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• Whole exome and targeted DNA sequencing data for formalin-fixed paraffin embedded tissue from de novo small cell prostatic carcinoma cases

  This dataset consists of 44 compressed paired fastq files, 15 of which are generated from whole exome sequencing, and 29 of which are generated from DNA sequencing using a targeted gene panel capturing the exonic regions of 73 prostate cancer driver genes. Targeted DNA sequencing was performed on an Illumina MiSeq (v3 600 cycle kit), and exome sequencing was done using an Illumina HiSeq 2500 (v4 250 cycle kit) machine. The fastq files are named in accordance with the sample aliases provided, which reflect the pathology of interest to this study (small cell prostatic carcinoma--SCPC), whether it was sequenced using an exome or targeted gene panel, whether the FFPE sample was sourced from tumor or benign tissue (labeled T or B, respectively), and whether there exists multiple samples belonging to a single patient.

  Dataset EGAD00001004139

• Multi-omics identify falling LRRC15 as a COVID-19 severity marker and persistent pro-thrombotic signals in convalescence

  Patients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. Here, we perform longitudinal blood sampling of ESKD haemodialysis patients with COVID-19, collecting samples pre-infection, serially during infection, and after clinical recovery. Using plasma proteomics, and RNA-sequencing and flow cytometry of immune cells, we identify transcriptomic and proteomic signatures of COVID-19 severity, and find distinct temporal molecular profiles in patients with severe disease. Supervised learning reveals that the plasma proteome is a superior indicator of clinical severity than the PBMC transcriptome. We show that a decreasing trajectory of plasma LRRC15, a proposed co-receptor for SARS-CoV-2, is associated with a more severe clinical course. Strikingly, we observe that two months after the acute infection, patients still display dysregulated gene expression related to vascular, platelet and coagulation pathways, including PF4 (platelet factor 4), which may explain the prolonged thrombotic risk following COVID-19.

  Study EGAS00001006778

• The Celiac Gene Expression Data Access Committee

  This study presents RNA sequenced from several intestinal phenotypes such as from patients with damaged intestinal mucosa as well as from those without a damaged intestine but still an autoantibody response to tissue transglutaminase (“potential celiac disease”) or those with treated celiac disease. By combining phenotypes in a much larger number of tissue samples from both peripheral blood and mucosal biopsies, we found highly differentially expressed genes, but also identify genes involved in controlling and triggering celiac disease associated changes. This study identifies molecular mechanisms involved in celiac disease and new possible targets for treatment and for identification of individuals at risk.

  Dac EGAC50000000630

• Comprehensive copy number aberration analysis using digital Multiplex Ligation-dependent Probe Amplification (digitalMLPA) in pediatric B-cell precursor acute lymphoblastic leukemia

  In this study a next-generation sequencing based method was applied to comprehensively screen for recurrent, disease-relevant copy number aberrations in a cohort of Hungarian patients. Diagnostic bone marrow samples from 260 children with B-cell acute lymphoblastic leukemia as well as 72 control samples and were investigated by digital multiplex ligation-dependent probe amplification using the disease-specific D007 probemix. Whole chromosome gains and losses, as well as subchromosomal copy number aberrations were simultaneously profiled.

  Dataset EGAD00001010878

• Adenoma development in familial adenomatous polyposis and MUTYH‐associated polyposis: somatic landscape and driver genes

  Familial adenomatous polyposis (FAP) and MUTYH‐associated polyposis (MAP) are inherited disorders associated with multiple colorectal adenomas that lead to a very high risk of colorectal cancer. The somatic mutations that drive adenoma development in these conditions have not been investigated comprehensively. In this study we performed analysis of paired colorectal adenoma and normal tissue DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from each patient.

