  Low-coverage whole-genome sequencing was performed on single-cells from resected brain tissues obtained from an individual with hemimegalencephaly (HMG) along with a somatic copy number variant (sCNV) of chromosome 1q in order to characterize the sCNV at the single cell level. Single neuronal nuclei and non-neuronal nuclei were isolated by fluorescence-activated cell sorting (FACS) using NeuN immunoreactivity to identify neurons. 46 neurons and 30 non-neuronal cells, as well as a batch of 10 and a batch of 100 cells from each group, were genome amplified using multiple displacement amplification (MDA) and sequenced on an Illumina HiSeq 2000 sequencer. Thirty-two samples were multiplexed into each HiSeq lane for single-end 50 bp runs, obtaining ~5 million pass-filter reads per sample.

  Study phs002615

• Tracking Therapy-Resistant Alterations in Childhood Acute Lymphoblastic Leukemia

  Relapse is currently the major cause of death in children with B-ALL. The goal of this study is to uncover the genetic underpinnings of relapsed B-ALL in the AALL1331 cohort (PMID: 33651090) via whole genome and transcriptome sequencing of matched diagnosis, relapse, and remission specimens. We aim to discover genetic alterations that drive treatment resistance in relapsed tumors. We also aim to investigate the feasibility of detecting residual tumors from remission samples with the ultimate goal to improve risk stratification using NGS-based minimal residual disease (MRD) detection. Here we only report data from patients in remission with the aim of determining MRD. We will submit corresponding data for the diagnosis and relapse components of our cohort in a future version of our study.

  Study phs003409

• Single-Cell Atlas of Human Liver and Blood Immune Cells Across Fatty Liver Disease Stages

  The goal of the study was to investigate immunological correlates of human fatty liver disease progression. We generated a single-cell RNA-seq (scRNA-seq) atlas of immune cells from liver fine needle aspirates (FNAs) and paired peripheral blood mononuclear cells (PBMCs) from a full-spectrum Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) human cohort, using the 3' 10X Genomics platform. Using computational analyses to assess changes in cellular frequencies and function, we found heightened immunoregulatory programs with profibrotic potential alongside a shift from antigen-specific to natural killer cytotoxic functions in the liver with MASH progression. Available data include raw single-cell transcriptomic data (FASTQ files) for each sample type (PBMC, FNA) per patient alongside clinical and histological measurements of fatty liver disease.

  Study phs004044

• Whole genome sequencing of human induced pluripotent stem cells derived from 5 type I cyctic biliary atresia patients

  We have successfully generated a panel of human induced pluripotent stem cells (hiPSCs) from five Japanese patients carrying type I cystic biliary atresia (BA). These hiPSC lines have exhibited characteristics of self-renewal and pluripotency. These cells held normal karyotypes mostly, but one of them carried hemizygous deletions, of which clinical significance is unknown yet. Whole genome sequence analysis indicated that some of the mutations or single nucleotide polymorphisms (SNPs) commonly found in these patients are related to hepatobiliary abnormality. Given the limited understanding of the molecular pathogenesis of cystic BA, attributed to unknown factors of genetic and environmental causes, these cellular resources will be instrumental in replicating disease phenotypes and in the advancement of novel therapies for this condition.

  Study JGAS000765

• exploration of biomarkers discriminating squamous cell carcinoma from other lung cancers

  Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed. To achieve this goal, we initially performed CAGE (Cap Analysis of Gene Expression) to quantify promoter activities on 97 frozen tissues from surgically resected lung cancers (22 SCC and 75 AD). We furhter expanded the transcriptome profiling to cover additional 48 malignant neoplasm of bronchus and lung, including mesothelioma and metastatic lung cancers derived from other tissues.

