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• Genetic differences between primary colorectal cancer and its paired synchronous and metachronous metastases

  This study contains data obtained from 210 CRC samples (87 pairs and 36 singletons for whom only one of the sample pair was available). Our sample set consisted of 105 primary tumor and 105 metastatic samples. Data are analysis-ready BAM files. Sequencing libraries were prepared with the SureSelect Human All Exon V8 kit by Agilent. Sequencing was done on NovaSeq X Plus instrument (Illumina, San Diego, CA, USA) using 150-bp paired-end reads.

  Dataset EGAD50000001460

• PanelSeq IDC samples

  PDX samples of breast cancer IDC mouse models created from patient tumor material of the NKI. Genomescan prepared the samples according to the procedure for Hybridization Capture using an Agilent SureSelect custom 0.5-2.9Mb kit. The prepared libraries were sequenced with Illumina sequencing technology. The samples are in fastq format and consist of the following PDX samples: IDC025, IDC026, IDC029, IDC031, IDC032, IDC038, IDC057, IDC062, IDC065, IDC069, IDC072, IDC090B, IDC092, IDC097, IDC099, IDC107, IDC113, IDC117, IDC143, IDC152, IDC159A, IDC159B, IDC180, IDC186, IDC192, IDC197, IDC198, IDC207, IDC209, IDC216, IDC218, IDC222, IDC229, IDC232, IDC274, IDC282, IDC290, IDC299, IDC307, IDC338, IDC344, IDC346, ILC006, ILC012, ILC083 and ILC248.

  Dataset EGAD50000001149

• RNA, ATAC, ChIP datasets from iPSC Derived Macrophages with and without TNFRSF1A intronic deletion using CRISPR

  This dataset consists of functional genomic data from iPSC derived Macrophages with or without CRISPR deletions and controls. It contains 21 paired end fastq files consisting of 6 total RNA-seq samples and 9 ATAC samples, for ChIP there are 2 H3K4me3 samples, 2 H3K27ac samples along with 2 paired input samples. The samples were sequenced on the Illumina HiSeq4000 amd Illumina NextSeq500 platforms.

  Dataset EGAD50000000984

• Facioscapulohumeral muscular dystrophy (FSHD): RNA-seq of isogenic TIRM+, TIRM- muscle and PBMCs from patients and matched controls

  FASTQ files describing paired-end RNA-sequencing of isogenic TIRM+ and TIRM- muscle biopsies from 24 FSHD patients (48 samples) and vastus lateralis muscle biopsies from 11 matched control individuals. FASTQ files are also provided describing RNA-sequencing of 15 FSHD peripheral blood mononuclear samples and 14 matched controls. For muscle biopsies sequencing was at 21.7-35.5 million reads/sample. RNA was extracted from PBMCs followed by globin depletion with sequencing at 19.7-46.5 million reads/sample.

  Dataset EGAD00001011077

• National Heart, Lung, and Blood Institute (NHLBI) Data Coordinating Center, Microbiome of the Lung and Respiratory Track, Lung HIV Microbiome Project (LHMP)

  Humans interact with countless microorganisms in multiple environments. The Lung HIV Microbiome Project (LHMP) characterized the microbiome of the lung and respiratory tract. This effort provided initial data to develop further hypotheses addressing differences between HIV-infected and HIV-uninfected individuals. The project involved multiple studies, either single center or multiple-center studies. The research design of each study varies with the objective of that study. The Lung HIV Microbiome Project (LHMP) worked collaboratively to ensure the clinical and scientific integrity and success of this project. The LHMP characterized the microbiome of the lung alone or in combination with the oropharyngeal cavities in HIV-infected individuals and HIV-uninfected controls using molecular techniques to identify bacteria. Knowledge of the lung microbiome and that of other components of the respiratory tract in healthy and diseased states may lead to the identification of predictors of disease progression and therapeutic targets for translation into better preventive and treatment strategies. Study datasets and biospecimens are available for request from https://biolincc.nhlbi.nih.gov/studies/lhmp/.

