1248 results for ""halted+early"+"slower-than-anticipated+enrollment"+hospitalized+oral+adaptive+platform"

in 30.33 milliseconds.

• Comparison_of_transcriptional_response_of_induced_pluripotent_stem__iPS__cell_derived_and_monocyte_derived_macrophages_to_bacterial_lipopolysaccharide_stimulation

  In the first part of this project, we will differentiate IPS cells from 5 human donors into macrophages, and extract RNA from unstimulated and LPS stimulated macrophages to perform RNA sequencing. We will also extract RNA before and after stimulation in blood- derived macrophages from 5 additional, unrelated healthy samples. In the second part of the project, RNA-seq data will be analysed to compare LPS response of these two macrophage populations. In summary, we will perform 75bp PE RNA-seq on 20 samples (10 pre and post stimulus), on the HiSeq 2500 platform. Samples will be multiplexed at 5 samples / lane, so we will require 4 flow cells in total.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 EGAS00001000563

• Pilot study for Illumina TST170 NGS panel on cutaneous T cell lymphoma samples

  A number of genomic studies using next generation sequencing (NGS) techniques have attempted to understand the underlying genetic basis of cutaneous T-cell lymphoma and found alterations in genes that are involved in T-cell activation, NF-kB and JAK-signal transducer and activator of transcription (STAT) pathways. 8 diagnostic skin biopsy samples (2xplaque, 6xtumour) on FFPE blocks were selected from 8 MF patients (stage IB:n=1, IIB:n=6, IVA2:n=1). An H&E was performed in order to assess percentage of tumor cells, viable cells, necrosis and immune infiltration, to determine the number of slides required for NGS. Freshly cut unstained slides were manually macrodissected prior to DNA and RNA extraction. Targeted deep sequencing was performed using panel of 170 genes associated with common solid tumours (Illumina TruSight Tumour 170 NGS panel). VCF files generated via the Illumina’s Basespace platform.

  Study EGAS00001002567

• Cancer and germline exomes consisting of FASTQ paired-end reads from melanoma and lung cancer samples

  Efforts to precisely identify tumor human leukocyte antigen presented peptides (HLAp) capable of mediating T cell based tumor rejection still face important challenges. Recent reports suggest that non-canonical cancer HLAp could be immunogenic but their identification requires highly sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches. Here, we present a MS-based analytical pipeline that can precisely characterize the non-canonical HLAp repertoire, incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLAp. Albeit often at low levels and in distinct subpopulations of cells, numerous non-canonical HLAp are shared across tumors. This analytical platform holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.

  Study EGAS00001003723

• RNA-seq consisting of FASTQ paired-end reads from cancer samples

  Efforts to precisely identify tumor human leukocyte antigen presented peptides (HLAp) capable of mediating T cell based tumor rejection still face important challenges. Recent reports suggest that non-canonical cancer HLAp could be immunogenic but their identification requires highly sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches. Here, we present a MS-based analytical pipeline that can precisely characterize the non-canonical HLAp repertoire, incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLAp. Albeit often at low levels and in distinct subpopulations of cells, numerous non-canonical HLAp are shared across tumors. This analytical platform holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.

  Study EGAS00001003724

• VIKING Health Study - Shetland

  The Viking Health Study – Shetland, together with ORCADES collectively termed VIKING, aims to identify genes influencing risk factors for common diseases such as heart disease, diabetes, glaucoma and stroke. The genetic research cohort study in Shetland was established to identify genetic variants, both common and rare, increasing risk of disease. This isolated population has a number of characteristics, the most important being the very large number of distant relatives, which are favourable for the identification of rare variants influencing disease risk. This study describes PCR-free paired end whole genome sequencing (TruSeq DNA PCR-Free, Illumina) run on a HiSeqX platform at 30X coverage on 500 individuals from VIKING. Unrelated individuals from the largest families were selected first, followed by those from smaller families, until eventually related individuals were selected to best represent the variation in the full cohort.

  Study EGAS00001003872

• An exome sequencing approach to defining the genetic risk factors for Achilles tendinopathy

  Musculoskeletal soft tissue injuries are complex phenotypes. Case control association studies using the candidate gene approach have predominantly been used to identify risk loci for these injuries. However, the ability to identify all risk conferring variants using this approach alone is unlikely. Therefore, this study aimed to define the genetic profile of these injuries using whole exome sequencing and a customized analysis pipeline. The exomes of ten exemplar asymptomatic controls and ten exemplar cases with Achilles tendinopathy were individually sequenced using a platform that included the coverage of the untranslated regions and miRBase miRNA genes. These results provide a proof of concept for the use of a customized pipeline for the exploration of a larger genomic dataset. This approach, using previous research to guide a targeted analysis of the data has generated new genetic signatures in the biology of musculoskeletal soft tissue injuries.

  Study EGAS00001003234

• POPCOL: population-based colonoscopy.

  PopCol is a cohort study in Stockholm, Sweden that includes a data-rich set of individuals with data available from bowel symptoms questionnaires, gastroenterology visits and biospecimens (genotype and 16S sequencing from blood and stool samples, respectively). Genotyping was carried out using the Illumina HumanOmniExpressExome-8v1 arrays at the SciLifeLab NGI facility in Uppsala, Sweden. Fecal DNA was extracted from samples kept at -80°C using Qiagen 5 QIAamp DNA Stool Mini Kits and analyzed using 16S rRNA gene amplicon sequencing (in the V1-V2 hypervariable region). This was performed on the Illumina MiSeq platform at the Institute of Clinical Molecular Biology (IKMB) in Kiel, Germany. Of these, six PopCol participants were PPI users and 12 used antibiotics. The study was approved by the local Committee of Research Ethics (Forskningskommitté Syd) at Karolinska Institutet, Stockholm, in November 2001. Written informed consent was obtained from all participants

  Study EGAS00001004869

• Identification of neoantigen from MSI-CRC patient derived organoids and its application for targeting by autologous T cells

  Targeting neoantigens expressed only by tumor cells enable tumor destruction without unexpected damages to healthy tissues. Here, we identified neoantigens from microsatellite instable (MSI) colorectal cancer (CRC) patient-derived organoids by genomics and immunopeptidomics approches. The neoantigens in this study were predicted from frame-shift mutation by whole-genome sequencing and confirmed its presentation on organoids surface class I HLA molecules by mass spectrometry. We utilized these neoantigens to isolate neoantigen-specific CD8 T cells from autologous PBMC, and proved tumor organoids killing ability of the CD8 T cells, whereas it did not attack normal organoids. This study provides a platform to identify neoantigen from patient-derived cancer organoids and a model to validate T cell recognition, which could be useful for adoptive CD8 T cell transfer treatment for MSI-CRC patient.

  Study EGAS00001006633

• Digital tEchnology For Lung Cancer Treatment

  The aim of the DEFLeCT project (Digital tEchnology For Lung Cancer Treatment) is to generate a technological platform for precision medicine in order to set predictive personalised algorithms for patient diagnosis and therapy. All resectable patients having histologically confirmed stage IB-IIIA non-small cell lung cancer(NSCLC) will be enrolled in the PROMOLE study, a related and ongoing observational prospective clinical study, for tissue sampling. A large biobank of lung cancer samples and the corresponding healthy tissues and biological components (ie, blood, stools, etc.) with complete clinical, pathological and molecular information will be collected. The project will lay the basis of a knowledge hub and qualified technology aimed not only at answering the medical and scientific community's questions, but also meant to be useful to individual patients by predicting the response to adjuvant and second-line drugs in case of relapse of the disease.

  Study EGAS00001007219

• MediMer: A versatile do-it-yourself peptide-receptive MHC class I multimer platform for tumor neoantigen-specific T cell detection

  Peptide-loaded MHC class I (pMHC-I) multimers have revolutionized our capabilities to monitor disease-associated T cell responses with high sensitivity and specificity. To improve the discovery of T cell receptors (TCR) targeting neoantigens of individual tumor patients with recombinant MHC molecules, we developed a peptide-loadable MHC class I platform termed MediMer. MediMers are based on soluble disulfide-stabilized β2-microglobulin/heavy chain ectodomain single-chain dimers (dsSCD) that can be easily produced in large quantities in eukaryotic cells and tailored to individual patients’ HLA allotypes with only little hands-on time. Upon transient expression in CHO-S cells together with ER-targeted BirA biotin ligase, biotinylated dsSCD are purified from the cell supernatant and are ready to use. We show that CHO-produced dsSCD are free of endogenous peptide ligands. Empty dsSCD from more than 30 different HLA-A,B,C allotypes, that were produced and validated so far, can be loaded with synthetic peptides matching the known binding criteria of the respective allotypes, and stored at low temperature without loss of binding activity. We demonstrate the usability of peptide-loaded dsSCD multimers for the detection of human antigen-specific T cells with comparable sensitivities as multimers generated with peptide-tethered β2m-HLA heavy chain single-chain trimers (SCT) and wild-type peptide-MHC-I complexes prior formed in small-scale refolding reactions. Using allotype-specific, fluorophore-labeled competitor peptides, we present a novel dsSCD-based peptide binding assay capable of interrogating large libraries of in silico predicted neoepitope peptides by flow cytometry in a high-throughput and rapid format. We discovered rare T cell populations with specificity for tumor neoepitopes and epitopes from shared tumor-associated antigens in peripheral blood of a melanoma patient including a so far unreported HLA-C*08:02-restricted NY-ESO-1-specific CD8+ T cell population. Two representative TCR of this T cell population, which could be of potential value for a broader spectrum of patients, were identified by dsSCD-guided single-cell sequencing and were validated by cognate pMHC-I multimer staining and functional responses to autologous peptide-pulsed antigen presenting cells. By deploying the novel CHO producer cell-based dsSCD MHC-I MediMer platform, we hope to significantly improve success rates for the discovery of personalized neoepitope- specific TCR in the future by being able to also cover rare HLA allotypes.

  Study EGAS50000000065

• Single-cell RNA-seq of immune cells from human tumor fragments after 48 hour culture ex vivo (Kaptein et al., 2024)

  Single-cell RNA-seq profiling of immune cells from human ovarian carcinoma, renal carcinoma and melanoma samples after 48h of ex vivo culture using the patient-derived tumor fragment platform (5 samples total). Samples were cultured in various conditions, including: untreated, CD8-IL2v-treated, CD8-IL2v + LCKi -treated, aPD1-treated, CD8-IL2v + aPD1 -treated, Untargeted IL2-treated, aCD3-treated and aCD3 + CD8-IL2-treated . FASTQ files contain gene expression data, feature barcode antibody capture or TCR data on immune cells from all conditions combined per patient.

  Dataset EGAD50000000377

• HCC cfMeDIP-seq

  This dataset comprises 406 raw fastq files derived from 203 plasma cfDNA samples from 90 patients diagnosed with hepatocellular carcinoma (HCC). The samples include 90 baseline HCC (b-HCC) samples, collected during liver transplant or resection surgeries, and 113 postoperative follow-up (f-HCC) samples. For each sample, 10ng of cfDNA was used for library preparation utilizing cfMeDIP-seq technology based on the 5mC antibody-immunoprecipitation strategy. Libraries were validated via Bioanalyzer trace analysis and sequenced on Illumina NovaSeq 6000 or HiSeq 2500 platform with paired-end 150-bp (NovaSeq) or 125-bp (HiSeq) model for ~100 million reads per sample.

  Dataset EGAD50000000651

• scRNA-seq dataset, RCC

  scRNA-seq dataset for the study "Surgery in combination with immune checkpoint therapy as an effective treatment for patients with metastatic cancer." The dataset comprises 38 samples from 19 patients, with each pair includes a baseline (BL) sample and a post-biopsy or post-surgery sample. Each sample corresponds to an R1 (read 1) and an R2 (read 2) files (.fastq.gz) for paired reads. Beside procedure (biopsy or surgery), another important phenotype is response (PR and PD in this case, no SD for these patients), included in the description of the samples. The sequencing was performed using Illumina NovaSeq 6000 platform., as seen in the experiment description.