  Study JGAS000488

• High-coverage whole exome sequence in non-TRU-type lung adenocarcinomas

  In order to elucidate the key genetic events in non-TRU-type lung cancer, we selected 43 non-TRU-type lung adenocarcinomas and performed a whole exome sequence and RNA-seq analysis using a next-generation sequencer. The results of the analysis identified mutations in TP53, KRAS and NKX2-1 as the top three significantly mutated genes, while the EGFR mutation was rare in this cohort. Eight NKX2-1 mutations (5 frameshift, 2 nonsense, and one missense) were identified, with one case harboring two distinct NKX2-1 mutations (missense and frameshift). All NKX2-1 mutants were transcriptionally inactive in reporter assays. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2-1 mutations (5 cases), while 1 enteric and 1 acinar adenocarcinoma harbored the NKX2-1 mutation.

  Study JGAS000105

• Transcriptomic profiling of circulating regulatory T cells from follicular lymphoma patients before and after Lenalidomide treatment

  Lenalidomide has demonstrated a favorable efficacy profile in follicular lymphoma (FL) in combination with anti-CD20 antibodies. However, in vivo administration of Lenalidomide in FL patients triggers a proliferation of functional regulatory T cells (Tregs), and a high percentage of Tregs before and along the course of treatment with Lenalidomide/anti-CD20 combination is of poor prognosis. In this study, we evaluated the impact of Lenalidomide on circulating Treg in 3 FL patients using single cell RNA sequencing (scRNAseq). For this purpose, we took advantage of the GALEN clinical trial (NCT01582776), where Lenalidomide was initiated one week before starting the anti-CD20 antibody Obinutuzumab, allowing us to compare the transcriptomic profile of immune cells before (D0) and at day 7 (D7) of treatment by Lenalidomide alone.

  Study EGAS50000001048

• Longitudinal_Cambridge_Study_COVID19

  Investigating tissue immune responses to SARSCoV-2 in live and deceased donors This project is part of a longitudinal clinical study that will be run from Cambridge University Medical School (Joseph Cheriyen) studying covid-19 infected patients. The Clatworthy project would use single cell approaches to study severe fatal versus non-fatal in old and old versus young patients and will also provide some information on male versus female. This work will provide single cell resolution insights into immune response to the virus, providing vital information on the biology of covid-19 infection. 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/

  Study EGAS00001004488

• Phase Ib of olaparib and capivasertib

  Background: Combining poly(ADP-ribose) polymerase (PARP) with phosphatidylinositol-3-kinase (PI3K) pathway inhibitors is supported by strong preclinical rationale. We sought to assess safety and a recommended phase 2 dose (RP2D) for the PARPi olaparib combined with the AKT inhibitor, capivasertib, and evaluate molecular markers of response and resistance. Methods: As part of a larger phase 1b trial, we performed a safety lead in of olaparib and capivasertib followed by expansion (n=24) in endometrial, triple negative breast, ovarian, fallopian tube, or peritoneal cancer. Olaparib 300mg orally twice daily and capivasertib orally twice daily on a 4 day on/3 day off schedule were evaluated. Two dose levels (DL) were planned: capivasertib 400mg (DL1); capivasertib 320mg (DL-1). Patients underwent biopsies at baseline and after 28 days.

  Study EGAS00001004930

• Assessment of the Toll-like receptor 3 response in hepatocytes

  Toll like receptor 3 (TLR3) is an endosomal pattern recognition receptor (PRR), recognizing double stranded RNA (dsRNA) as a distinct Pathogen-associated molecular pattern (PAMP) for viral infections. We aim to understand the contribution of TLR3 to the dsRNA response in hepatocytes. The innate immune response of cells of hepatic origin (Huh7, Huh7.5, PH5CH and primary human hepatocytes (PHH)) was analyzed by transcriptome analysis (RNAseq) upon supernatant delivery or transfection of synthetic dsRNA (poly(I:C)). Expression of TLR3 and RIG-I was reconstituted by lentiviral transduction in Huh7 and Huh7.5 cells. Huh7 and Huh7.5 cells, devoid of functional TLR3 expression, did not respond to supernatant delivery of poly(I:C), in contrast to PH5CH and PHH, confirming a high selectivity of this method towards activating TLR3 in all hepatocyte models.

