17510 results for "free coins in fc 26 Visit Buyfc26coins.com for latest FC 26 coins news..Y2KA"

in 56.16 milliseconds.

• Acquired Copy Number Alterations in Adult Acute Myeloid Leukemia Genomes

  We performed genome-wide copy number analysis with paired normal and tumor DNA obtained from 86 adult patients with de novo AML using the Affymetrix Genome-Wide Human SNP array 6.0 containing 1.85 million features. Acquired copy number alterations (CNA) were confirmed using an independent, higher resolution, custom array comparative genomic hybridization platform. A total of 201 somatic CNA were found in the 86 AML genomes (mean 2.34 CNA/genome), with FAB M6 and M7 AML genomes containing the most changes (10-29 CNA/genome). Twenty-four percent of AML patients with normal cytogenetics had CNA, while 40% of patients with an abnormal karyotype had additional CNA detected by SNP array, and several regions contained CNA in multiple AML genomes. The mRNA expression levels of 57 genes were significantly altered in 27 of 50 recurrent CNA regions <5 megabases in size. Array data are available online at http://www.ncbi.nlm.nih.gov/geo/ as GEO accession #GSE10358. A total of 8 uniparental disomy (UPD) segments were identified in the 86 genomes and 6/8 UPD regions occurred in samples with a normal karyotype. Collectively, 40% of AML genomes contained alterations not found with cytogenetics, and 96% of these regions contained known or novel AML associated genes. 43/86 AML genomes had no CNA or UPD at this level of resolution. The number of CNA per genome was not associated with overall survival, independent of cytogenetic classification. In this study of 86 adult AML genomes, subcytogenetic CNAs or UPD did not add prognostic information to standard cytogenetics. However, arrays identified many somatically mutated oncogenes and tumor suppressor genes, and also genes not previously implicated in AML that may be relevant for pathogenesis. AML CNA segments from 86 adult AML patients are available through dbVar at ftp://ftp.ncbi.nlm.nih.gov/pub/dbVar/data/Homo_sapiens/nstd11_Walter_et_al_2009.

  Study phs000201

• Exome Sequencing to Define the Landscape of Plasma Cells in Systemic Light chain Amyloidosis

  Systemic light chain amyloidosis (AL) is characterized by the deposition of immunoglobulin light chains as amyloid fibrils in different organs, where they form toxic protein aggregates. The underlying disease is a plasma cell disorder, but limited whole exome data are available. We report the findings of an exome sequencing study in AL to define a plasma cell signature and compare this to monoclonal gammopathy of undefined significance (MGUS) and myeloma (MM). Twenty-four samples from unselected newly diagnosed untreated AL patients were analysed. CD138+ cells were isolated from bone marrow cells using MACSorting (Miltenyi Biotech, Bisley, UK). Cells were lysed in RLT+ buffer and DNA/RNA extracted using the AllPrep kit (Qiagen, Manchester, UK). Peripheral blood was isolated from patients, white blood cells purified by Ficoll-Pacque and DNA extracted using the QIAamp DNA mini kit (Qiagen). There were a median of 47 acquired nonsynonymous variants (range 4-253) per patient. Thirty percent of patients yielded a mutation in a myeloma driver gene. These mutations were either clonal or sub-clonal. There was evidence of MAPK activation with NRAS mutations, NF-κB activation and DNA repair pathway alterations. Exome data were used to determine the cytogenetic groups of AL samples and identified hyperdiploidy in 33% of cases and t(11;14) in 33% of cases. All translocations were generated via class switch recombination and breakpoints on chromosome 11 fell into the expected regions. A novel translocation, unlikely to be driving disease progression was identified involving RCC1. Finally, further analysis of the APCS gene encoding for the SAP protein did not show any biased genotype in the AL population in comparison to the general population. We conclude that exome sequencing identifies a genetic make-up of AL that is similar to other plasma cell disorders such as MM and MGUS. This not only includes copy number abnormalities and translocations but also nonsynonymous mutations.

  Study EGAS00001001418

• Single Cell Dissection of the Tumour Microenvironment Reveals Dynamic Interplay Shaping the Tumour Immunity Continuum in Ovarian Cancer