  Dataset EGAD50000000566

• Dataset of scRNAseq from 56 CRC, treatment-naive and post-chemotherapy

  The dataset includes FASTQ source files of scRNA-seq for 56 CRC patients, sequenced with Illumina 10x platform. All patients were diagnosed with colorectal cancer between 2014 and 2022 at the Gustave Roussy Institute. Cohort includes 32 samples from untreated patients and 24 samples from patients who received chemotherapy. Chemotherapy included FOLFOX or FOLFIRI as first line, in some cases in combination with anti-VEGF or anti-EGRF drugs (avastin, bevacizumab or cetuximab) as the second and third lines. The post-treatment cohort included 18 responders (partial response, stable disease and complete response) and 6 progressors (progressive disease).

  Dataset EGAD50000001218

• scRNA transcriptome and TCR sequencing data modeling treatment responses in eight renal cell carcinoma patient

  Single cell RNA sequencing and coupled TCR sequencing data generated following immunological treatments in patient-derived ex vivo tumor models. Dataset consist of 46 sequencing samples originating from eight individual patient-derived ex vivo models. Single cell RNA and TCR sequencing data is generated using 10X Genomics platform with 5´ sequencing. The submission contains 46 Fastq files where each patient-derived ex vivo model and it's transcriptomic response to specified treatment is a unique sequencing run. TCR sequencing runs are submitted as one file per individual model, gathering all the treatment conditions.

  Dataset EGAD50000001934

• Identification of cell type differences in FOXN1 mutation carriers by scRNA-seq

  scRNA-seq was performed on the BD Rhapsody platform. CD45+ lymphocytes from two FOXN1het patients and one cord blood sample as control were sorted from frozen cryopreserved samples. The samples were split and each sample was stained with 4 Sampletag antibodies before Abseq staining with the BD Immune Discovery panel and 6 additional antibodies was performed to better classify immune cell subsets. The sorted and stained populations were pooled before loading onto the BD Rhapsody cartridge. The manufacturer's protocol was followed for library construction and samples were sequenced on an Illumina NovaSeq 6000.

  Dataset EGAD50000001708

• 10X single-cell Multiome (RNA+ATAC) and single-cell RNAseq of xenograft-derived HSPC, progenitors and myeloid progeny

  10X genomics chromium single-cell ATAC+RNA (Multiome) was use to prepare single-nucleus RNA- and ATAC-seq libraries for human HSPC sorted from xenografts recovered from inflammatory challenge. 10X genomics 3' kits were used to prepare single-cell RNA-seq libraries for committed progenitors and myeloid cells from the same xenografts. These were sequenced on an Illumina NovaSea 6000 platform; BAM files are provided. Samples from 3 conditions were sequenced for each cell type; 3 chromatin accessibility runs and 9 gene expression runs are provided.

  Dataset EGAD50000002328

• Genomic Variant Dataset of 5,309 Jeju Residents: Integrated WGS and SNP Array Analysis

  This dataset comprises genomic data from the Jeju Genome Project (JGP). WGS libraries were prepared using TruSeq Nano DNA kits and sequenced on Illumina NovaSeq 6000, with variants called via the DRAGEN Germline pipeline (v4.0.3). Genotyping was performed using the customized Axiom_JPMI v1 Chip on the Affymetrix GeneTitan platform. Raw data were processed using APT (v2.11.4), followed by phasing with Eagle (v2.4.1) and imputation via Minimac3 (v2.0.1) using a JGP-specific reference panel to optimize accuracy for the Jeju population.

  Dataset EGAD50000002451

• Donor InSight III study: Participants typed during UK Biobank version 2 array development phase

  The Donor InSight III study, undertaken by Sanquin research, recruited 3,046 Dutch blood donors between 2015 and 2016. The purpose of the study was to gain more insight into characteristics of donors, their motivations and health. All participants were at the time of recruitment active blood donors. Genotyping data was produced using the Thermo Fisher Scientific Axiom Genotyping platform. The UK Biobank version 2 array design was used, content on this array has been added to allow for accurate DNA based identification of human blood group antigens.

  Dataset EGAD00001005026

• Deciphering Intratumoral Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma with a Radiogenomics Platform

  We used 200 ccRCC samples from 51 tumors to simultaneously isolate DNA, RNA, and protein according to established protocol. RNA quality was assessed using an Agilent Bioanalyzer, and total RNA with RIN>7 was used for further RNA sequencing. 184 ccRCC samples from 49 tumors passing initial quality control underwent RNA sequencing at Admera Health Inc. (Genohub Inc., Austin, TX). RNA sequencing libraries were prepared using the Illumina TruSeq Stranded mRNA high throughput (HT) sample preparation kit following the manufacturers’ protocol. Pair-end RNA Seq data was deposited in this cohort.

  Dataset EGAD00001005356

• Transcriptome profiling of three giant cell tumour of bone (GCTB) cell lines

  This dataset contains RNA-seq data of giant cell tumour of bone (GCTB) cell lines (n=3). Cell lines consist of neoplastic "stromal" cells harboring a heterozygous H3F3A p.G34W mutation. RNA-seq was performed on the BGISEQ-500 platform (PE100) and uploaded data contains fastq files, vcf files, and gene expression values (TPM). Cell lines, data generation, and data analysis are described in the following publication: Venneker et al., Histone deacetylase inhibitors as a therapeutic strategy to eliminate neoplastic “stromal” cells from giant cell tumors of bone, 2022.

  Dataset EGAD00001009074

• Whole exome sequencing of atypical 3q26 samples

  The Genomic DNA Clean & Concentrator kit (ZYMO Research) was used to remove EDTA from the DNA samples. Sample libraries were prepared using 100 ng of input according to the KAPA HyperPlus Kit (Roche) using Unique Dual Index adapters (Integrated DNA Technologies, Inc.). Exomes were captured using the SeqCap EZ MedExome (Roche Nimblegen) according to SeqCap EZ HyperCap Library v1.0 Guide (Roche) with the xGen Universal blockers – TS Mix (Integrated DNA Technologies, Inc.). The amplified captured sample libraries were paired-end sequenced (2x100 bp) on the Novaseq 6000 platform (Illumina) and aligned to the hg19 reference genome using the Burrows-Wheeler Aligner (BWA).

  Dataset EGAD00001006102

• COMPARE study: participants typed during UK Biobank version 2 array development phase

  The COMPARE study enrolled 29,066 British blood between donors between February 2016 and March 2017, the study aim is to find the optimum technology for haemoglobin screening (ISRCTN 90871183). All participants were at the time of recruitment active blood donors. The 4,796 participants in this dataset have consented to join the NIHR BioResource. Genotyping data was produced using the Thermo Fisher Scientific Axiom Genotyping platform. The UK Biobank version 2 array design was used, content on this array has been added to allow for accurate DNA based identification of human blood group antigens.

  Dataset EGAD00001005023

• High-Coverage Whole-Exome Sequencing Identifies Candidate Genes for Suicide in Victims with Major Depressive Disorder

  In this study, we applied an Illumina HighSeq platform-based high-coverage WES technique, which, in addition to the exons, allows the determination of 5′- and 3′-UTRs, promoters to a certain length, along with off-target sequences, such as introns, intergenic regions and infecting viruses. Brains from suicide victims (n = 23; 15 males and eight female) who had suffered from major depressive disorder and from control participants (n = 21; 14 males and seven females) who had died from other causes were used for whole-exome sequencing. Alignment files in bam format were uploaded.

  Dataset EGAD00001004082

• RNA-seq of iPSC-derived hepatocyte-like cells

  We performed RNA-seq on polyA-enriched mRNA isolated from the original liver biopsy tissue (Liver tissue), primary liver cells (PLC), hepatocyte-like cells (HLCs) differentiated from induced pluripotent stem cells (iPSCs), and iPSCs. RNA libraries were prepared using the Illumina TruSeq Stranded mRNA Sample Preparation protocol (ref. RS-122-2101, Illumina, San Diego CA, US) and sequenced using the Illumina HiSeq2500 platform following the manufacturer’s protocol. Samples were sequenced in paired-end mode to a length of 2x76 base pairs. Images from the instrument were processed using the manufacturer’s software to generate FASTQ sequence files.

  Dataset EGAD00001003770

• Tumor and normal exomes for 95 PMBCL cases

  Whole-exome sequencing for 95 PMBCL cases (including 21 with matching normal DNA) was performed using a targeted capture approach with the SureSelect Human All Exon V6+UTR bait (Agilent Technologies) followed by massively parallel sequencing of enriched fragments on the HiSeq2500 platform (Illumina). Five libraries were pooled per lane and a 125bp paired-end mode was used. Tumor and normal DNA samples were sequenced to an average of 115X (SD 24X). All reads were aligned to the human reference genome (hg19) using bwa-mem version 0.7.5a29 with optical and PCR duplicates removed using the Picard tool.

  Dataset EGAD00001005780

• CCA WGS data (16 CCA with matched normal, 4 cell-line)

  Fastq files for WGS for 16 CCAs (with matched normal tissues), and 4 cell lines in an AA-treatment experiment (0, 10, 20, 40ug AA treatment after 180 days; 2 runs each for 10ug and 40ug experiments). Genomic DNA was extracted using DNeasy Blood and Tissue Kit (Qiagen). Sequencing libraries were prepared from DNA extracted using the SureSelect XT2 Target Enrichment System for the Illumina Multiplexed Sequencing platform (Illumina) according to the manufacturer’s instructions. Whole genome sequencing was performed on Illumina HiSeq4000 sequencer with paired-end sequencing.

  Dataset EGAD00001012100

• Genetics and Functional Studies of Autosomal Recessive Neurological Disorders

  Neurological conditions account for over 6% of the global disease burden. There are more than 600 neurological disorders, and cognitive dysfunction, also referred to as intellectual disability (ID), occupies a prominent position in this list. Cognitive dysfunction arises from the failure of neuronal cells to organize into a complex network and remodel this network in response to learning and experience. It is manifested by deficits in adaptive behaviors in everyday social and practical skills. Due to its high prevalence and the lifetime cost of care per individual, in the range of $1-2 million in United Sates (CDC), it presents a significant health burden. Genetic and functional studies of the genes and protein determinants of ID have helped to elucidate the molecular pathways of human brain development in health and disease. However, the identity of a large number of essential molecular and cellular components still remain elusive. The objectives of our study are to expand the genetic repertoire of causal ID genes and characterize their role in neuronal structure and cognitive function. The rationale is that identification and functional elucidation of causative gene variants that lead to cognitive dysfunction will be essential for understanding brain function and for developing improved diagnostic tools and efficacious preventive and therapeutic agents for neurological disorders, including ID. There are 3 aims of our comprehensive research program: 1) Ascertain and clinically phenotype members of extended families segregating autosomal recessive intellectual disability (ARID); 2) identify new ARID genes and gene products; and 3) determine the functions of prioritized novel ARID genes using multifaceted approaches, including analysis of spatiotemporal expression patterns in mouse brain, targeting in cultured rat hippocampal neurons, effects on cell morphology and synapse abundance, synaptic transmission and plasticity in neuronal cells by electrophysiology and live-cell imaging assays. The project will advantageously combine human clinical assessment, genetic and functional analyses relevant to brain development and function. Impact: Execution of the proposed studies will generate new knowledge that is clinically relevant, with high potential to impact ID molecular diagnosis, prognoses, and identify novel therapeutic targets to slow progression, delay onset, and possibly devising precision medicine approaches for ID.

  Study phs003298

• METABRIC

  The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (CNVs, SNPs) and acquired somatic copy number aberrations (CNAs) were associated with expression in 40% of genes, although the landscape was dominated by cis and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP, and MAP2K4. Unsupervised analysis of paired DNA/RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, ER-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration 0152hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the 0152CNA-devoid sub-group and a Basal-specific chromosome 5 deletion-driven mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic copy number aberrations on the transcriptome.