  Dataset EGAD00001004332

• ECM-free patient-derived organoids preserve diverse prostate cancer lineages and uncover in vitro-enriched cell types

  Patient-derived organoids (PDOs) hold promise for modeling various cancers, yet their application in prostate cancer (PCa) has been limited due to low culture success and the predominance of non-tumor-like cells. Using 164 PCa samples and optimizing culture conditions, we demonstrate that an extracellular matrix (ECM)-free culture method improves PDO take-rates, fostering cell populations with luminal and PCa-specific characteristics. Single-cell RNA sequencing (scRNA-seq) reveals that these ECM-free PDOs closely mirror their original tumors at the transcriptomic level and maintain a diverse array of tumor cell types, unlike traditional Matrigel-based cultures which predominantly yield benign-like cells. This study introduces a PCa PDO single-cell atlas, providing a valuable resource for advancing prostate cancer research.

  Study EGAS50000000807

• Genomic Analysis of Low Grade B-Cell Lymphoma

  We included tumors from 64 newly diagnosed or untreated Low Grade B-Cell Lymphoma (LGBCL) patients, consisting of SMZL (n = 48), NMZL (n = 6), EMZL (n = 2), LPL (n = 5), and B-NOS (n = 3) in this study. Samples were selected from cases consented to the Molecular Epidemiology Resource (MER) of the University of Iowa and Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). RNA or DNA were extracted from 64 frozen LGBCLs tumors (with available matched germline DNA for N=61. For RNA sequencing, library preparation was done using the Illumina TruSeq RNA Exome Kit and sequenced with 100 nucleotide paired-end reads using the HiSeq 4000. For WES, library preparation was done using the Agilent SureSelect XT kit and sequenced with 100 nucleotide paired-end reads using the Illumina HiSeq 4000.

  Study phs002552

• Genetic data of a monozygotic twin pair discordant for ALS

  We performed whole exome sequencing of a monozygotic twin pair discordant for ALS. This dataset contains two VCF files: one of the healthy twin and one of the ALS twin. Library was prepared according to Agilent SureSelectQXT Kit protocol and processed using Illumina NextSeq 550 sequencer). Fastq files were aligned on the reference human genome hg19 (GRCh37) and, for each patient, a list of variations in a VCF format file (Variant Call Format) was produced by GATK software and annotated by wAnnovar.

  Dataset EGAD50000001329

• imputed_bacterial_meningitis

  This study includes 1146 samples of host genotyping data (imputed) from Illumina Omni arrays, using https://imputation.sanger.ac.uk/ with the Haplotype Reference Consortium v1.1. Samples were collected from adults (>16 yrs) patients with CSF confirmed bacterial meningitis in the Netherlands between 2006 and 2015. Metadata includes patient outcome, species of bacteria, and for 467 samples a link to an ENA run with the associated bacterial genome (S. pneumoniae only).

  Dataset EGAD00010002327

• Pheno-seq profiles of single clonal tumor spheroids derived from a patient with colorectal cancer

  Pheno-seq is a new approach that integrates high-throughput imaging and transcriptomic profiling of clonal spheroids/organoids to dissect functional tumor cell heterogeneity in 3D cell culture systems. The method is based on the iCELL8 technology (TakaraBio) that uses barcoded nanowells and a micro-solenoid valve dispenser. The CRC_spheroid dataset contains demultiplexed RNA-sequencing profiles (FASTQ file format, NextSeq 500) of 95 clonal tumor spheroids derived from a patient with colorectal cancer.

  Dataset EGAD00001004131

• IL-10 signalling and macrophage gene expression (2019-08-28)

  Study to stimulate WT and IL-10RB mutant macrophages with LPS in presence or absence of recombinant IL-10 and compare their gene expression profiles by RNASeq These data are 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/ . This dataset contains all the data available for this study on 2019-08-28.

  Dataset EGAD00001005300

• Somatic mutations reveal embryonic genetic bottlenecks generating placental mosaicism

  The human placenta harbours chromosomal aberrations that are absent from the fetus in one to two percent of pregnancies. This confined mosaicism suggests that embryonic genetic bottlenecks exist, which phylogenetically segregate placental tissue. Here, we studied the somatic genetic landscape of human placentas by whole genome sequencing of 86 placental biopsies and of 106 microdissections.