  Study EGAS00001005147

• Tumor-associated preferred end coordinates and somatic variants as signatures of circulating tumor DNA

  Cell-free DNA fragmentation is a nonrandom process. We showed that cell-free DNA fragments with ends at certain genomic coordinates had higher likelihoods of being derived from hepatocellular carcinoma. Other coordinates were associated with cell-free DNA molecules originating from the liver. Quantitative assessment of cell-free DNA molecules bearing these respective groups of end signatures correlated with the amounts of tumor-derived or liver-derived DNA in plasma. There were millions of tumor-associated plasma DNA end coordinates across the genome. Due to their high prevalence, they were more readily detectable than somatic mutations as a cancer signature in plasma. Hence, detection of tumor-associated plasma DNA ends may offer a cost-effective means of capturing evidence for the presence of cancer through liquid biopsy assessment.

  Study EGAS00001003160

• The KATHERINE study of adjuvant trastuzumab emtansine in HER2-positive breast cancer: analysis of patients with HER2-negative residual invasive disease on re-testing

  Following chemotherapy and human epidermal growth factor 2 (HER2)-targeted neoadjuvant therapy for HER2-positive early breast cancer, residual invasive breast cancer at surgery may be HER2-negative on retesting in some patients. We evaluated outcomes with T-DM1 and trastuzumab in patients randomized in the phase III KATHERINE trial based on HER2-positive central testing of the core biopsy with HER2-negative central testing on their corresponding surgical specimen. In the 70/845 (8.3%) patients with HER2-negative residual disease on retesting at surgery, there were 11 IDFS events in the 42 trastuzumab-treated patients (26.2%) and none in the 28 T-DM1-treated patients, suggesting that T-DM1 should not be withheld in this patient population.

  Study EGAS00001006037

• Genome-wide expression profiles to compare array-based, RNAseq and NanoString technologies in patients with resected pancreatic ductal carcinoma.

  Using formalin-fixed paraffin embedded (FFPE) tissues collected prospectively in patients with resected pancreatic ductal carcinoma (PDC) we generated genome-wide expression profiles to compare array-based, RNAseq and NanoString technologies. Samples included in the study were collected 17 patients. After careful selection by the pathologist of 17 malignant cells-enriched, 7 stroma-enriched, and 6 normal (normal pancreas in 4 cases and normal duodenum in 2 cases) regions, sections were macrodissected, and total RNA extracted. Two additional FFPE-frozen matched-paired PDAC from our local Biobank were included. Our study represents the most extensive work comparing three technologies to generate gene expression profiles from FFPE samples, and provides technical guidance for future biomarker studies in samples collected prospectively in the context of clinical trials.

  Study EGAS00001002501

• UAMS Smoldering Myeloma Timeline Cohort

  To better understand the pattern of genetic changes over time, we performed whole exome sequencing of sequential bone marrow samples from 9 patients taken overtime including some paired SMM/newly diagnosed MM/Relapse MM samples. Samples from 9 patients (9 controls and 53 tumors) underwent whole exome sequencing with an additional capture for the IGH, IHK, IGL, and MYC loci. DNA was obtained from either CD138+ cells from the bone marrow of smoldering myeloma patients through time (tumor) or from stem cell harvests or peripheral blood cells from the same patient (control). 100 ng of DNA was fragmented, end-repaired, and adapters ligated using NimbleGen's MedExome. After PCR amplification hybridized libraries underwent further amplification before being sequenced on a NextSeq500 (Illumina) using 75 bp paired end reads.

  Study EGAS00001003687

• Single_cell_HSC_colony_WGS_many_years_post_allogeneic_bone_marrow_transplant

  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.

  Study EGAS00001003744

• Non-Mendalian inheritance of extrachromosal DNA elements can drive disease evolution in glioblastoma

  Genomic heterogeneity of glioblastoma (GBM) is suspected to contribute to the poor response to therapy of this disease. We compared molecular characteristics between primary GBM, neurospheres and orthotopic xenograft models derived from the same parental tumor. Driver alterations were in majority propagated from tumor to model systems. Extrachromosomal amplifications of MET, a proto-oncogene coding for a receptor tyrosine kinase, were detected in three primary GBM, largely discarded in neurospheres cultures, but resurfaced in xenografts. The clonal dynamics inferred by somatic single nucleotide variants (sSNVs) in MET-amplified samples diverged from the pattern delineated by the MET amplification event suggesting that the MET event and sSNVs were inherited in different manners. Our analysis shows that extrachromosomal elements are able to drive tumor progression.