  Study EGAS00000000083

• Innate and Adaptive Immunity in Parkinson Disease-P20

  Increasing evidence supports the role of brain and systemic inflammation in the etiology of Parkinson disease (PD). We used gene expression profiling (RNA-seq) to examine the activation state of peripheral blood monocytes in 18 patients with early, untreated PD and 16 healthy control (HC) subjects. Monocytes were isolated by negative selection, and gene expression studied by RNA-seq and gene set enrichment analysis. A computational model that incorporated case/control status, sex, and the interaction between case/control status and sex was utilized. We found that there was a striking effect of sex on monocyte gene expression. There was inflammatory activation of monocytes in females with PD, with enrichment of gene sets associated with interferon gamma stimulation. In males, the activation patterns were more heterogeneous. These data point to the importance of systemic monocyte activation in PD, and the importance of studies which examine the differential effects of sex on pathophysiology of the disease.

  Study phs002063

• Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer

  Mismatch repair (MMR) deficient cancer evolves through the continuous erosion of coding homopolymers in target genes. Curiously, the MMR genes MSH6 and MSH3 also contain coding homopolymers and these are frequent mutational targets in MMR-deficient cancers. The impact of incremental MMR mutations on MMR-deficient colorectal cancer evolution is unknown. We show that microsatellite instability modulates DNA repair by toggling hypermutable mononucleotide homopolymer runs in MSH6 and MSH3 through stochastic frameshift switching. Spontaneous mutation and reversion modulates subclonal mutation rate, mutation bias, and clonal HLA and neoantigen diversity. Patient-derived organoids corroborate these observations and show that in the absence of immune selection MMR homopolymer sequences drift back into reading frame, suggesting a fitness cost of elevated mutation rates. Combined experimental and simulation studies demonstrate that subclonal immune selection favours incremental MMR mutations. Overall, our data demonstrate that MMR-deficient colorectal cancers fuel intratumour heterogeneity by adapting subclonal mutation rate and diversity to immune selection.

  Study EGAS50000000297

• Resuscitation Outcomes Consortium (ROC) Trauma Epidemiologic Registry (Trauma Epistry) (ROC-Trauma Epistry-BioLINCC)

  Data Access NOTE: Please refer to the "Authorized Access" section below for information about how access to the data from this accession differs from many other dbGaP accessions.Available Data: This dataset only includes traumatic injury participants. For ROC cardiac arrest Epistry data please see: ROC-Cardiac Epistry 1 and 2 and ROC-Cardiac Epistry 3.Objectives: To build a prospective population-based registry of participants with out-of-hospital traumatic injury responded to by Emergency Medical Services (EMS). Specific aims included: to establish whether the results of Resuscitation Outcomes Consortium (ROC) trials can be generalized to the larger population of people that experience traumatic injury; to more fully establish the burden of traumatic injury; and to examine the relationships between variation in EMS structure and process, regional and periodic factors, and participant outcomes.Background: Traumatic injury is a major public health problem generating substantial morbidity, mortality, and economic burden on society. The majority of seriously injured persons are initially evaluated and cared for by prehospital providers, however the effect of EMS systems, EMS clinical care, and EMS interventions on trauma patient outcomes is largely unknown. EMS factors such as service level, number of responding providers, use of procedures or drugs in the field, training, quality assurance/feedback, and response time intervals also vary significantly by region.The Resuscitation Outcomes Consortium (ROC) was established in 2004 to conduct clinical research in the areas of cardiopulmonary arrest and life-threatening traumatic injury with the overall goal of improving resuscitation outcomes. Previous trauma registries have generally focused primarily on hospitalized patients with limited prehospital information. Registries may also exclude trauma cases at far ends of the spectrum, such as those who die in the field or in a non-trauma center and/or patients that are treated and released. These limitations do not allow for detailed, outcome-based assessments of EMS system factors necessary to define prehospital resuscitation best practices. Therefore there was a need for standardized data collection of out-of-hospital traumatic injuries matched to hospital-based outcomes in diverse geographic locations in order to identify the independent effects of prognostic or treatment factors accounting for variations in survival. Participants: The registry included 13,830 traumatic events from 264 EMS agencies transporting to 287 acute care hospitals from the following regional centers: Birmingham, Alabama; Dallas, Texas; Iowa City, Iowa; Milwaukee, Wisconsin; Pittsburgh, Pennsylvania; Portland, Oregon; San Diego, California; Seattle/King County, Washington; Ottawa, Ontario; Toronto, Ontario; and Vancouver, British Columbia.Design: ROC Epistry collected standardized data regarding episode-specific factors, participant demographics, clinical information, pre-hospital interventions and disposition, hospital information, and participant outcome for all out-of-hospital traumatic injuries in the ROC regions. Cases were identified through review of emergency response system records including dispatch centers, EMS ground agencies, and air medical services. Out-of-hospital data were extracted from existing databases whenever possible and augmented with targeted review of EMS reports. Hospital data were abstracted directly from the hospital file in most cases. Sites submitted data using a web-based interface or batch uploads (Newgard, et al., 2008, PMID: 18482792).

  Study phs003809

• HeartShare - Extant Datasets - Harmonized Clinical Trials Collection

  Heart failure with preserved ejection fraction (HFpEF) prevalence is rising with an aging population and contributing comorbidities, such as obesity and diabetes. The Get With The Guidelines - Heart Failure (GWTG-HF) study showed that the proportion of hospitalized HFpEF patients rose from 2005 to 2010, and this trajectory continued to increase through 2020. HFpEF patients have a poor 5-year outcome with a 75% mortality rate. Taken together, these data suggest that HFpEF may be the dominant HF subtype in the future, affecting approximately 1 in 10 adults during their lifetime.In addition to its increasing prevalence, HFpEF is a heterogeneous syndrome with multiple pathophysiological processes and varied clinical presentations. There is an urgent need to improve understanding of different HFpEF phenotypes to match patients with interventions based on their unique subtype. Phenomapping studies have identified between two and six HFpEF clusters/phenogroups with shared features. Of these, three overlapping phenotypes repeatedly arise: an 'older, vascular aging' phenotype, 'metabolic, obese' phenotype, and 'relatively younger, natriuretic peptide (NP) deficiency' phenotype. Continued refinement of these HFpEF subtypes is needed to identify distinct characteristics and underlying biologic and molecular mechanisms towards therapeutic development and future precision trials with improved diagnostic criteria and treatment including prevention.The HeartShare extant datasets collection consists of selected completed trials on HFpEF which have been harmonized for the purpose identifying and defining subtypes. The goal is to identify HFpEF subtypes that have a common pathophysiology. Through the HeartShare extant datasets collection, users can request access to both the harmonized data and the individual trial datasets.To request access to this study collection, select phs003989 in the dbGaP when submitting a data access request. The following clinical trials and harmonized data is available through this collection:Study NameHandleAccessionConsent GroupsSurgical Treatment for Ischemic Heart FailureBioLINCC_STICHphs003493.v1.p1GRUHeart Failure Network Aldosterone Targeted Neurohormonal Combined with Natriuresis TherapyBioLINCC_HFN_ATHENAphs003506.v1.p1GRUHeart Failure Network - Effectiveness of Ultrafiltration in Treating People With Acute Decompensated Heart Failure and Cardiorenal SyndromeBioLINCC_HFN_CARRESSphs003510.v1.p1GRUHeart Failure Network: Diuretic Optimization Strategies Evaluation in Acute Heart FailureBioLINCC_HFN_DOSEphs003524.v1.p1GRUHeart Failure Network - Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure PatientsBioLINCC_EXACT_HFphs003533.v1.p1GRUHeart Failure Network: Functional Impact of GLP-1 for Heart Failure TreatmentBioLINCC_HFN_FIGHTphs003542.v1.p1GRUHeart Failure Network - Nitrate's Effect on Activity Tolerance in Heart Failure with Preserved Ejection FractionBioLINCC_HFN_NEATphs003548.v1.p1GRUHeart Failure Network - Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart FailureBioLINCC_HFN_RELAXphs003565.v1.p1GRUHeart Failure Network - Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of DyspneaBioLINCC_HFN_ROSEphs003589.v1.p1GRUHeart Failure: A Controlled Trial Investigating Outcomes of Exercise TrainingBioLINCC_HF_ACTIONphs003599.v1.p1HMBHeart Failure: A Controlled Trial Investigating Outcomes of Exercise TrainingBioLINCC_HF_ACTIONphs003599.v1.p1HMB-NPUGuiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart FailureBioLINCC_GUIDE_ITphs003621.v1.p1GRUSudden Cardiac Death in Heart Failure TrialBioLINCC_SCD_HeFTphs003654.v1.p1GRUTreatment of Preserved Cardiac Function Heart Failure With an Aldosterone AntagonistBioLINCC_TOPCATphs003665.v1.p1HMB-MDSHeart Failure Network - Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEFBioLINCC_HFN_INDIEphs003667.v1.p1GRUStudies of Left Ventricular DysfunctionBioLINCC_SOLVDphs003668.v1.p1GRUEvaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization EffectivenessBioLINCC_ESCAPEphs003782.v1.p1GRU

  Study phs003989

• Genome-wide genotyping data and exome sequencing of 100 European-descent and 100 African-descent Belgians used in the EGAS00001001895 study

  The 100 European-descent (EUB) and 100 African-descent (AFB) Belgians studied were genotyped for a total of 4,301,332 SNPs on the Illumina HumanOmni5-Quad BeadChips. Whole-exome sequencing was carried out for the same 200 individuals with the Nextera Rapid Capture Expanded Exome kit, on the Illumina HiSeq 2000 platform, with 100-bp paired-end reads. This kit delivers 62 Mb of genomic content per individual, including exons, untranslated regions (UTR), and microRNAs. Omni5 and exome datasets were merged, yielding a concordance rate between platforms of 99.93%.

  Dataset EGAD00010001131

• Single-cell RNA sequencing of blood immune cells before and after interleukin-2 immunotherapy

  Single-cell RNA sequencing of flow cytometry sorted human CD45+ immune cells from 3 systemic lupus erythematosus patients (SLE_002, SLE_004, and SLE_006) collected at baseline (day 0, before interleukin-2 immunotherpay) and day 5 (after 1 treatment cycle of interleukin-2 immunotherapy). Sorted immune cells were hash tagged and then stained with TotalSeq Human Universal Cocktail (Biolegend) before further processing for single-cell RNA sequencing using the 10X-Genomics platform. Samples from all 3 patients were pooled and loaded on 3 lanes of the chromium controller, resulting in 1 raw sequncing file for each lane.

  Dataset EGAD50000000662

• Phenotype information

  This study explores the cell-free transcriptome in a humanized DLBCL patient-derived tumor xenograft (PDTX) model. Blood plasma samples (n=171) derived from a DLBCL PDTX model in-cluding 27 humanized (HIS) PDTX, 8 HIS non-PDTX and 21 non-HIS PDTX non-obese diabetic (NOD)-scid IL2Rgnull (NSG) mice were collected during humanization, xenografting, treatment, and sacrifice. The mice were treated with either rituximab, cyclophosphamide, doxorubicin, vincris-tine, and prednisone (R-CHOP), CD20-targeted human IFNα2-based AcTaferon combined with CHOP (huCD20-Fc-AFN-CHOP), or phosphate-buffered saline (PBS). RNA was extracted using the miRNeasy serum/plasma kit and sequenced on the NovaSeq 6000 platform using the using the SMARTer Stranded Total RNA-Seq Kit v3.