  Dataset EGAD00001006337

• The Haplotype-Resolved Genome and Epigenome of the Aneuploid HeLa Cancer Cell Line

  The genomic architecture of HeLa remains largely unexplored beyond its karyotype, partly because like many cancers, its extensive aneuploidy renders such analyses challenging. We carried out haplotype-resolved whole-genome sequencing of the HeLa CCL-2 strain, examined point- and indel-mutation variations, mapped copy-number variations and loss of heterozygosity regions, and phased variants across full chromosome arms. We also investigated variation and copy-number profiles for HeLa S3 and eight additional strains. We find that HeLa is relatively stable in terms of point variation, with few new mutations accumulating after early passaging. Haplotype resolution facilitated reconstruction of an amplified, highly rearranged region of chromosome 8q24.21 at which integration of the human papilloma virus type 18 (HPV-18) genome occurred and that is likely to be the event that initiated tumorigenesis. We combined these maps with RNA-seq and ENCODE Project data sets to phase the HeLa epigenome. This revealed strong, haplotype specific activation of the proto-oncogene MYC by the integrated HPV-18 genome approximately 500 kilobases upstream, and enabled global analyses of the relationship between gene dosage and expression. These data provide an extensively phased, high-quality reference genome for past and future experiments relying on HeLa, and demonstrate the value of haplotype resolution for characterizing cancer genomes and epigenomes. Reprinted from Adey et. al. 2013, Nature, with permission from Nature Publishing Group.

  Study phs000642

• Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer

  Our study provides insight into molecular alterations in HN tissues within the affected breast and offers a greater understanding of the spatial implications of these aberrations. This was achieved by performing a comprehensive analysis of RNA sequencing data and proteomic profiles from breast cancers (n=19) and their matched HN tissues (n=38), healthy breast from cosmetic reduction mammoplasty (RM; n=5), and risk reducing mastectomies (RR, n=5), with peritumoral samples excised at proximal (TP, <2 cm) and distal (TD, 5-10 cm) sites from the primary tumor.

  Study EGAS00001004510

• Clonal_analysis_Bcell_activation

  We developed a B cell stimulation protocol that allowed us to expand a smaller number of naive B cells in culture (2,000 B cells at day 0). On day 6, we performed single-cell RNA-and BCR-sequencing on the entire culture, preserving both clonal diversity and size.

  Dataset EGAD50000002114

• Melanoma transcriptomic data from patients undergoing immunotherapy

  This dataset contains raw RNA sequencing data from melanoma patient tumor samples collected before and during immunotherapy. The data support investigation of treatment-related changes in tumor cell populations. Samples were analyzed as part of a study exploring cellular responses to immune-based therapies.

  Dataset EGAD50000001569

• scRNA-seq of bronchoalveolar lavage (BAL) samples from patients with severe COVID-19 to assess dexamethasone response in the lungs

  Single-cell RNA-sequencing of bronchoalveolar lavage (BAL) samples from patients with severe COVID-19 with or without Dexamethasone treatment and for responders and non-responders was performed using 10x Genomics technology.

  Dataset EGAD50000000292

• Clones derived from early passage tumoroids of colorectal cancer

  We obtained different clones from early passage CRC tumoroids to study mutational signatures specific for truncal or private somatic alterations. These whole genome sequences are part of a larger study on the heterogeneity and evolution of DNA mutation rates in microsatellite-stable colorectal cancer.

  Dataset EGAD50000000152

• CONTAGIOUS trial - COVID-19 16S dataset

  16S amplicon data of nasopharyngeal swabs in a COVID-19 cohort recruited at UZ Leuven. The dataset contains a single experiment, comprising 150 runs corresponding to 125 unique samples. Runs comprise paired fastq files (2*250 bases) obtained from an Illumina MiSeq instrument.

  Dataset EGAD00001006864

• Metagenomic sequencing of fecal samples from celiac disease patients and controls

  150 nt paired-end metagenomic shotgun sequencing (Illumina HiSeq 2000) of fecal samples from 130 (mostly treated, i.e. adhering to gluten-free diet) celiac disease patients and 106 controls from the CeDNN cohort from the University Medical Center Groningen, The Netherlands. For six celiac disease patients, data from two timepoints (before and during gluten-free diet) are included, resulting in a total of 242 samples. The dataset includes 2 encrypted fastq files per sample (.fq.gz.c4gh) en sample phenotypes (.txt.c4gh).