  Study EGAS00001001878

• Facial Skin Biophysical Multi-Parameter and Microbiome-Based Korean Skin Cutoype (KSC) Determination

  In this study, we conducted an integrated analysis of skin measurements, clinical BSTI surveys, and the skin microbiome of 950 Korean subjects to examine the ideal skin microbiome-biophysical association. By utilizing four skin biophysical parameters, we identified four distinct Korean Skin Cutotypes (KSCs) and categorized the subjects into three aging groups based on their age distribution. We established strong connections between 15 core genera and the four KSC types within the three aging groups, revealing three prominent clusters of the facial skin microbiome. Together with skin microbiome variations, skin tone/elasticity distinguishes aging groups while oiliness/hydration distinguishes individual differences within aging groups. Our study provides prospective reality data for customized skin care based on the microbiome environment of each skin type.

  Study EGAS00001007334

• Whole exome sequencing in RVOT patients

  In a patient with right ventricular outflow tract (RVOT) tachycardia we identified a heterozygous point mutation in the selectivity filter of the stretch-activated K2P potassium channel TREK-1 (KCNK2 or K2P2.1). This mutation introduces abnormal sodium permeability to TREK-1 In addition, mutant channels exhibit a hypersensitivity to stretch-activation, suggesting that the selectivity filter is directly involved in stretch-induced activation and desensitization. Increased sodium permeability and stretch-sensitivity of mutant TREK-1 channels may trigger arrhythmias in areas of the heart with high physical strain such as the RVOT. We present a pharmacological strategy to rescue the selectivity defect of the TREK-1 pore. Our findings provide important insights for future studies of K2P channel stretch-activation and the role of TREK-1 in mechano-electrical feedback in the heart.

  Study EGAS00001002319

• Low frequency and rare coding variation contributes to multiple sclerosis risk

  Multiple sclerosis is a common, complex neurological disease, where almost 20% of risk heritability can be attributed to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that the majority of the remaining heritability is also due to the additive effects of individual variants, rather than epistatic interactions between these variants, or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that as much as 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common variant signals, which highlight a key role for regulatory T cell homeostasis and regulation, IFNγ biology and NFκB signaling in MS pathogenesis.

  Study EGAS00001003195

• High-resolution structural genomics reveals new therapeutic vulnerabilities in glioblastoma

  We investigated the role of 3D genome architecture in instructing functional properties of glioblastoma stem cells (GSCs) by generating the highest-resolution 3D genome maps to-date for this cancer. Integration of DNA contact maps with chromatin and transcriptional profiles identified specific mechanisms of gene regulation, including individual physical interactions between regulatory regions and their target genes. Residing in structurally conserved regions in GSCs was CD276, a gene known to play a role in immuno-modulation. We show that, unexpectedly, CD276 is part of a stemness network in GSCs and can be targeted with an antibody-drug conjugate to curb self-renewal, a key stemness property. Our results demonstrate that integrated structural genomics datasets can be employed to rationally identify therapeutic vulnerabilities in self-renewing cells.

  Study EGAS00001003493

• The Precision Medicine in Liver Cancer across an Asia-pacific NETwork (PLANET)

  Hepatocellular carcinoma (HCC) is the 2nd most important cause of cancer deaths in the world. The outcomes of treatment in HCC are poor compared to other common cancers because there are no good systemic therapy drugs. We designed a prospective study that will involve 5 different sites within the established Asia-Pacific Hepatocellular Carcinoma Trials Group to study both the genetics as well as immune profiles of HCC in different ethnicities. In this study, patients will be followed-up and at recurrence the tissues to understand the evolution of disease progression. Here, we presented both the genomic (DNA) and phenotypic (RNA) evolution for the first batch of 56 patients. The detailed findings will be listed in the corresponding publication soon.