  Dataset EGAD50000000806

• Single cell RNAseq and TCRseq data from tumor and blood samples from 4 patients with muscle invasive bladder cancer

  For this dataset we performed single cell RNAseq paired with single cell TCR-seq on tumor and blood samples from 4 patients. This dataset contains 4 tumor samples as well as 4 blood samples. Each sample is made up of 2 sets of paired fastq files. The first pair contains reads corresponding to RNA transcripts (_Transcripts in file name), while the second pair contain reads corresponding to TCRs (_VDJ in file name). Sequenced on the Illumina NovaSeq6000 platform in a paired-end run using an SP flow cell (v1.5, 300 cycles).

  Dataset EGAD50000001381

• MorphoITH: A Framework for Deconvolving Intra-Tumor Heterogeneity Using Tissue Morphology

  The ccRCC-ITH study WES dataset is derived from a morphology guided multi-regional sequencing dataset used to study the relationship between morphology and genetic evolution. It contains whole exome sequencing data of 18 tumor and 2 adjacent normal samples from 2 UTSW patients, who have consented to depositing their genomic data to public repository. Tumor samples come from different tumor sites, including primary tumor, thrombus and metastases. WES was performed using 75bp paired-end fragments at an average read depth > 50x on a NovaSeq 6000 platform (Illumina, San Diego, CA, USA). The raw data is in fastq format.

  Dataset EGAD50000001550

• scRNAseq data of human innate lymphoid cells (ILCs) and natural killer (NK) cells from fresh umbilical cord blood

  scRNA-seq was performed on the BD Rhapsody platform. ILCs (ILC1, ILC2, ILC3) and NK cells were bulk sorted from fresh cord bloods of 3 donors. The 4 samples containing ILCs and NK cells from each donor were stained with Sampletag antibodies (12 samples in total) before Abseq staining with the BD Immune Discovery panel and 6 additional antibodies was performed to better classify immune cell subsets. The sorted population were pooled before loading onto the BD Rhapsody cartridge. The manufacturer's protocol was followed for library construction and samples were sequenced on a Illumina NovaSeq 6000.

  Dataset EGAD50000001713

• WES Profiles from the CheckMate-577 Clinical Trial

  The dataset contains WES profiles of 396 patients from the CheckMate-577 (CA209-577) clinical trial whose ICF allows data deposition into a public repository. The Allprep DNA/RNA FFPE kit was used to simultaneously purify genomic DNA and total RNA from formalin-fixed, paraffin embedded (FFPE) tissue sections. DNA was analyzed by Whole Exome Sequencing using Swift Biosciences Accel-NGS 2S Hyb DNA Library Kit for library preparation and hybridization using Agilent SureSelect All Exon v6, followed by sequencing on the Illumina NovaSeq platform with a 100bp paired-end strategy and a target read depth of 100M per tumor sample. Fastq files are included.

  Dataset EGAD50000002395

• EstMB cohort participants sequenced with MGISEQ-2000 platform

  Ensuring the comparability of data generated across different sequencing platforms has become a pressing concern in efforts to uncover robust links between the microbiome and human health. In this study, we conducted a comprehensive comparison of taxonomic and functional profiles from matched human gut microbiome sample pairs, sequenced using both the MGISEQ-2000 (MGI) and NovaSeq 6000 (Illumina NovaSeq) platforms.

  Study EGAS50000001538

• Ultra-fast multiplex small DNA sequencing on the MinION nanopore sequencing platform

  Here, we developed an ultra-rapid multiplexed library preparation and sequencing method for the MinION and applied this method to accurately test euploid and aneuploid genomic DNA samples in under three hours, including library preparation and sequencing. This novel method shows great promise as a clinical diagnostic test for applications requiring rapid short-read DNA sequencing.

  Study EGAS00001002650

• Mutational analysis of an oligoprogressive sarcomatoid hepatocellular carcinoma treated with an immune checkpoint inhibitor.

  The dataset is composed of three sequenced tumor samples: (I) Meta-bone-557 (bone metastasis obtained from occipital lesion resection during treatment with Liposomal doxorubicin); (II) Meta-CNS-888 (brain metastasis obtained from surgical resection during treatment with Nivolumab); (III) Primary-liver-463 (primary hepatic tumor obtained from surgical resection during treatment with Nivolumab). Genomic DNA from tumor samples was extracted using GeneRead DNA FFPE kit (Qiagen), containing Uracyl-D Glycosylase, according to the manufacturer’s instructions. Whole-exome libraries were prepared using SureSelect XT Clinical Research Exome Target Enrichment kit (Agilent Technologies # 5190-7338). Sequences (150bp paired-end) were generated on a NextSeq 500 sequencing platform (Illumina).

  Dataset EGAD00001006982

• Whole exome sequencing of normal CD34+ cells

  The Genomic DNA Clean & Concentrator kit (ZYMO Research) was used to remove EDTA from the DNA samples. Sample libraries were prepared using 100 ng of input according to the KAPA HyperPlus Kit (Roche) using Unique Dual Index adapters (Integrated DNA Technologies, Inc.). Exomes were captured using the SeqCap EZ MedExome (Roche Nimblegen) according to SeqCap EZ HyperCap Library v1.0 Guide (Roche) with the xGen Universal blockers – TS Mix (Integrated DNA Technologies, Inc.). The amplified captured sample libraries were paired-end sequenced (2x100 bp) on the Novaseq 6000 platform (Illumina) and aligned to the hg19 reference genome using the Burrows-Wheeler Aligner (BWA)3, v0.7.15-r1140.

  Dataset EGAD00001007645

• RNA-seq data from 27 glioblastoma samples

  27 Fresh frozen tissue specimens were crushed by mortar and pestle, homogenized using the QIAShredder kit (Qiagen), and genomic DNA and total RNA were extracted using the AllPrep DNA/RNA Mini kit (Qiagen), according to the manufacturer’s instructions. RNA libraries were synthesized using 200 ng of total RNA using the Ilumina TruSeq Stranded RNA LT Sample Prep Kit (Illumina), and subsequently sequenced on the NextSeq550 platform to a read depth of 80 million clusters and 160 million paired end reads (75 bp X 75 bp) using V2 chemistry.

  Dataset EGAD00001008362

• Genetic architecture of autism spectrum disorder in India

  The dataset consists of whole exome sequencing data (fastq format) of 100 non-syndromic autism spectrum disorder patients from India. Whole exome sequencing data is generated using Agilent SureSelect v6 capture kit and Illumina HiSeq sequencing platform. Paired end fastq files are available.

  Dataset EGAD00001008621

• 3q-capture DNA sequencing of atypical 3q26 cases

  3q-capture DNA sequencing was performed as we described previously 13. In summary, genomic DNA was fragmented using the Covaris shearing device (Covaris), and sample libraries were assembled following the TruSeq DNA Sample Preparation Guide (Illumina). After ligation of adapters and an amplification step, target sequences of chromosomal regions 3q21.1-q26.2 were captured using custom in-solution oligonucleotide baits (Nimblegen SeqCap EZ Choice XL). The design of target sequences was based on the human genome assembly hg19: chr3q21.1:126036241-130672290 - chr3q26.2:157712147-175694147. Amplified captured sample libraries were paired-end sequenced (2x100 bp) on the HiSeq 2500 platform (Illumina) and aligned against the hg19 reference genome using the Burrows-Wheeler Aligner (BWA)25

  Dataset EGAD00001006123

• scRNAseq of aplastic anemia and healthy immune cells co-cultured with autologous HSPCs

  This dataset contains 8 batches of bone marrow or peripheral blood cells of patients with aplastic anemia and bone marrow cells of healthy controls. The samples from different experimental conditions have been multiplexed with Totalseq-C antibodies (feature barcoding). To demultiplex the samples, see instructions in 10.5281/zenodo.2590196 and https://github.com/janihuuh/aa_manu. Each sample is analysed with Chromium V(D)J and 5' Gene Expression Platform v2 (10X Genomics). The raw data includes fastq files for Gene expression, feature barcodes and V(D)J Expression. The processed data have been deposited in the ArrayExpress database at EMBL-EBI (www.ebi.ac.uk/arrayexpress).

  Dataset EGAD00001012120

• Genome-Wide Association Study of Endometrial Cancer in the Epidemiology of Endometrial Cancer Consortium (E2C2)

  Endometrial cancer, the most common gynecological malignancy in the United States, has both an environmental and genetic component. To this end, we conducted a genome-wide association study to identify genes involved in endometrial cancer using studies from the NCI-supported Epidemiology of Endometrial Cancer Consortium (E2C2). For the discovery stage we included samples from 6 cohort and 7 case control studies through 2007. The total number of cases genotyped were 2,307, white women of European descent, and 2,307 matched controls using the Illumina HumanOmniExpress platform. We conducted the replication using the Infinium HumanExome BeadChip, which successfully genotyped 177,139 variants in 1055 cases and 1778 controls from four ethnically diverse studies that are part of the Epidemiology of Endometrial Cancer Consortium (E2C2). The overall goal is to determine whether certain genotypes are predictive of future endometrial cancer risk, and whether the genotypes interact with established endometrial risk factors.

  Study phs000893

• Prospective Analysis of Genotypes in Adults Undergoing Therapy for Lung Cancer (Paclitaxel Cohort)

  Lung cancer is frequently treated with paclitaxel in combination with several other agents; however, paclitaxel treatment is often ineffective or limited by treatment-related toxicities. Heritable variants in genes associated with absorption, distribution, metabolism, and elimination may predict paclitaxel clinical outcome and toxicity. We designed a prospective multi-institutional study that recruited 546 patients receiving therapy with a 5-year follow up. All patients were genotyped using the Drug Metabolizing Enzymes and Transporters (DMET) platform, which ascertains 1931 genotypes in 235 genes. Genotypes were compared to the progression-free survival of paclitaxel therapy and clinically-significant paclitaxel toxicities. Seven genetic variants were associated with paclitaxel PFS (in ABCB11, ABCC3, ABCG1, CYP8B1, NR3C1, FMO6P, and GSTM3), whereas four genetic variants (in VKORC1, SLC22A14, GSTA2, and DCK) were associated with paclitaxel toxicities. The present SNPs have limited clinical utility but suggest that certain genes are related to important paclitaxel pathways in lung cancer.

  Study phs001660

• Simultaneous Trimodal Single Cell Measurement of Transcripts, Epitopes, and Chromatin Accessibility Using TEA-Seq

  Single-cell measurements of cellular characteristics have been instrumental in understanding the heterogeneous pathways that drive differentiation, cellular responses to signals, and human disease. Recent advances have allowed paired capture of protein abundance and transcriptomic state, but a lack of epigenetic information in these assays has left a missing link to gene regulation. Using the heterogeneous mixture of cells in human peripheral blood as a test case, we developed a novel scATAC-seq workflow that increases signal-to-noise and allows paired measurement of cell surface markers and chromatin accessibility: Integrated Cellular Indexing of Chromatin Landscape and Epitopes (ICICLE-seq). We extended this approach using a droplet-based multiomics platform to develop a trimodal assay that simultaneously measures Transcriptomics (scRNA-seq), Epitopes, and chromatin Accessibility (scATAC-seq) from thousands of single cells, which we term TEA-seq. Together, these multimodal single-cell assays provide a novel toolkit to identify type-specific gene regulation and expression grounded in phenotypically defined cell types.

  Study phs002316

• A Genome-Wide Association Study in Patients Experiencing Drug-Induced Long-QT Syndrome and/or Torsades de Pointes; A Collaboration Between the NIH Pharmacogenomics Research Network and the RIKEN Yokohama Institute Center for Genomic Medicine

  The goal of this study was to identify genetic risk factors for drug-induced prolongation of the QT interval (diLQT) and the ventricular arrhythmia torsades de pointes (TdP). We conducted a genome-wide association study (GWAS) focusing on subjects with a history of long QT and/or TdP after taking medication. Controls for this study were individuals with a history of cardiac arrhythmias who had begun treatment with potentially QT-prolonging antiarrhythmics. An additional control group of normal volunteers were given ibutilide, a drug with documented proarrhythmic properties. All study participants were recruited and treated/evaluated at Vanderbilt University Medical Center. This study was conducted by the Pharmacogenomics of Arrhythmia Therapy subgroup of the Pharmacogenetics Research Network, a nationwide collaboration of scientists studying the genetic contributions to drug response variability. Genotyping was performed by the RIKEN research institute in Japan using the Illumina 610 Quad Beadchip platform.