  Diverse tumour immune phenotypes with distinct T cell infiltration patterns result in different responses to cancer immunotherapies. However, the key determinants and biology underpinning these phenotypes remain elusive. Here, we provide a high-resolution dissection of the tumour microenvironment representative of different tumour immune phenotypes. By performing single-cell RNA sequencing (scRNAseq) of the tumour, immune, and stromal compartments from 15 ovarian cancer patients, we characterized the diverse cellular and functional phenotypes, as well as dynamic interplay within and between these components. Infiltrated and excluded tumours markedly differed from desert tumours in several tumour cell intrinsic features, including high interferon response, antigen presentation and oxidative phosphorylation. Moreover, these tumours were characterized by tumour associated macrophage (TAM)-like myeloid subsets, while desert tumours were enriched in myeloid derived suppressive cell (MDSC)-like myeloid subsets. Infiltrated and excluded tumours differed in their T cell composition and fibroblast subsets. While dysfunctional CD8+ GZMB T cells and IL1-activated fibroblasts (IL1 CAFs) were associated with infiltrated tumours, pre-dysfunctional CD8+ GZMK T cells and TGFB-activated fibroblasts (TGFB CAFs) were enriched in excluded tumours. These findings validated in bulk transcriptomic profiles of 1071 ovarian tumours and using in situ hybridization. Furthermore, our study revealed chemokine receptor-ligand interactions within and across compartments as potential mechanisms mediating immune cell infiltration, exemplified by the tumour cell-T cell crosstalk via a CXC16-CXCR6 axis, stromal-immune cell crosstalk via CXCL12/14-CXCR4 signalling, and TAM-like macrophage-T cell crosstalk through CXCR3-CXCL9/10/11 signalling. Our in-depth characterization of the tumour environment and intercellular interactions provides novel insights into potential molecular mechanisms that shape the distinct biology of tumour immune phenotypes. Our findings may inform novel therapeutic strategies for potentially shifting tumours along the immunity continuum to improve clinical benefit from cancer immunotherapies.

  Study EGAS00001004935

• CIP: Differential Response to Hydroxyurea and Incidence of Stroke in Sickle Cell Disease

  Sickle cell disease (SCD) is a severe debilitating hematological disorder associated with a high degree of morbidity and mortality. There are approximately 200,000 babies born with sickle cell disease each year, with the disease predominately affecting individuals in Africa. The overall global burden of the disease is tremendous, with more than 100,000 patients currently in the US and further millions worldwide. The governing bodies of the World Health Organization have recently adopted a resolution to strengthen the response to sickle disease in all affected countries and there is a definite need for high quality sickle cell disease research that has the potential to improve the treatment and prognosis of patients with this devastating disease. The clinical manifestations of SCD arise from a complex pathophysiology that includes hemolysis, acute vaso-occlusion, endothelial dysfunction, inflammation, and chronic organ damage. While the individual clinical course of this disease is highly variable, many of the associated complications demonstrate some degree of heritability. Intensive research into identifying genetic modifiers that can affect the pathophysiology of SCD has been limited to date and there is an urgent need to improve of our knowledge the molecular mechanisms underlying the clinical complications of SCD. The Sickle cell CIP project is investigating complication of stroke and pharmacogenomics of hydroxyurea response in patients with sickle cell anemia. The major benefit of hydroxyurea comes from its ability to induce fetal hemoglobin (HbF) and higher HbF levels are associated with reduced morbidity and mortality in SCA patients. We will perform whole exome and whole genome sequencing of SCA patients in order to identify genome variants associated with incidences of stroke and HbF response to hydroxyurea.

  Study phs000691

• Leukemia Relapse via Genetic Immune Escape after Allogeneic Hematopoietic Cell Transplantation

  Graft-versus-leukemia (GvL) reactions are responsible for the effectiveness of allogeneic hematopoietic cell transplantation as a treatment modality for myeloid neoplasia, whereby donor T- effector cells recognize leukemia neoantigens. However, a substantial fraction of patients experience relapses because of the failure of the immunological responses to control leukemic outgrowth. Here we demonstrate, through a broad immunogenetic study, that germline and somatic reduction of human leucocyte antigen (HLA) heterogeneity enhances the risk of leukemic recurrence. We show that preexistent germline-encoded low evolutionary divergence of class II HLA genotypes constitutes an independent factor associated with disease relapse and that acquisition of clonal somatic defects in HLA alleles may lead to escape from GvL control. Both class I and II HLA genes are targeted by somatic mutations as clonal selection factors potentially impairing cellular immune responses and responses to immunomodulatory strategies. These findings define new molecular modes of post-transplant leukemia escape contributing to relapse.The present dataset provides HLA peripheral blood and bone marrow samples supporting the genotyping studies performed for this research. This sample set originates from patients with acute myeloid leukemia or myelodysplastic syndromes receiving allogeneic hematopoietic cell transplantation and relapsing after transplant.

  Study phs003235

• Profiling_the_Microbiome_of_Early_Life_Gut_Samples

  The human gut microbiome (GM), defined as the microorganisms that reside in the human gastrointestinal tract, has been identified as critical for normal intestinal development and physiology. However, to-date, the majority of studies characterizing the gut microbiome has relied on stool samples, thereby limiting insights into the regionality of the gut and how its microbiota differs along its length. As a result, this project seeks to profile the adjacent microbiota of various regions along the intestinal tract from pediatric intestinal tissue and their associated mucosal washes, enabling insights into tissue-specific microbiomes. Due to the expected low microbial biomass of these samples, donor stool (when available) will also be metagenomically profiled as positive controls, which will enable us to benchmark our low-biomass processing methods with existing protocols. By sampling pediatric patients of diverse ages and health statuses, this metagenomic data will also be valuable for understanding the gut microbiome of the developing human gut across time and space. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001008081