  Study EGAS00001003813

• An allele-resolved nanopore-guided tour of the human placental methylome

  The placenta is a temporary organ present during pregnancy that is responsible for coordinating all aspects of pregnancy between the mother and fetus. It has a distinct epigenetic, transcriptomic, and mutational landscape with low levels of methylation, high numbers of transcribed loci, and a high mutational burden relative to somatic tissues. We present this landscape through the application of nanopore sequencing technology to provide a more comprehensive picture of female placental genomics and methylomics along with integrated haplotype-resolved transcriptomic analyses across eight trios. Whole genome sequencing of trios allows robust phasing, permitting comprehensive genome-wide investigation of parent-of-origin methylation and transcription. This enhanced view facilitates identifications of many new differentially methylated regions (DMRs), both conserved and differing between individuals, as well as novel imprinted genes.

  Study EGAS50000001301

• DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded (FFPE) tissues followed by targeted sequencing

  To overcome the challenges of low DNA yields, degraded DNA by formalin fixation and diluted signal of genomic aberrations by non-carcinoma components in the heterogeneous FFPE samples, we isolated pure carcinoma and stromal cells using the DEPArray™ NxT system, a microchip-based digital sorter that allows isolation of pure, homogeneous subpopulations of cells from FFPE samples. We isolated pure carcinoma and stromal cell populations from 12 FFPE tissues, including tissues from 9 primary and metastatic breast cancer and 3 primary ovarian high-grade serous carcinomas. This was followed by a targeted panel for somatic mutation and sCNA analysis (7 samples), subject to cell availability. Mutation analysis was performed successfully in 6/7 samples and somatic mutations were detected in all of them.

  Study EGAS50000001327

• RNA-seq of Glioblastoma stem cells

  Chromatin accessibility discriminates stem from mature cell populations, enabling the identification of primitive stem-like cells in primary tumors, such as Glioblastoma (GBM) where self-renewing cells driving cancer progression and recurrence are prime targets for therapeutic intervention. We show, using single-cell chromatin accessibility, that primary GBMs harbor a heterogeneous self-renewing population whose diversity is captured in patient-derived glioblastoma stem cells (GSCs). In depth characterization of chromatin accessibility in GSCs identifies three GSC states: Reactive, Constructive, and Invasive, each governed by uniquely essential transcription factors and present within GBMs in varying proportions. Orthotopic xenografts reveal that GSC states associate with survival, and identify an invasive GSC signature predictive of low patient survival. Our chromatin-driven characterization of GSC states improves prognostic precision and identifies dependencies to guide combination therapies.

  Study EGAS00001003070

• Clonal heterogeneity leads to secondary resistance in a melanoma patient after adoptive cell therapy with tumor-infiltrating lymphocytes

  Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in melanoma patients, although long-term responses seem restricted to patients with complete remissions. Many patients develop secondary resistance to TIL-ACT but involved mechanisms are unclear. Here, we describe a case of secondary resistance to TIL-ACT likely due to intratumoral heterogeneity and selection of a resistant tumor cell clone via transferred T cells. This is the first case of clonal selection of a pre-existing non-dominant tumor cell clone and demonstrates a new mechanism involved in secondary resistance to TIL-ACT and could potentially change current clinical practice, because it advocates for T cell collection from different tumor sites and analysis of tumor heterogeneity before the treatment with TIL-ACT.

  Study EGAS50000000279

• A single-cell multi-omic atlas of nodal B-cell non-Hodgkin lymphomas

  Nodal B-cell non-Hodgkin lymphomas (B-NHL) are a clinically diverse set of cancers thought to originate from distinct stages of B-cell maturation. To characterize intratumor heterogeneity across B-NHL entities, we performed CITE-Seq (cellular indexing of transcriptomes and epitopes) on 51 lymph node samples including mantle cell lymphoma (MCL, n = 8), follicular lymphoma (FL, n = 12), germinal center (GCB, n = 5) or activated B-cell (non-GCB/ABC, n = 7) diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL, n = 11) tumors, in addition to non-malignant reactive lymph nodes (rLN, n = 8). We also performed 5 prime scRNA-seq with immune receptor profiling for 11 of these samples (2 rLN, 2 MCL, 3 FL, 2 DLBCL, and 2 MZL).