  Study phs000331

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): NIH Digital Health Solutions for COVID-19: Team SAE

  The goal of this project is to develop a smartphone-based platform to monitor and support individuals with COVID-19 symptoms (who may need testing) and those who have already tested positive. The app will integrate a Bluetooth-enabled thermometer and pulse oximeter into an approach uniquely designed for low-resource settings and underserved populations. This project will focus on the American Indian/Alaskan Native (AI/AN) underserved population and will determine the feasibility of the digital health solution to collect symptom survey data and vital data including temperature, pulse, and oxygen saturation level. The complete study will include 300 participants 100% medically underserved with at least 51% from the AI/AN community. A combination of hard and soft data will be collected consisting of vital data, medical history and questionnaire data, and participant COVID-19 viral and antibody testing results collected during the study.DOI: https://rapids.ll.mit.edu/10.57895/wv88-by98

  Study phs002534

• Deterministic Evolution and Stringent Selection During Pre-Neoplasia

  The earliest events during human tumor initiation are poorly characterized but may hold clues as to how to detect and prevent malignancy. Here we model this occult process by engineering TP53 deficiency in primary human gastric organoids and performing experimental evolution in multiple clonally derived cultures over two years, thereby defining causal relationships between this common initiating genetic lesion and resulting phenotypes. TP53 loss induced progressive aneuploidy, including copy number alterations and complex structural variants that are common in established gastric cancers, and which accrued along a defined temporal order. Longitudinal single cell sequencing of TP53 deficient gastric organoids similarly indicates progression towards malignant transcriptional programs. Moreover, lineage tracing with expressed cellular barcodes revealed highly reproducible dynamics whereby initially rare subclones with shared transcriptional programs repeatedly attain clonal dominance. This powerful platform for experimental evolution reveals stringent selection and convergence at the genotypic and phenotypic levels in pre-malignant epithelial organoids, illuminating evolutionary constraints and barriers to malignant transformation.

  Study phs003249

• California Teachers Study (CTS): Whole Genome Sequences From Under-Represented Populations

  The California Teachers Study (CTS) is a prospective observational cohort of N=133,477 adult women who have been followed since 1995. Participants completed up to six surveys and have been linked with cancer, hospitalization, and mortality data. In 2013-2016, over 14,000 CTS participants donated blood samples for future research. For this project, DNA was extracted in 2023 from 1694 buffy coats and 56 blood clots from N=1750 CTS participants whose self-reported race/ethnicity was Asian (398), Asian or Pacific Islander (18), Black or African American (189), Native American (128), Native Hawaiian or Other Pacific Islander (66), White Hispanic (719), or more than one race (232). Whole genome sequencing (WGS) was performed at CIDR in 2023-2024. WGS data and accompanying phenotype data are available through dbGaP. In addition, all CTS data are available to the research community via the CTS Researcher Platform (www.calteachersstudy.org), a secure cloud-based environment that includes data, software, documentation, and collaboration workspaces.

  Study phs002918

• Comprehensive assay for the molecular profiling of cancer by target enrichment from formalin-fixed paraffin-embedded specimens

  Tumor molecular profiling is becoming a standard of care for patients with cancer, but the optimal platform for cancer sequencing remains undetermined. We established a comprehensive assay, the Todai OncoPanel (TOP), which consists of DNA and RNA hybridization capture-based next-generation sequencing panels. A novel method for target enrichment, named the junction capture method, was developed for the RNA panel to accurately and cost-effectively detect 365 fusion genes as well as aberrantly spliced transcripts. The TOP RNA panel can also measure the expression profiles of an additional 109 genes. The TOP DNA panel was developed to detect single nucleotide variants and insertions/deletions for 464 genes, to calculate tumor mutation burden and microsatellite instability status, and to infer chromosomal copy number. Clinically relevant somatic mutations were identified in 32.2% (59/183) of patients by prospective TOP testing, signifying the clinical utility of TOP for providing personalized medicine to cancer patients.

  Study JGAS000164

• Quick Guide for data submission

  Quick Guide This is a quick guide to submit data to the EGA. Please select data type to display the right detailed instructions. Sequence data Array-based data Get your submission account You first need to create your EGA user. Then, once your account has been verified by the Help Desk team, request your submission account and provide details of the data type and platform(s) in your submission. Register Study/DAC Use Submitter Portal to register your study, samples, Data Access Committee (DAC) and Policy. Upload data Encrypt your data files using the and upload it to your inbox using SFTP. Register experiments and runs Associate each data file to a registered sample and study by Linking files to samples. Details of the experimental procedure you followed must be provided. Finalise your submission Group your runs/analysis into datasets and link them to your new or existing DAC and policy using DAC Portal. Data request are done at a dataset level, thus files within a datasets must share release conditions. Release and admin When finalising the submission, set a released date to instruct our Helpdesk to release your study. All registered studies are automatically placed on hold until the named submission or DAC contact instructs our Helpdesk for the study to be released. Get your submission account Fill the submission form and provide details of the data type and platform(s) in your submission. Register Study/DAC Use EGA Programmatic submission to register your study, samples, Data Access Committee (DAC) and Policy. Upload data Encrypt your data files using the EgaCryptor and upload it using default FTP clients or Aspera. Complete the Array-Format (AF) spreadsheet Download the AF spreadsheet and complete all four sections. Return the spreadsheet to the EGA helpdesk. Release and admin Instruct our Helpdesk to release your study. All registered studies are automatically placed on hold until the named submission or DAC contact instructs our Helpdesk for the study to be released.

  Documentation submission/quickguide

• Establishment and characterization of circulating tumor cells-derived organoids from metastatic breast cancer patients.

  Over the last decade, molecular stratification and associated therapies have greatly improved the treatment options and prognosis of patients diagnosed with breast cancer. However, metastatic disease remains incurable. Breast cancer cells mainly spread to the lung, liver, bone and brain and circulating tumor cells (CTCs) that migrate in the lymphatics or blood have been implicated as the cellular source of metastasis. Detailed molecular and functional characterization of patient CTCs remains poor due to their low number in patient’s bloodstream. In addition, CTCs are difficult to culture and expand ex vivo. Here we have established a novel method for culturing and unlimitedly expanding breast cancer patient-derived CTCs in CTC-derived organoids (CDOs). Our platform can serve as a foundation for serial longitudinal isolation and expansion of breast cancer cells from peripheral blood. This may enable the identification and functional validation of therapy resistance mechanisms during disease progression, which can be used for new approaches in precision medicine.

  Study EGAS00001007582

• Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells

  Most human breast cancers have already diversified genomically when they first become clinically evident, by which time extensive heterogeneous histopathologies, transcriptomes and growth patterns are also apparent. Accordingly, important initial events and the cellular context in which they occur have been difficult to characterize. Using DNA barcoding, we now demonstrate the high efficiency with which both purified basal and luminal cells isolated directly from normal adult human mammary tissue can be rapidly transformed by a single oncogene (KRASG12D) resulting in the production within 8 weeks in vivo of serially transplantable, polyclonal, invasive ductal carcinomas that are phenotypically heterogeneous and transcriptionally distinct from the initial cells transduced. Barcoding also revealed a consistent dramatic change in the clonal content of passaged tumours. This system thus provides a powerful new platform for examining early events in the genesis, evolution and treatment response of malignant human mammary cells generated using defined mutations.

  Study EGAS00001001310

• Longitudinal Single-Cell Profiling Reveals Molecular Heterogeneity and Tumor-Immune Evolution in Refractory Mantle Cell Lymphoma

  The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that the molecular targeting of BIRC5/survivin, locates at 17q and upregulates in resistant MCL tumor cells, results in marked tumor inhibition in preclinical models. In addition, we discovere notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveales diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.

  Study EGAS00001005019

• COVID19 Host Genetic Initiative

  The COVID-19 host genetics initiative is a bottom-up collaborative effort that has three main goals: 1. Provide an environment to foster the sharing of resources to facilitate COVID-19 host genetics research (e.g. protocols, questionnaires). 2. Organize analytical activities across studies to identify genetic determinants of COVID-19 susceptibility and severity. 3. Provide a platform to share the results from such activities, as well as the individual-level data where possible, to benefit the broader scientific community. Here, we release the harmonized individual-level data for the subset of individuals who participated in COVID-19 HGI. Please refer to this data dictionary: https://docs.google.com/spreadsheets/d/1whu_MjShXxbdoAJMCYxZ5C-vWOcRivwfWglTcBRNZgQ/edit#gid=470747846 Please cite both Nakanishi, T el al. J Clin Invest 2021 (PMID: 34597274) and COVID-19 Host Genetics Initiative, Nature 2021 (PMID: 34237774) when you use these data for your publications.

  Study EGAS00001005304

• Using de novo assembly to identify structural variation of complex immune system gene regions

  Driven by the necessity to survive environmental pathogens, the human immune system has evolved exceptional diversity and plasticity. Several factors contribute to this including inheritable structural polymorphism of the underlying genes. To investigate this we generated data for a single healthy European individual (identified as HV31) using multiple long-read (PacBio Sequel II and Oxford Nanopore), short-read (Illumina HiSeq and MGI G400) and linked-read (10X Chromium and stLFR) sequencing platforms, and optical mapping using the Bionano Saphyr platform. DNA was extracted from monocytes or from peripheral blood mononuclear cells. We used these data to assemble a set of regions encoding components of the immune system and to investigate structural variation. The raw data and analysis results are deposited here for generate research use. A complete description of these data and results can be found in the accompanying article at https://doi.org/10.1101/2021.02.03.429586.

  Study EGAS00001005046

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

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

  Study EGAS00001005935

• Pediatric Patient-Derived-Xenograft development in MAPPYACTS – international pediatric cancer precision medicine trial in relapsed and refractory tumors

  Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient’s tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Paediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This new PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and new treatments development in advanced pediatric malignancies.

  Study EGAS00001007327

• T cell and Antibody Responses in Rituximab-Treated Lymphoma Patients After SARS-CoV-2 Vaccination

  This dataset contains T cell receptor (TCR) sequencing data from 51 RNA samples, each processed into three independent libraries (tot 153 FASTQ files). Sequencing was performed on an Illumina NextSeq 500 platform using the NextSeq 500/550 Mid Output Kit v2.5 (300 Cycles), generating paired-end FASTQ files with dual 10 bp barcodes and 5% PhiX as internal control. Libraries were quantified with the Qubit HS dsDNA kit and assessed for fragment size distribution using the Agilent Tapestation D1000 system before isochoric pooling to 4 nM and sequencing in two independent runs. The resulting dataset enables analysis of TCR β-chain CDR3 sequences for clonal expansion and diversity studies.

  Dataset EGAD50000001714

• Data access to Small RNA-Seq of MicroRNA's in Tear EV's of Ushers Syndrome patients

  Via this DAC you can get access to Small RNA-Seq dataset of MicroRNA's in Tear EV's of Ushers Syndrome patients. The study involved genetically confirmed USH1B patients and their healthy relatives, with additional fibroblast samples from Spanish collaborators, to ensure a robust comparison of small non-coding RNAs (sncRNAs). Tear and blood samples were collected using non-invasive methods, and extracellular vesicles (EVs) were isolated from both tears and hiPSC-derived retinal pigment epithelium (RPE) cells. RNA was extracted from these EVs and assessed for quality before preparing libraries using the TruSeq Small RNA Library Preparation Kit. Sequencing was performed on the Illumina NextSeq 2000 platform, generating data for comparative analysis of sncRNA profiles between patients and controls.