  Dataset EGAD50000001397

• Stanford Acute Myeloid Leukemia Single-Cell DNA Sequencing

  These are single-cell DNA sequencing data from acute myeloid leukemia samples from Stanford University. They were used in multiple publications to understand clonal evolution in AML.

  Study phs003853

• Correlative Studies for Protocol #14-C-0059: T Cells Expressing an Anti-GD2 Chimeric Antigen Receptor in Patients with GD2+ Solid Tumors, a Collaboration with CIMAC-CIDC

  This study is a retrospective correlative analysis of immune cell phenotypes in samples from a Phase I clinical trial (NCT02107963) of GD2 CAR-T cells (GD2-CAR.OX40.28.z.iC9) in children and young adults with osteosarcoma and neuroblastoma. The study was a 3+3 dose-escalation study with four dose levels (1 x 10(5) transduced T cells/kg; 1 x 106 transduced T cells/kg; 3 x 106 transduced T cells/kg; and 1 x 107 transduced T cells/kg). Apheresis and final manufactured GD2 CAR-T product samples were analyzed by bulk RNA sequencing and ATAC sequencing. The patients were stratified into good CAR-T expanders (peak CAR-T expansion >1000 GD2 CAR copies/100ng DNA) and poor CAR-T expansion (peak CAR-T expansion Increased naïve T cell subsets in baseline apheresis are associated with patients who experienced good CAR T cell expansion A T cell exhaustion signature was observed in the manufactured GD2 CAR-T product and may have contributed to lack of efficacy observed in this trial Increased myeloid-derived suppressor cell (MDSC) signatures were observed in patients with poor CAR-T expansion CAR-T product in good expanders displayed increased AP-1 factor transcription factor motifs, such as BATF, JUN, and FOS Data provided in dbGaP for this study include: Bulk RNA-Seq data for 11 pre-treatment peripheral blood and 11 GD2 CAR-T product from 14 patients. ATAC sequencing of 22 peripheral blood samples and 5 GD2 CAR-T products from 14 patients.

  Study phs003455

• Whole exome sequence analysis in multiple system atrophy

  To identify a susceptible gene for multiple system atrophy, exome sequence analysis was conducted in 14 patients and 7 controls.

  Study JGAS000009

• Aurora US Metastatic Breast Cancer Retrospective Project

  The AURORA US Metastatic Breast Cancer project is funded by the Breast Cancer Research Foundation (BCRF) Evelyn H. Lauder Founder's Fund for Metastatic Breast Cancer Research. This multi-center effort conducted within the Translational Breast Cancer Research Consortium (TBCRC) and cancer researchers to better understand the metastatic process through the study of both the primary and metastatic tissue. In the retrospective phase, TBCRC sites submitted matched primary and metastatic tissues and blood from previous collections for piloting the process. Samples were profiled using whole genome DNA sequencing, whole exome DNA sequencing, DNA methylation arrays, and RNA sequencing. The final freeze set for samples with successful nucleic acid extraction and molecular assays included 55 patients with 31 primary tissues and 102 metastases. Twenty patients had tissue collected at autopsy and included 19 with more than one metastasis. Metastases were from 20 different tissue locations with the most common sites being liver, lung, lymph node, and brain. The median age at primary diagnosis was 49 years. The clinical subtypes of the primary tumors were 34% Triple Negative, 30% ER+HER2-, 11% ER+HER2+, and 7% ER-HER2+. Patients received an average of 3 lines of therapy in the metastatic setting. The median overall survival from primary diagnosis was 4.5 years and overall survival from metastatic diagnosis was 2 years.

  Study phs002622

• Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma

  We conducted a randomized phase II study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma (NCT02519322) and assessed clinical responses and immune correlates. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST overall response rate 73%, pathologic complete response rate 45%) but substantial toxicity (73% grade 3 treatment related adverse events), whereas treatment with nivolumab monotherapy yielded modest responses (RECIST overall response rate 25%, pathologic complete response rate 25%) and low toxicity (8% grade 3 treatment related adverse events). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. Mutational load was also higher in responders to therapy.

  Study EGAS00001003178