  Study EGAS50000000342

• Exome_sequencing_of_thyroid_disease_in_Val_Borbera

  The Val Borbera is a region characterized by low iodine and high prevalence of thyroid disorders, the commonest endocrine disorders in the general population. About 30% of the participants of the Val Borbera Project were affected by such disorders and were characterized by several parameters, TSH level, anti TPO antibodies, echography, family origin. Individuals with extreme phenotypes were identified and could be clustered based on family origin and genotype. We propose to exome sequence 6 of them, affected with true goiter, at high dept (40-60x) to obtain information on exonic rare variants. Due to the family structure and to the availability of whole genome sequence information on 110 individuals from the isolated population we expect to be able to identify putative causative variants for thyroid disorders that may be studied in the remaining affected individuals.

  Study EGAS00001000344

• 10x genomics single cell RNA-seq and ATAC-seq from 10 pre-menopausal patients fimbriae and ampullary part of the fallopian tube

  The fallopian tube, connecting the uterus with the ovary, is a dynamic organ that undergoes cyclical changes and is the site of several diseases, including serous cancer. Here, we use single-cell technologies to construct a comprehensive cell map of healthy pre-menopausal fallopian tubes, capturing the impact of the menstrual cycle and menopause on different fallopian tube cells at the molecular level. The comparative analysis between pre- and post-menopausal fallopian tubes reveals substantial shifts in cellular abundance and gene expression patterns, highlighting the physiological changes associated with menopause. Further investigations into menstrual cycle phases illuminate distinct molecular states in secretory epithelial cells caused by hormonal fluctuations. The markers we identified characterizing secretory epithelial cells provide a valuable tool for classifying ovarian cancer subtypes.

  Study EGAS50000000628

• Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors

  Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. In order to find novel therapeutic leads for this subgroup of patients, we analyzed 58 such Wilms tumors by exome and transcriptome analysis and validated our findings in larger independent cohorts. Recurrent mutations identified either somatically or in the germline included a hotspot mutation (Q177R) in the homeodomain of SIX1 and SIX2 in tumors with high proliferative potential, mutations in microprocessor genes like DROSHA, DGCR8, DICER1 and DIS3L2, and alterations in IGF2, MYCN, and TP53, the latter being strongly associated with dismal outcome. DROSHA and DGCR8 mutations had a strong effect on miRNA profiles in tumors, which we confirmed in cell lines transfected with mutant DROSHA.

  Study EGAS00001000906

• 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

• A collection of 142 samples used to evaluate the sensitivity and specificity of small-scale variation detection in exome-capture data with a particular focus on indel detection.

  The dataset includes exome sequencing data and 704 Sanger sequencing validations for the 142 samples. The 704 Sanger sequencing validations are comprised of 416 variants and 288 sites known to be negative, including 293 indels and 247 negative indel sites. DNA libraries were prepared from genomic DNA using the Illumina TruSeq sample preparation kit. DNA was fragmented using Covaris technology and the libraries were prepared without gel size selection. Target enrichment was performed in pools of six libraries using the Illumina TruSeq Exome Enrichment kit. The captured DNA libraries were PCR amplified using the supplied paired-end PCR primers. Sequencing was performed with an Illumina HiSeq2000 (v3 flow cell, one pool per lane) generating 2x101-bp reads. Technology – Illumina HiSeq 2000

  Study EGAS00001001332

• Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome

  Patients with short QT syndrome (SQTS) may present with syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain less than 25% of SQTS cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene in two unrelated families with SQTS. The mutation causes reduced surface expression of AE3 and reduced membrane bicarbonate transport. Slc4a3 knockdown in zebrafish causes increased cardiac pHi, short QTc, and reduced systolic duration, which is rescued by wildtype but not mutated SLC4A3. Mechanistic analyses suggest that an increase in pHi and decrease in [Cl-]i shortened the action potential duration. However, other mechanisms may also play a role. Altered anion transport represents a mechanism for development of arrhythmia and may provide new therapeutic possibilities.