  Dac EGAC50000000711

• Transcriptomic profiling of T cells following ABHD11 inhibition

  This dataset contains paired-end RNA sequencing data from human T cells treated with ML226, a selective ABHD11 inhibitor, and matched vehicle controls. The experiment was designed to investigate the role of ABHD11 in sterol metabolism and its impact on T cell effector function and autoimmunity. Samples were collected across biological replicates following 24-hour treatment, and RNA was extracted for high-throughput sequencing. Sequencing was performed using an Illumina platform. The dataset supports analysis of differentially expressed genes, alternative transcript usage, and pathway-level effects of ABHD11 inhibition. This dataset is part of the study titled "ABHD11 inhibition drives sterol metabolism to modulate T cell effector function and alleviate autoimmunity".

  Dataset EGAD50000001845

• RoCK and ROI single-cell transcriptome of one acute lymphoblastic leukemia patient

  Whole-transcriptome single-cell RNA sequencing (scRNA-seq) was performed following the manufacturer’s protocol (BD Rhapsody, BD Biosciences). Targeted enrichment of BCR::ABL1 transcripts was conducted using the RoCK and ROI-seq approach, based on the barcoded bead technology of the BD Rhapsody platform. In the RoCK and ROI-seq workflow, the template-switch oligonucleotides (TSOs) attached to BD Rhapsody beads were modified with one or multiple capture sequences specific to transcripts of interest, enabling targeted transcript capture during reverse transcription. ROI primers that are added during library preparation to direct amplification and sequencing toward these defined regions of interest (ROIs). Resulting libraries were sequenced on an Illumina sequencer.

  Dataset EGAD50000001976

• scCRISPRi/a-seq Control and IFN treated iPS derived human GPC/OPCs

  Datasets consists of 2 batches of human glial progenitors (iPS), cells were sequenced as controls and IFN treated. Using the 10Genomics platform from the samples 2 libraries were built forgene expression libraries (scRNA-seq) and captured guides sequencing library (gRNA) on a set of Multiple Sclerosis associated SNPs. Batch one includes KRAB and P300 perturbed cells in 2 rounds sequenced RNA libraries for Ctrl and IFN and 1 round of capture guides for Ctrl and IFN. Batch 2 includes 1 round of both RNA expresison library and captures guides for KRAB and P300 perturbations in Ctrl and IFN treated cells.

  Dataset EGAD50000002053

• Bulk RNAseq FASTQ files of three PDAC organoid lines treated with LGK974 or DMSO for 24h

  This dataset contains raw FASTQ files from bulk RNA sequencing of three patient-derived pancreatic ductal adenocarcinoma (PDAC) organoid lines (P28, P40, P47). Each organoid line was treated with either the WNT secretion inhibitor LGK974 or DMSO for 24 hours, with three biological replicates per treatment condition. RNA was extracted using the Qiagen QiaSymphony SP system, and libraries were prepared with the Illumina Truseq stranded polyA kit. Sequencing was performed on an Illumina NextSeq2000 platform using single-end 50bp reads. Quality control was conducted with FastQC, and reads were trimmed with TrimGalore as appropriate. Data are controlled-access and intended for transcriptomic analysis of WNT pathway perturbation in PDAC organoid models.

  Dataset EGAD50000002219

• RNA-seq of iPSC-derived oligodendrocytes of individuals with and without t(1;11) translocation

  This dataset contains high-throughput RNA-sequencing of 14 samples, each sample comprising oligodendrocytes derived from human induced pluripotent stem cells, from individuals with and without a balanced t(1;11) translocation which substantially increases risk of major mental illness. 5 samples derive from 2 control individuals, and 9 samples from 3 individuals carrying the translocation. Libraries were prepared from each total-RNA sample using the TruSeq Stranded Total RNA with Ribo-Zero kit. Libraries were then sequenced using the NextSeq 500/550 High-Output v2 (150 cycle) Kit on the NextSeq 550 platform. Raw paired-end sequencing data is stored in two FASTQ files per sample.

  Dataset EGAD00001006341

• European Prospective Investigation into Cancer and Nutrition BAMs

  516 DNA samples were collected from individuals upon enrollment into the European Prospective Investigation into Cancer and Nutrition study between 1993 and 1998 across 17 different centers. 126bp pair-end reads sequencing data from the Illumina platform were converted to fastq format, the 2bp molecular barcode information at each read of the pair was trimmed and was written in the reads name. The Thymine nucleotide required for ligation was removed from the sequences. Burroughs-Wheeler Aligner (BWA-mem) was used for alignment of the processed fastq files to the reference hg19 genome, following indel-re-alignment using GATK. An in-house algorithm was written to collapse read families that share the same molecular barcode sequence

  Dataset EGAD00001003583

• Whole genome sequencing of multiple myeloma patient samples.

  Tumor (CD138+ plasma cells) and non-tumor (peripheral blood white cells or stem cell harvest) DNA from patients with a plasma cell dyscrasias were sequenced. Whole genome sequencing using high molecular weight DNA was performed using the 10X Genomics Chromium platform on either a HiSeq4000 or NovaSeq (Illumina) using 100 to 150 bp paired-end reads. The dataset consists of 111 patients, and 223 samples in total (matched tumor and control per patient; one patient had 2 tumor samples sequenced). Diseases consisted of 2 MGUS patients, 8 SMM patients, 91 newly diagnosed myeloma patients, 1 previously treated patient, 4 relapsed MM patients, and 5 PCL patients. Paired RNA-seq data are available for 81 of the samples under study EGAS00001003411.

  Dataset EGAD00001004452

• Exome sequencing of a Novel Primary T Cell Immunodeficiency Kindred (2019-08-19)

  Primary T cell immunodeficiency disorders have a heterogeneous genetic basis. This study will focus on one case characterised by severe T cell lymphopenia in the index case. We aim to sequence the complete exomes of this individual, her three unaffected siblings and parents in an effort to identify the causative genetic mutation responsible for this disorder. We will perform exome capture using Agilent SureSelect system, followed by sequencing on the HiSeq platform. Our study has the potential to uncover genes important for T cell development and novel therapeutic strategies to treat T cell immunodeficiencies. . This dataset contains all the data available for this study on 2019-08-19.

  Dataset EGAD00001005263

• Target-capture sequencing of FFPE tumor samples from patients diagnosed with NKTL

  211 NKTL FFPE specimens were screened for somatic mutations using deep targeted capture sequencing. FFPE rolls or slides were extracted using QIAamp DNA FFPE Tissue kit (QIAGEN). The FFPE genomic DNA was treated with NEBNext FFPE DNA Repair Mix and assessed by Quant-it PicoGreen dsDNA Assay Kit (Invitrogen). The library was generated from 10-200 ng DNA with SureSelectXT Low Input Target Enrichment System for Illumina Paired-End Sequencing Library (Agilent Technologies) according to manufacturer’s instructions. RNA based probe was designed with SureDesign (Agilent Technologies) to target-capture 140 genes. Next, the captured libraries were pooled in equimolar concentration and sequenced on Illumina Novaseq 6000 platform with SP or S1 chip.

  Dataset EGAD00001005303

• WGBS Discovery Samples

  The dataset contains valuable genomic data from a discovery cohort consisting of 29 individuals. This cohort is comprised of 8 healthy individuals (control), 8 patients with ST-segment elevation myocardial infarction (STEMI), 7 patients with non-ST-segment elevation myocardial infarction (NSTEMI), and 6 patients with unstable angina (UA). The genomic data was obtained by isolating cell-free circulating DNA (ccfDNA) and subjecting it to bisulfite conversion using a low-input BS-seq (PBAT) protocol. Sequencing was done on the Novaseq 6000 platform.

  Dataset EGAD00001010935

• Longitudinal RNA-seq datasets from patients after abdominal surgery

  This dataset consists of RNA-seq data of 126 whole-blood samples derived from patients after abdominal surgery. Total-RNA collected preoperatively and at 3-time points postoperatively (2-6, 24 and 48hrs) were analysed using RNA-sequencing. RNA was collected in PAXGene (Qiagen) tubes and extracted using the PAXGene RNA extraction kit, with a DNase step to remove contaminating DNA. Globin and ribosomal RNA were removed via a Ribo-zero kit (Illumina) and library preparation was carried out using the TruSeq Stranded Total RNA Library Prep Kit (Illumina). Next generation sequencing was performed on the NovaSeq sequencing platform (Illumina) at the Wellcome Centre for Human Genetics (WCHG) in Oxford.

  Dataset EGAD00001011102

• Molecular Subtyping Reveals Immune Alterations Associated with Progression of Bronchial Premalignant Lesions

  Exposure to cigarette smoke creates a field of injury throughout the entire respiratory tract inducing genomic alterations that lead to an "at-risk" airway where lung cancers develop. Lung squamous cell carcinoma (SCC) arises in the epithelial layer of the bronchial airways and is often preceded by the development of premalignant lesions (PMLs). Effective tools to identify and treat premalignant lesions at highest risk of progression to invasive carcinoma are not available. Endobronchial biopsies and brushings were obtained from high-risk subjects undergoing lung cancer screening at approximately 1-year intervals by white light and auto-fluorescence bronchoscopy and computed tomography at the Roswell Park Cancer Institute in Buffalo, NY. Subjects were selected that had biopsies collected in repeat locations via serial bronchoscopies. mRNA sequencing was performed on a discovery cohort (DC) of samples comprising endobronchial biopsies and brushes collected between 2010 and 2012 (n=30 subjects, n=197 biopsies, and n=91 brushings). mRNA sequencing was subsequently performed on a validation cohort (VC) of samples comprising endobronchial biopsies and brushes collected between 2010 and 2015 (n=20 subjects, n=111 biopsies, and n=49 brushings). Data analysis identified four distinct molecular subtypes (Proliferative, Inflammatory, Secretory, and Normal) in the bronchial biopsies that correspond to a spectrum of biological and morphological alterations. The Proliferative subtype was enriched with dysplastic PMLs from current smokers that exhibit up-regulation of metabolic and cell cycle pathways and down-regulation of cilium-associated processes. Molecular subtype classification in the validation cohort biopsies replicated these significant clinical and biological associations. Airway brushes from normal fluorescing areas of the large airway classified as the Proliferative subtype specifically predict the presence of biopsies of this same subtype. Within the Proliferative subtype, genes associated with interferon signaling and antigen processing and presentation were observed to be down-regulated among dysplastic biopsies that persist or progress in the future. Innate and adaptive immune cells were computationally predicted to be depleted in these biopsies and this was confirmed via immunofluorescence staining of adjacent biopsies. These findings provide a proof of concept that molecular biomarkers of endobronchial biopsies can enhance histopathological grading and that immunoprevention strategies are an important future direction in intercepting the progression of PMLs to lung cancer.FASTQ files from the RNA sequencing of these biopsies and brushings will be available via dbGaP.

  Study phs003185

• 3q-capture DNA sequencing of primary AMLs with 3q26 rearrangements

  This dataset contains DNA sequencing of the chromosome 3q region in 28 primary AML cases with 3q26 rearrangements (3q26-rearranged AML). Genomic DNA was fragmented using the Covaris shearing device (Covaris), and sample libraries were assembled following the TruSeq DNA Sample Preparation Guide (Illumina). After ligation of adapters and an amplification step, target sequences of chromosomal regions 3q21.1-q26.2 were captured using custom in-solution oligonucleotide baits (Nimblegen SeqCap EZ Choice XL). The design of target sequences was based on the human genome assembly hg19: chr3q21.1:126036241-130672290 - chr3q26.2:157712147-175694147. Amplified captured sample libraries were paired-end sequenced (2x100 bp) on the HiSeq 2500 platform (Illumina) and aligned against the hg19 reference genome using the Burrows-Wheeler Aligner (BWA).