  Study phs000769

• Cell-type eQTLs for single-cell Mendelian Randomisation

  The following study mapped eQTLs in the post-mortem human brain from snRNA-seq generated on 391 individuals. Following eQTL discovery and identification of state-specific eQTLs (dynamic associations interacting with disease), colocalisation and MR was performed integrating GWAS from 42 traits, for the identification of putatively causal genes with cell-type specific context. This study contains raw sequencing data and genotype for two datasets used in this work; - The MRC 60 dataset, which contains snRNA-seq generated on post-mortem brain from 60 control individuals (104 samples total, split across prefrontal cortex and hippocampus). Samples were pooled into 27 distinct pools, each of which was split across 4 lanes. Following sequencing and mapping using cellranger, demultiplexing was done using Demuxlet using the pool-specific genotype data (which contain sample IDs). - The Roche PD dataset, which is 10X multiome data generated on on 70 PD and 22 control individuals.

  Study EGAS50000000687

• UNC Tumor Donation Program Set 2021

  The goal of this study is to study gene expression patterns in primary, metastatic tumors, and normal tissues.

  Study phs002429

• Type 1 Diabetes Genetics Consortium (T1DGC): Case-only RNA-Seq Study

  Peripheral blood mononuclear cells (PBMC) from 82 T1D cases from the T1DGC study were fractionated by positive selection on magnetic beads into CD4+ T cells, CD8+ T cells and CD19+ B cells. RNA purification, library preparation and sequencing to an average of 50 million reads per sample were performed by the HudsonAlpha Genome Services Laboratory. The resulting dataset includes 82 subjects with data from at least one cell type; sequence data from all 3 cell types is available from 79 subjects. The individuals in this study can be linked to the phs000911 T1DGC ImmunoChip study via subject ids to obtain both genotypic and phenotypic information, including genotypes used for expression quantitative trait locus analysis.

  Study phs001426

• Cancer-Normal chronic myeloid leukaemia sequencing data for "A comparative analysis of algorithms for somatic SNV detection in cancer", Bioinformatics 29 (2013) 2223

  This dataset contains the fastq sequencing data collected from bone marrow DNA of a chronic myeloid leukaemia patient at time of diagnosis.

  Dataset EGAD00001000967

• WGS and WES data for manuscript titled: ctDNA as a biomarker of progression in oesophageal adenocarcinoma

  WGS and WES data for manuscript titled: ctDNA as a biomarker of progression in oesophageal adenocarcinoma

  Dataset EGAD00001008554

• The Genomic Landscape of Juvenile Myelomonocytic Leukemia

  This study analyzed samples from 29 patients with juvenile myelomonocytic leukemia (JMML) using whole exome sequencing. Each patient had a paired germline tissue along with a diagnostic leukemia sample. Germline tissue types included buccal mucosa, cordblood, Epstein-Barr virus immortalized cell lines and fibroblasts from either skin or bone marrow. Leukemia samples were either blood or bone marrow. Seven of the 29 patients also had a relapsed leukemia sample available for exome analysis.

  Study phs000973

• Single cell RNA and ATAC sequencing data from GBM patients

  Glioblastoma cells infiltrate and incorporate into the normal brain parenchyma. We conduct unbiased multimodal single-cell and spatial sequencing to capture GBM cells and the surrounding tumor microenvironment using a regional sampling strategy. For each patient, we profile the peritumoral region, tumor edge, and tumor core, providing a comprehensive characterization of the transcriptional and epigenetic landscape of GBM spatial heterogeneity, with a specific focus on infiltrative cells.

  Study EGAS50000000547

• ABO: a 3D stroma-supported culture platform enabling full human B lymphopoiesis for disease modeling and gene therapy development

  Defective B-cell development underlies a large proportion of inborn errors of immunity, but progress in understanding disease mechanisms and of developing therapies has been limited by inadequate human in vitro models. Here, we establish a 3D aggregate culture platform composed of hematopoietic stem and progenitor cells (HSPCs) and mouse bone marrow stromal cells as an assay for efficient B-cell output (the ABO platform). ABOs supported progression through pro-B, pre-B, immature, and transitional B-cell stages, with a transcriptional profile and B-cell receptor (BCR) repertoire diversity closely resembling human bone marrow B-cell ontogeny. ABO-derived B cells exhibited functional signaling and differentiated into class-switched memory and antibody-secreting B cells following CD40-mediated stimulation. The ABO platform reproduced the arrest in B-cell development observed in RAG1-SCID patient–derived HSPCs, which was corrected by lentiviral RAG1 gene therapy. Thus, ABOs provide a clinically relevant platform for modeling B-cell immunodeficiencies and evaluating therapeutic strategies.