  Study EGAS00001002632

• Chromosome Y Philogeny in Sardinia

  Genetic variation within the male specific portion of the Y chromosome (MSY) can clarify the origins of contemporary populations, but previous studies were hampered by partial genetic information. Population sequencing of 1,204 Sardinian males identified 11,763 MSY single nucleotide polymorphisms (SNPs), of which 6,751 have not previously been observed. We constructed a MSY phylogenetic tree containing all main haplogroups found in Europe along with many Sardinian-specific lineage clusters within each haplogroup. The tree was calibrated with archaeological data from the initial expansion of the Sardinian population ~7,700 years ago. The ages of nodes highlight different genetic strata in Sardinia and reveal presumptive timing of coalescence with other human populations. We calculate a putative age for coalescence of ~180-200,000 years ago, consistent with previous mitochondrial DNA (mtDNA) based estimates.

  Study EGAS00001000532

• Relaxed selection during a recent human expansion

  To better understand and quantify the effect of a recent expansion process on the amount and pattern of mutation load, we screened the ascending genealogies of 3916 individuals from the CARTaGENE cohort (Awadalla et al. 2013) that were linked to the BALSAC genealogical database (http://balsac.uqac.ca/). Using stringent criteria on the quality of genealogical information, we selected (front) individuals whose ancestors were as close as possible to the front of the colonization of Quebec, and (core) individuals whose ancestors were as far as possible from the front. We then sequenced these 102 individuals at very high coverage (mean 89.5X, range 67X-128X) for 106.5 Mb of exomic and UTR regions and contrasted their genomic diversity to detect if sites with various degrees of conservation and deleteriousness had been differentially impacted by selection.

  Study EGAS00001001957

• Multiple migrations to the Philippines during the last 50,000 years

  A key link to understand human history in Island Southeast Asia is the Philippine archipelago and its poorly investigated genetic diversity. We collected and analyzed the most comprehensive set of population-genomic data for the Philippines, 1028 individuals covering 115 indigenous communities. We demonstrate that the Philippines were populated by at least five waves of human migration. The Cordillerans migrated into the Philippines prior to the arrival of rice agriculture, where some remain to be the least admixed East Asians carrying an ancestry shared by all Austronesian-speaking populations; thereby challenging an exclusive Out-of-Taiwan model of joint farming-language-people dispersal. Altogether, our findings portray Philippines as a crucial gateway, with a multilayered history, that ultimately changed the genetic landscape of the Asia-Pacific region.

  Study EGAS00001005083

• Germline SDHB-inactivating mutation in gastric spindle cell sarcoma (HIPO-021)

  Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Inactivating mutations or epigenetic deregulation of succinate dehydrogenase complex (SDH) genes are considered defining features of a subset of GIST occurring in the stomach. Based on comprehensive molecular profiling and biochemical analysis within a precision oncology program, we identified hallmarks of SDH deficiency (germline SDHB-inactivating mutation accompanied by somatic loss of heterozygosity, lack of SDHB expression, global DNA hypermethylation, and elevated succinate/fumarate ratio) in a 40-year-old woman with undifferentiated gastric spindle cell sarcoma that did not meet the diagnostic criteria for other mesenchymal tumors of the stomach, including GIST. These data reveal that the loss of SDH function can be involved in the pathogenesis of non-GIST sarcoma of the gastrointestinal tract.

  Study EGAS00001004277

• Egyptref: An integrated personal and population-based Egyptian genome reference

  North African individuals are not represented in current genetic data sets. To address this issue, we generated an integrated personal and population-based Egyptian genome reference called Egyptref. Towards this end, we performed a human de novo assembly of an Egyptian individual using long PacBio reads (99x genome coverage) and polished it using Illumina short reads (90x). Variants were phased using 10x Genomics linked reads (80x). This personal genome was complemented with whole genome sequencing-based variant data of 109 further Egyptians and mitochondrial haplogroups from mtDNA sequencing of 326 further Egyptians (of which 100 individuals from EGAD00001001372/EGAD00001001380) to obtain a population-based genome. We used Egyptref for assessing the impact of genetic variation, e.g. by integration of blood RNA sequencing data of the assembly individual.