  Dataset EGAD00001006820

• Brazilian Thyroid WES

  Medullary thyroid cancer (MTC) is a rare malignant tumor that arises from parafollicular cells. Approximately 8% of thyroid cancer cases are MTC, and about 25% of these have a hereditary component. Incorporating molecular parameters into tumor classification is important. Besides, the presence of pathogenic germline variants can impact directly on cancer prevention. Thus, the aim of this study was to perform whole exome sequencing (WES) on a consecutive series of hereditary RET wild-type MTC patients to identify genetic variants that may be involved in the carcinogenesis of this tumor. WES was performed on 28 patients negative for germline RET pathogenic variants using the NovaSeq 6000 platform. Variant classification followed American College of Medical Genetics and Genomics guidelines.Our study represents a significant advancement in gene discovery for MTC genetics.

  Dataset EGAD50000000086

• WES analysis of tumor samples from ER+ breast cancer patients treated with CDK4/6 inhibitor

  We performed whole exome sequencing of paired fresh frozen tumor from 4 ER+ advanced breast cancer patients. Samples were obtained for each patient prior to combined CDK4/6 inhibitor and endocrine therapy and at disease progression (N=8). DNA was extracted using the Maxwell® RSC FFPE and Tissue DNA Kit (Promega). WES was performed at the Department of Molecular Medicine, Aarhus University Hospital on matched tumor DNA (derived from primary fresh frozen and FFPE tissue) and buffy coat DNA. Libraries of tumors and matching germline DNA were prepared using 50 ng DNA and captured by Twist Comprehensive Exome with custom spike-ins, sequenced on the Illumina NovaSeq 6000 platform to an average coverage of 413x (range: 148-515x). The dataset include the analysis data files (vcf files).

  Dataset EGAD50000000622

• Project for Development of Innovative Research on Cancer Therapeutics;Shuttle system between petient-derived xenograft and ex vivo culture for innovative platform of evaluating drug sensitivity.

  We developed CTOS (cancer tissue-originated spheroid) panel covering diversity among patients for colorectal cancer, lung cancer and cervical small cell carcinoma. We then carried out exome sequence analysis of tumor tissues, cell lines and CTOS derived from patients to validate qualitative changes in preparation, culture, cell line, transplantation and passage of CTOS pathologically, biochemically, molecular biologically.

  Study JGAS000089

• Bulk RNAseq FASTQ files of WNT7B reporter PDAC organoids (P28 and P40) sorted by mNeonGreen high and low

  This dataset contains raw FASTQ files from bulk RNA sequencing of two patient-derived PDAC organoid lines (P28 and P40) carrying a WNT7B reporter knock-in. Organoids were sorted into mNeonGreen high (WNT-high) and low (WNT-low) populations, with three biological replicates per sorted population. RNA was extracted using the Qiagen QiaSymphony SP system, and libraries were prepared with the Illumina Truseq stranded polyA kit. Sequencing was performed on an Illumina NextSeq2000 platform using single-end 50bp reads. Quality control was conducted with FastQC, and reads were trimmed with TrimGalore as appropriate. Data are controlled-access and intended for transcriptomic analysis of WNT7B expression-dependent transcriptional programs in PDAC organoids.

  Dataset EGAD50000002218

• Single cell RNAseq FASTQ files of three PDAC organoid lines (P28, P40, P47) using SORT-seq

  This dataset contains raw FASTQ files from single cell RNA sequencing of three patient-derived pancreatic ductal adenocarcinoma (PDAC) organoid lines (P28, P40, P47) cultured under standard conditions. For each line, single cells were FACS sorted into 384-well capture plates, with each well containing a 50nl droplet of barcoded primers. Plates were processed following an adapted SORT-seq protocol, and cDNA libraries were generated using CEL-Seq2 with TruSeq small RNA primers (Illumina). Sequencing was performed on an Illumina NextSeq500 platform using paired-end reads (read 1: 26 cycles, index read: 6 cycles, read 2: 60 cycles). Data are controlled-access and intended for single cell transcriptomic analysis of PDAC organoid heterogeneity and WNT pathway activity.

  Dataset EGAD50000002220

• Pediatric Papillary Thyroid Carcinoma RNA-Seq

  38 PPTCs were sequenced using RNASeq to identify oncogenic variants in driver-unknown tumors and to explore gene expression patterns. RNA libraries were quantified by qPCR using the Kapa Library Quantification Illumina/ABI Prism Kit protocol (KAPA Biosystems). Libraries were pooled in equimolar quantities and paired-end sequenced on 2 lanes of a High Throughput Run Mode flowcell with the V4 sequencing chemistry on an Illumina HiSeq 2500 platform following Illumina’s recommended protocol to generate paired-end reads of 126-bases in length.

  Dataset EGAD00001007499

• 5 scRNA-seq with TCR Enrichment of Tumour-Involved Lymph Nodes, Malignant Seromas and Patient-Derived Xenografts from 18 T-Cell Lymphoma Patients

  This raw data contains 5' scRNA-seq with TCR enrichment data from 18 individual patients analysing cells taken from tumour-involved lymph nodes (LN), malignant seromas and patient-derived xenografts (PDX) including systemic/nodal ALK+ ALCL (n=3 PDX), BIA-ALCL (n=2 seromas), PTCL-NOS (n=5 nodal tumours), nodal T follicular helper lymphoma - angioimmunoblastic type (nTFHL-AI) (n=1), nTFHL, not otherwise specified (nTFHL, NOS, n=1), TLBL (n=5) and 1 case of Sezary Syndrome (SS, cutaneous tumour). Droplet-based 5’ scRNA-seq with TCR enrichment (10x Chromium platform) was performed for all live cells, or the viable CD45+CD3- and CD45+CD3+ fractions following cell sorting by flow cytometry.

  Dataset EGAD00001015703

• Targeted Validation Samples

  The dataset consists of targeted sequencing data obtained from an independent cohort of 11 patients to validate discriminative DMRs (differentially methylated regions) for Acute coronary syndrome (ACS) subtypes. The cohort includes 2 healthy subjects, 4 STEMI (ST-segment elevation myocardial infarction), 3 NSTEMI (non-ST-segment elevation myocardial infarction), and 2 UA (unstable angina) patients. The sequencing panel targeted 18,831 CpGs for analysis, reaching at least 5 reads coverage for 75% of the targeted CpGs in each sample. The sequencing was performed using the NEBNext Enzymatic Methyl-seq Module and the Nonacus Cell3TMTarget: Library Preparation kit, followed by probe hybridization, capture enrichment, and sequencing on the Novaseq 6000 platform, generating 400 million reads. The dataset is in raw fastq format.

  Dataset EGAD00001010934

• A Genome-Wide Association Study in Patients Experiencing Breast Events While Receiving Adjuvant Aromatase Inhibitors for Early Breast Cancer on NCIC CTG Trial MA.27

  Source of patients:The source of the patients for this genome-wide case-control study was MA.27, which was conducted as a multi-cooperative group effort under the auspices of the NCI Breast Cancer Intergroup of North America. The NCIC Clinical Trials Group (CTG) serves as the coordinating group, with participation by the NCI-sponsored North Central Cancer Treatment Group, Eastern Cooperative Oncology Group (ECOG), Southwest Oncology Group, and Cancer and Leukemia Group B (CALGB). MA.27 involved postmenopausal women with histologically confirmed and completely resected invasive breast cancer with surgical margins clear of invasive carcinoma in the following TMN categories (AJCC Version 6): pT1, pT2, pT3; pNx, pN0, pN1, pN2, pN3 (only when the sole basis is presence of 10 or more involved axillary nodes); MO. The primary tumor must have been estrogen receptor (ER) and/or progesterone receptor positive. Patients were stratified by lymph node status at diagnosis, prior adjuvant chemotherapy, and trastuzumab use and were randomized to 5 years of adjuvant therapy with anastrozole or exemestane. The trial was activated on May 26, 2003, and reached its accrual objectives on July 31, 2008, after the randomization of 6827 North American patients, with the majority (79%) providing DNA and consent for genetic testing. Non-North American patients were also entered by the International Breast Cancer Study Group but they did not contribute DNA. From 2003 to December 21, 2004, patients also underwent a second randomization to celecoxib 400 mg twice daily or placebo but, after the entry of 1,622 patients, this treatment was discontinued because of reports of increased cardiovascular risk associated with celecoxib. The final results of this study have been published, see Goss et al., 2013 (23358971). The patients in this analysis came from three cohorts: Cohort 1 consisted of 870 patients genotyped on the Illumina Human610-Quad BeadChip studied in a GWAS with the phenotype of musculoskeletal adverse event, see Ingle et al., 2010 (20876420), Cohort 2 consisted of 882 patients genotyped on the Illumina OmniExpress platform studied in a GWAS with the phenotype of fragility fractures, see Liu et al., 2014 (25148458), and the remaining 2913 patients were genotyped with the Illumina OmniExpressExome platform.

  Study phs001043

• Acute Respiratory Distress Network (ARDSNet) Studies 10 and 12 Statins for Acutely Injured Lungs from Sepsis (SAILS) (ARDSNet-SAILS-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Biospecimens Access to Biospecimens is through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC). Biospecimens from ARDSNet-SAILS include Plasma, DNA, and Urine. Please note that use of biospecimens in genetic research is subject to a tiered consent. Objectives The SAILS trial was intended to assess the efficacy and safety of oral rosuvastatin in participants with sepsis-induced Acute Lung Injury (ALI) and test the hypothesis that rosuvastatin therapy would improve the clinical outcomes of critically ill participants with sepsis-associated acute respiratory distress syndrome (ARDS). Background In ARDS, inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in participants with sepsis. Participants There were 745 participants. Design Participants were randomly assigned in permuted blocks to receive either enteral rosuvastatin or placebo. A 40 mg loading dose of the study drug was administered within four hours after randomization. Subsequently, maintenance doses of 20 mg were administered daily until the third day after discharge from the intensive care unit, study day 28, hospital discharge, or death, whichever came first. The primary outcome measure was mortality before hospital discharge home or until study day 60 if the participant was still in a health care facility. Secondary outcome measures included the number of ventilator-free days to day 28, organ-failure-free days to day 14, and ICU-free days to day 28. Conclusions The study was stopped because of futility after 745 of an estimated 1000 participants had been enrolled. There was no significant difference between study groups in 60 day in-hospital mortality or in mean ventilator-free days. The rosuvastatin group had fewer days free of hepatic or renal failure. Thus, rosuvastatin therapy did not improve clinical outcomes in participants with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction.

  Study phs003736

• Circulating Tumor Cell Heterogeneity in Neuroendocrine Prostate Cancer by Single Cell Copy Number Analysis

  Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that may arise de novo or develop from pre-existing prostate adenocarcinoma as a mechanism of treatment resistance. Combined loss of tumor suppressors RB1, TP53, PTEN are frequent in NEPC but also present in a subset of prostate adenocarcinomas. Most clinical and preclinical studies support a trans-differentiation process, whereby NEPC arises clonally from a prostate adenocarcinoma precursor during the course of treatment resistance. Here we highlight a case of NEPC with significant intra-patient heterogeneity observed across metastases. We further demonstrate how single-cell genomic analysis of circulating tumor cells combined with phenotypic evaluation of cellular diversity can be considered as a window into tumor heterogeneity in patients with advanced prostate cancer. We performed whole genome sequencing of circulating tumor cells (CTCs) from patients with castration resistant adenocarcinoma (n=4) and neuroendocrine prostate cancer (n=8). CTCs were collected via Epic Sciences platform and single CTC genomic data (n=215) generated via Illumina NextSeq500. 