  Study EGAS50000001693

• Data access committee for RNA-seq as a tool for evaluating human embryo competence

  Dac EGAC00001001215

• TARGET Trial Study Cohort

  In a randomized controlled clinical trial, investigators will compare the effects on [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) from two treatment regimens in rheumatoid arthritis (RA) patients deemed methotrexate inadequate responders (MTX-IRs). Two common RA treatments will be compared: triple therapy (sulfasalazine, methotrexate, and hydroxychloroquine) versus tumor necrosis factor (TNF) inhibitor (etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening). Consenting subjects will be screened for eligibility and randomized to a treatment arm. Subjects will be randomized to a treatment arm with either synthetic disease-modifying antirheumatic drugs (DMARDs) [triple therapy: sulfasalazine, methotrexate, and hydroxychloroquine] or biologic DMARDs [etanercept or adalimumab, plus background methotrexate for all subjects and hydroxychloroquine for subjects who were taking this at screening]. Once randomized, a baseline visit will be conducted with each subject. Baseline data collection includes questionnaires, disease activity score, and the first FDG-PET/CT imaging. After the baseline at week 0, subjects will visit with their rheumatologist at weeks 6, 12, 18, and 24 for safety labs and further collection of disease activity scores and questionnaires. The second FDG-PET/CT will be performed at week 24. Blood specimens will be collected at weeks 0, 6, 18, and 24 for bioassays. Subject participation will end after the week 24 visit. Patients and care providers will be unblinded. The FDG-PET/CT image readers will be blinded to treatment arm as well as timepoint of image acquisition.

  Study phs003720

• Distinct evolutionary trajectories of primary high grade serous ovarian cancers revealed through spatial mutational profiling

  High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to emergence of treatment-resistant sub-clones. We sought to measure the degree of genomic diversity within primary, untreated HGSC to examine the natural state of tumor evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on thirty-one spatially and temporally separated HGSC tumor specimens (six patients) including ovarian masses, distant metastases, and fallopian tube lesions. We found widespread intra-tumoral variation in mutation, copy number, and gene expression profiles, with key driver alterations in genes present in only a subset of samples (e.g. PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range: 10.2% to 91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology with common etiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating diversity arises at early stages of tumorigenesis. Our results reveal that HGSC exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug resistance mechanisms.

  Study EGAS00001000547

• Genome-wide analyses of cell-free DNA for therapeutic monitoring of patients with pancreatic cancer

  Determining response to therapy for patients with pancreatic cancer can be challenging. We evaluated methods for assessing therapeutic response using cell-free DNA (cfDNA) in plasma samples from 40 patients with metastatic pancreatic cancer as part of the CheckPAC trial (NCT02866383). Patients were evaluated before and after initiation of therapy using tumor-informed plasma whole-genome sequencing (WGMAF), and genome-wide cfDNA fragmentation profiles and repeat landscapes (ARTEMIS-DELFI). Of those assessed with WGMAF, molecular responders had a median overall survival (OS) of 319 days compared to 126 days for non-responders (HR=0.29, 95% CI=0.11–0.79, p=0.011). For ARTEMIS-DELFI, patients with low scores after therapy initiation had a longer median OS than patients with high scores (233 days versus 172 days, HR=0.12, 95% CI=0.046-0.31, p<0.0001). We validated ARTEMIS-DELFI in a separate cohort of 40 patients with pancreatic cancer who were part of the PACTO trial (NCT02767557). These analyses suggest that non-invasive mutation and fragmentation-based cfDNA approaches can identify therapeutic response of individuals with pancreatic cancer.

  Study EGAS50000000923

• DAC: Antisense long non-coding RNAs are deregulated in skin tissue of patients with systemic sclerosis

  Dac EGAC00001000788

• Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis

  Study EGAS00001006781

• Subset of EGAS00001005112 (The INFORM Precision Medicine Study for High-Risk Pediatric Malignancies, 17 exomes) which is used in EGAS00001005243 (Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B)

  Part of the project: The INFORM Precision Medicine Study for High-Risk Pediatric Malignancies resulted in the publication of this study: Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B. This dataset contains the subset of 17 patient exome sequencing data.