  Study EGAS00001004303

• The coding and non-coding transcriptional landscape of subependymal giant cell astrocytomas

  Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the central nervous system TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to the impaired circulation of cerebrospinal fluid resulting in hydrocephalus and raised intracranial pressure in patients with TSC. Currently, surgical resection and mTORC1 inhibitors are the recommended treatment options for patients with SEGA. Here, we performed RNA-Seq and small RNA-Seq on SEGAs (n=19) and periventricular controls (n=8) to gain a better understanding of the underlying molecular basis of SEGAs, so that novel treatment targets could be identified.

  Study EGAS00001003787

• Profiling_heterogeneity_in_Human_derived_IPSC_neurons

  The impact of genetic variants on molecular pathways that give rise to neurodegenerative diseases such as Alzheimer’s and Parkinson’s is best elucidated in the appropriate cell types and molecular contexts. Existing studies have focused on bulk profiling of mixed cell types, but have ignored assaying genetic effects across development and cell differentiation. At the core of this proposal is the idea to use single-cell assays to study genetic effects during differentiation of dopaminergic and cortical neurons to identify the sequence of molecular events from variants to healthy and diseased cell states in a cell-specific manner. 1) 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 please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001002885

• Peripheral immunoprofiling of stratifies COVID-19 patients based on disease-specific neutrophil signatures

  The SARS-CoV-2 pandemic has led to increasing numbers of COVID-19 patients all over the world. Aetiopathologies range from no symptoms, mild flu-like to severe cases succumbing to respiratory failure. Reports on a dysregulated immune system in the severe cases, showing similarities to cytokine release syndrome, calls for better characterization and understanding of the changes in the immune system as well as their variance across COVID-19 patients in order to be able to design according to host-directed therapies. Here, we profiled blood transcriptomes of 39 COVID-19 patients and 10 control donors. Enriched granulocyte signatures in whole blood samples were verified in granulocyte samples from 49 COVID-19 patients in a second cohort.

  Study EGAS00001004503

• Profiling of childhood neuroblastoma and the immune microenvironment by single-cell sequencing of RNA and TCR

  Neuroblastoma tumor cells and their tumor microenvironment are studied by single-cell RNA sequencing of primary neuroblastoma tumors and neuroblastoma-infiltrated tissues/metastases. Both diagnostic samples, taken pre-treatment and samples taken after induction chemotherapy at surgical resection and biopsies from relapse samples are included.  For a number of patients single-cell RNA sequencing of blood samples (controls) are included and additionally we performed single-cell T cell receptor sequencing (TCR) on the tumor and blood samples. With this study, we will focus on identifying differences in tumor cells and their (immune) microenvironment 1) before and after treatment or at relapse and 2) between primary tumors and infiltrated tissues/metastases. Moreover, with TCR sequencing we aim to unveil immune cell dynamics in patients with neuroblastoma.

  Study EGAS00001006823

• Germline variant analysis in childhood AML

  Analysis of rare germline variants in childhood AML in a large panel of cancer predisposition genes (n=216) compiled from literature review, and including genes involved in familial hematological malignancies (HM) and bone marrow failure (BMF) syndromes. The prevalence of extremely rare variants in the combined childhood AML cohort (n=72) was compared to that in the Medical Genome Reference Bank (MGRB; n=2570) comprising individuals aged at least 70 years with no history of cardiovascular disease, dementia or cancer. This showed a significant increase of rare alleles in childhood AML for 100% of subset comparisons. Next additional stringent filtering was applied to determine predicted damaging germline predisposition variants. Overall, 21% of the Australian cohort and 25% of the TARGET cohort presented germline variants predicted to be damaging predisposition variants.

  Study EGAS00001006276

• Pathogenic variants damage cell compositions and single cell transcription in cardiomyopathies

  Pathogenic variants in genes that cause dilated (DCM) and arrhythmogenic cardiomyopathies (ACM) convey high risks for the development of heart failure (HF) through unknown mechanisms. Using single nucleus RNA sequencing (snRNAseq), we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, non-ischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene expression at single cell resolution. Together these data illuminate both shared and distinct cellular and molecular architectures of human HF and suggest novel candidate therapeutic targets.

  Study EGAS00001006374