  Study phs002462

• Epigenetic Landscape of Human Parathyroids

  The goal of this study is to produce a comprehensive map of the chromatin landscape of human parathyroids. Data from 20 subjects with parathyroid adenoma causing primary hyperparathyroidism were used. For the sequencing platform, Illumina HiSeq 2000 with V3 high-output kits were used. For the data processing pipeline, reads were aligned to hg19 using Bowtie or BWA. For RNA-seq data, transcript levels were estimated per gene to RPKM using Cufflink. For ChIP-seq and ATAC-seq data, enrichment peaks were estimated compared to inputs or background using MACS2 after merging reads from replicates. For DNase-seq, significant peaks compared to background distribution were computed using Hotspot. For Hi-C data, significant interactions were detected using Juicer HiCCUPS and 5 kb resolution for the merged data from replicates. Chromatin states for parathyroids were computed using ChromHMM based on ChIP-seq profiles in parathyroids of H3K4me3, H3K4me1, H3K27ac, H3K36me3, H3K27me3 and H3K9me3 and the emission matrix from 18 states pre-trained in the Roadmap Epigenomics. Gene expression, binding positions of transcription factor, open chromatin regions, 3D-chromatin interaction, and chromatin states are submitted.

  Study phs003302

• Comprehensive Genomic Data Deposition for Pancreatic Cancer Precision Medicine Studies: Clinical Trials NCT02451982 and NCT02648282

  This submission includes specimens from 89 pancreatic cancer patients at Johns Hopkins Hospital, comprising 41 surgically resectable and 48 locally advanced pancreatic cancer (LAPC) cases. These samples originate from two clinical studies, NCT02451982 and NCT02648282, following the Johns Hopkins Medical Institution Institutional Review Board-approved registry protocol at the Pancreatic Cancer Precision Medicine Center of Excellence Program. Written consent for specimen use, obtained from participants in the original studies, covers additional research, including this one. Biopsy specimens collected through endoscopic ultrasound-guided fine needle core biopsies or surgically resected tumors are included. NCT02451982 is a platform trial evaluating immunotherapy combinations for surgically resectable pancreatic ductal adenocarcinoma in the neo-adjuvant and adjuvant settings. It investigates the GVAX pancreatic cancer vaccine with immune-boosting cyclophosphamide, exploring immune cell trafficking and the impact of PD-1 blocking. NCT02648282 focuses on the efficacy and safety of combining cyclophosphamide, pembrolizumab, GVAX, and stereotactic body radiotherapy (SBRT) in locally advanced pancreatic cancer, with an emphasis on anti-tumor activity. Both studies provide valuable insights into innovative pancreatic cancer treatment approaches.

  Study phs003600

• Fetal Genomics Consortium (FGC)

  Many of the congenital anomalies and associated genomic variants identified during prenatal care are rare, requiring aggregation and harmonization to assure their appropriate clinical interpretation and to support the expanding utility of genomics in perinatal medicine. The primary step in accomplishing this is the creation of interoperability allowing collection, collaborative storage, dissemination and use of harmonized and vetted genomic and phenotypic data. The overall goal of this project is to generate a prenatal repository for both clinical care and research ensuring data are Findable; Accessible; Interoperable; and Reusable. The specific goals are: (1) collect and organize data contributions from multiple sites using the cloud-based Terra platform; (2) establish a governance structure for data contributions across sites; (3) develop and implement a pipeline for phenotype driven analysis and implementation of fetal specific Phenopackets on Terra; (4) generate a searchable callset of genomic variants and phenotype features on Terra; and (5) explore methods for facilitating broad access and sharing of longitudinal phenotype and genomic data facilitating genomic analysis in the prenatal space.

  Study phs003193

• Genomic Analysis of Relapsed/Refractory DLBCL

  Molecular phenotyping techniques have established a landscape of genomic variants in diagnostic Diffuse Large B Cell Lymphoma (DLBCL), however these have not yet been applied in large scale studies of relapsed/refractory DLBCL resulting in incomplete characterization of mechanisms driving tumor progression and treatment resistance. Here, we performed an integrated multiomic analysis on relapsed/refractory DLBCL samples. Tumors from 87 relapsed/refractory DLBCL patients were included in this study and were available for data deposition [Tumor whole exome sequencing (WES): n=75, Germline WES: n=73, RNA sequencing (RNA-Seq): n=72]. Tumor DNA was extracted from formalin-fixed, paraffin embedded (FFPE) tissue sections, germline DNA was extracted from blood, and WES of all samples was performed using the Agilent SureSelect XT All Exon v6 kit and sequencing was carried out on an Illumina NovaSeq, 100 x 2 paired end reads. Tumor RNA was extracted from FFPE tissue sections and RNA-Seq was performed using the Illumina TruSeq RNA Exome Kit (Illumina) for library preparation, sequencing platform HiSeq 4000, 100 x 2 paired end reads.

  Study phs003868

• Human liver cholangiocyte organoids capture the heterogeneity of in vivo human liver ductal epithelium

  Human liver ductal epithelium is morphologically, functionally and transcriptionally heterogeneous. However, understanding the dynamics within human biliary/ductal epithelium has been hampered by the absence of an in vitro system that fully mimics its complex cellular heterogeneity. Here, we found that the human liver cholangiocyte (ductal-cell) organoids we previously published (Huch et al., 2015) are fairly homogenous and do not retain the cellular heterogeneity of the in vivo human biliary/ductal epithelium. Inspired by the knowledge of the in vivo niche, we refined our previous organoid culture medium to fully capture the cellular heterogeneity of the human ductal epithelium. We employed this refined system to analyse the interactions and relationships between the different human biliary epithelial cell states and discovered that acquiring a bipotent ductal cell state is necessary for differentiating the human ductal epithelium into functional hepatocyte-like cells. Our improved cholangiocyte organoid model represents a new platform to investigate cell plasticity and duct-to-hepatocyte differentiation in human liver.

  Study EGAS50000001000

• Hyperdiploidy impairs fetal hematopoietic progenitor cell fitness and differentiation enabling persistence of rare preleukemic aneuploid clones

  Cells previously cryopreserved in FBS-10%DMSO were thawed and resuspended in 1mL of cold lysis buffer (10 mM Tris-HCl pH 7.4, 154 mM NaCl, 0.2% BSA, 0.1% NP-40, 1 mM CaCl₂, 0.5 mM MgCl₂ in ultra-pure water) to lyse the cell membrane and release intact nuclei. The nuclei were stained with propidium iodide (10 µg/mL) and Hoechst 33258 (10µg/mL) to facilitate sorting based on cell cycle state and viability. Single nuclei from 48 cells per sample were isolated into 96-well plates containing 5µL of freeze buffer (1X PBS, 7.5% DMSO, and 40% ProFreeze freezing medium (Lonza)) using a MoFlo Astrios cell sorter (Beckman Coulter) at the Flow Cytometry Unit of the University Medical Center Groningen (UMCG), Netherlands. The plates were centrifuged at 500 g and stored at -80°C until library preparation. Single-nuclei libraries were prepared using a Bravo Automated Liquid Handling Platform (Agilent Technologies). Nuclei were lysed, and DNA was labelled with unique 10 bp dual barcodes and amplified as previously described. Sequencing was performed on an Illumina NextSeq 2000 platform with 77bp single end reads. The generated data were subsequently demultiplexed using sample-specific barcodes and converted to FASTQ files with bcl2fastq. Sequencing reads were aligned to the GRCh38/hg38 human reference genome using Bowtie2 (v2.2.4), and duplicate reads were marked with BamUtil (v1.0.3). Single-cell karyotypes were determined by performing copy number analysis using AneuFinder (v4.3.3) (https://github.com/ataudt/aneufinder). The analysis included GC-content correction and blacklisting of artifact regions identified from euploid controls. Copy number calling was conducted with the dnacopy and edivisive algorithms, employing a bin size of 1 Mb and a step size of 500 Kb. Libraries with an average of fewer than 10 reads per chromosome copy per bin or less than 95% concordance between the two algorithms were excluded from analysis. Whole-chromosome aneuploidies were identified when over 95% of bins exhibited deviation from the disomic state. Aneuploidy scores were calculated as weighted averages of absolute copy number deviations from the euploid state. 

  Dataset EGAD50000002314

• Passive and active DNA methylation and the interplay with genetic variation in gene regulation

  DNA methylation is an essential1 epigenetic mark whose role in gene regulation and its dependency on genomic sequence and environment are not yet fully understood2,3. In this study we provide novel insights into the mechanistic relationships between genetic variation, DNA methylation and transcriptome sequencing data in three different cell-types of the GenCord human population cohort4. We find that the association between DNA methylation and gene expression variation among individuals are likely due to different mechanisms from those establishing methylation-expression patterns during differentiation. Furthermore, cell-type differential DNA methylation may delineate a platform in which more local inter-individual changes may respond to or act in gene regulation. We show that unlike genetic regulatory variation, DNA methylation alone does not significantly drive allele specific expression.. Finally, inferred mechanistic relationships using genetic variation as well as correlations with TF abundance reveal both a passive and active role of DNA methylation to regulatory interactions influencing gene expression.

  Study EGAS00001000446

• Drug screening and whole genome sequencing of primary cells and cell lines from ovarian cancer patients to associate genomic aberrations with in vitro drug sensitivities

  Identifying drugs for cancers with poor prognosis like ovarian cancer (OC) is hindered by inappropriate cell models and the limitations of current viability assays. We developed an automated confocal microscopy-based live cell assay (DeathPro) that robustly de-convolves cell death and proliferation over time by employing a specific image processing strategy. Using DeathPro, we screened nine OC patient-derived cell lines and one normal cell line (HOSEpiC) with 22 drugs or combinations. Whole genome was performed to analyze if the cell lines harbor OC-typical genomic aberrations and to relate genomic features to drug sensitivities. Commonly observed alterations in OC patients like TP53 mutations and MYC or PI3KCA amplifications were absent in the normal cell line but frequently detected in the OC cell lines. Moreover, genome-derived homologous recombination deficiency (HRD) scores of the OC cell lines correlated with their responses to carboplatin, olaparib and DNA demethylation drugs. Overall, we propose an imaging-based platform to guide drug development and genome-drug sensitivity analysis.

  Study EGAS00001002239

• Genotype and exome data for an Australian Aboriginal population: a reference panel for health-based research

  Genetic analyses, including genome-wide association studies and whole exome sequencing (WES), provide powerful tools for the analysis of complex and rare genetic diseases. To date there are no reference data for Aboriginal Australians to underpin the translation of health-based genomic research. Here we provide a catalog of variants called after sequencing the exomes of 72 Aboriginal individuals to a depth of 20X coverage in 80% of the sequenced nucleotides. We determined 320,976 single nucleotide variants (SNVs) and 47,313 insertions/deletions using the Genome Analysis Toolkit. We had previously genotyped a subset of the Aboriginal individuals (70/72) using the Illumina Omni2.5 BeadChip platform and found 99% concordance at overlapping sites, which suggests high quality genotyping. Finally, we compared our SNVs to six publicly available variant databases, such as dbSNP and the Exome Sequencing Project, and 70,115 of our SNVs did not overlap any of the single nucleotide polymorphic sites in all the databases. Our data set provides a useful reference point for genomic studies on Aboriginal Australians.

  Study EGAS00001001585

• Genomic and functional fidelity of small cell lung cancer patient-derived xenografts

  Small cell lung cancer (SCLC) patient-derived xenografts (PDXs) can be generated from biopsies or circulating tumor cells (CTCs), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical-translational pipeline for tissue collection and an automated microfluidic platform for CTC-enrichment, we generated 17 biopsy-derived PDXs and 17 CTC-derived PDXs in a two-year timeframe, at efficiencies of 89% and 38%, respectively. Whole exome sequencing showed that somatic alterations are stably maintained between patient tumors and PDXs. Early-passage PDXs maintain the genomic and transcriptional profiles of the founder PDX. In vivo treatment with etoposide and cisplatin (EP) in 30 PDX models demonstrated greater sensitivity in PDXs from EP naïve patients, and resistance to EP corresponded to increased expression of a MYC gene signature. Finally, serial CTC-derived PDXs generated from an individual patient at multiple time points accurately recapitulated the evolving drug sensitivities of that patient’s disease. Collectively, this work highlights the translational potential of this strategy.

  Study EGAS00001002853