  Dataset EGAD00001007864

• Cell-type, allelic and genetic signatures in the human pancreatic beta cell transcriptome

  Pancreatic beta cells within the islets of Langerhans are centrally involved in the pathogenesis of both type 1 and type 2 diabetes. Describing the differentiated state of the human beta cell has been hampered so far by technical (low resolution microarrays) and biological limitations (whole islet preparations rather than isolated beta cells). We circumvent these by deep RNA sequencing of purified beta cells from 11 individuals, presenting here the first characterization of the human beta cell transcriptome. Additionally, we perform the first comparison of gene expression profiles between beta cells, whole islets (N=7) and beta cell depleted islet preparations (N=5), revealing thus beta cell specific expression signatures. Finally, we combine this with whole-genome sequencing data for 7 of our donors, describing here the first set of genetic variants controlling inter-individual variability in beta cell gene expression.

  Study EGAS00001000442

• SSBP1 sample

  The dataset includes exome sequencing results for a patient with SSBP1 mutations that cause a complex optic atrophy spectrum disorder

  Dataset EGAD00001005475

• GSA QCed data

  QC-ed data of 9,534 DDD Study participants, including 8,879 individuals with inferred GBR ancestry. Details of genotype QC can be found in https://www.medrxiv.org/content/10.1101/2023.04.20.23288860v1.full.pdf. Genome builds are indicated in the file name. Related individuals have not been removed. Of the 9,534 samples there are 3,148 mothers, 3,138 fathers and 3,248 probands, which form 3,099 trios. Of the 8,879 GBR samples, there are 2,931 mothers, 2,937 father and 3,011 probands, which form 2,788 trios. Most of the probands have been previously genoyped on the llumina HumanCoreExome BeadChip (EGAD00010001598) or the Illumina InfiniumCoreExome Beadchip (EGAD00010001600). All samples were genotyped on the Illumina Global Screening Array.

  Dataset EGAD00010002568

• Multicenter AIDS Cohort Study (MACS)

  The Multicenter AIDS Cohort Study (MACS) - now part of the MACS-WIHS Combined Cohort Study (MWCCS) investigates the epidemiology of human immunodeficiency virus (HIV) infection among men who have sex with men. Over 7,000 participants volunteered for semiannual interview, physical examination, and laboratory testing across the 325 years of the study, in four metropolitan areas of Los Angeles, Chicago, Baltimore/Washington (DC) and Pittsburgh. The study aimed to identify risk factors for occurrence and clinical expression of the HIV infection, and to establish a repository of biologic specimens for future study. Study visits included detailed questions covering HIV-related symptoms and utilization of health services, demographic and psychosocial characteristics, a quality of life survey, a physical examination, a detailed form on medications used as prophylaxis and/or treatment, a neuropsychological screening and examination, blood samples to do measure hematologic variables including enumeration of T-cell subsets and HIV viral load and evaluate genetic risk factors via genome wide association studies using data generated using the Infinium Multi-Ethnic Global BeadChip genotyping array in all participants. Men who have sex with men, with and without HIV infection were enrolled in the MACS. MACS data continues to be available through the merged MWCCS cohort.

  Study phs002226

• Characterizing Advanced Breast Cancer Heterogeneity and Treatment Resistance through Serial Biopsies and Comprehensive Analytics

  This dataset accompanies the manuscript "Characterizing Advanced Breast Cancer Heterogeneity and Treatment Resistance Through Serial Biopsies and Comprehensive Analytics". In this study we discuss the clinical implications and consequences of molecular heterogeneity in a metastatic breast cancer patient identified through serial biopsies, multi-omic analysis, and longitudinal patient monitoring, performed through the precision oncology program, Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART). This case study describes a metastatic breast cancer patient with a highly heterogenous tumor that began as ER positive/HER2 negative on diagnosis, then was found to be ER negative/HER2 positive in a metastatic liver lesion (Study biopsy #1), and finally triple negative (TNBC) in another metastatic liver biopsy (Study biopsy #2). Multi-omic assays included clinical genomic panel sequencing, clinical immunohistochemistry, a clinical protein profiling assay (Intracellular Signaling Protein Profiling), RNA sequencing, and RPPA. Here we provide the expression data from RNAseq and RPPA data on Study biopsy #2 for the patient discussed in this case report. Note: The first liver biopsy did not yield sufficient material for RNAseq or RPPA.Raw RNA FASTQ files from Study biopsy #2 of the liver Gene expression (RNAseq) files from Study biopsy #2Protein expression (RPPA) files (level 2, 3, 4) for Study biopsy #2

  Study phs002321