• Genome-Wide Association Study of Schizophrenia

  The goal of the study is to find susceptibility genes for schizophrenia. Dataset versioning Version 1: European-American (EA) ancestry only Version 2: Version 1 plus African-American (AA) ancestry Consent groups and participant set General research use (GRU): 4591 cases and controls (1217 EA cases, 1442 EA controls, 953 AA cases, 979 AA controls) This consent group includes a subset of schizophrenia cases and all controls (which overlap with Bipolar study controls in Bipolar: GRU dataset). Schizophrenia and related disorders (SARC): 475 cases (187 EA cases, 288 AA cases) This consent group includes a subset of schizophrenia cases.

  Study phs000021

• Genomics from LCCC1525: A Priming Dose of Cyclophosphamide Prior to Pembrolizumab to Treat mTNBC

  This phase II, single-arm, multicenter study will evaluate pembrolizumab therapy, 200 mg IV, given every 3 weeks (Q3W), following a single priming dose of cyclophosphamide, 300 mg/m2 IV, in patients with advanced triple-negative breast cancer (TNBC) who have received at least one prior line of therapy. Data uploaded consists of FASTQ sequencing data from tumor RNASeq (pre-pembrolizumab), tumor and normal tissue WES, and sequencing for targeted T and B cell chains (TRB, IGK, IGL, IGH) from peripheral blood at various timepoints: pre-, post-, and during pembrolizumab therapy.

  Study phs002659

• The UC San Diego Chronic Lymphocytic Leukemia (CLL) Study

  The UC San Diego Chronic Lymphocytic Leukemia Study is designed to identify genetic, epigenetic, and transcriptional changes important for CLL. This data release consists of samples collected to 1) identify genomic changes associated with CLL progression using serially collected tumor samples; 2) characterize the transcriptional consequences of SF3B1 mutation through RNA-seq; and 3) characterize the expression profiles of ROR1+ vs. ROR1- tumors. The samples were collected from participants at the University of California, San Diego Moores Cancer Center and the data was generated at UC San Diego or in collaboration with the BC Cancer Agency Genome Sciences Centre.

  Study phs000767

• Adult B-precursor acute lymphoblastic leukemia RoCK and ROI single-cell transcriptome

  Whohle Transcriptome sequencing was performed following the manufactures protocol from BD Rhapsody. Capture of BCR::ABL1 was performed using RoCK and ROI. RoCK and ROI is based on barcoded beads of the BD Rhapsody platform. For RoCKseq specific capture, TSO oligos on BD Rhapsody beads are modified with a/ multiple capture sequence(s) specific to transcripts of interest. ROIseq, on the other hand, is based on specific primers which are spiked in during library generation, directing reads to regions of interest (ROIs). Multiple scRNAseq experiments were performed on several biological samples to validate RoCK and ROI.

  Study EGAS50000001366

• RNAseq profile of monomorphic epitheliotropic intestinal T-cell lymphoma and enteropathy associated T-cell lymphoma

  Background : Enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) are aggressive malignancies with limited treatment options and poor prognosis. Our research on MEITL has uncovered its genetic portrait including hallmark SEDT2 mutations, expanded its pathological spectrum, and identified molecular biomarkers influencing patients’ outcome. In this study, we aimed to establish and clarify the similar and diverging features of EATL. Methods : A large combined cohort of patients with EATL (n=30) and MEITL (n=52) was assembled and tumor samples were used for whole-exome and RNA sequencing profiling.

  Study EGAS50000001125

• High-depth whole genome sequencing of 51 premalignant breast lesions

  Ductal carcinoma in situ (DCIS) is a non-obligate precursor lesion of breast cancer, representing 20-25% of newly diagnosed breast cancer lesions. It is currently not possible to predict which DCIS patients will progress to invasive breast cancer. The samples deposited here are part of a larger study using high-depth whole-genome sequencing (WGS) to investigate the somatic mutation genomic landscape of DCIS. Comprehensive evaluation of DCIS genomes aims to uncover biological insights into breast cancer progression and potential opportunities to stratify DCIS patients for personalised treatment options or active surveillance.

  Study EGAS50000001436

• Whole Exome Sequencing of monomorphic epitheliotropic intestinal T-cell lymphoma and enteropathy associated T-cell lymphoma

  Background : Enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) are aggressive malignancies with limited treatment options and poor prognosis. Our research on MEITL has uncovered its genetic portrait including hallmark SEDT2 mutations, expanded its pathological spectrum, and identified molecular biomarkers influencing patients’ outcome. In this study, we aimed to establish and clarify the similar and diverging features of EATL. Methods : A large combined cohort of patients with EATL (n=30) and MEITL (n=52) was assembled and tumor samples were used for whole-exome and RNA sequencing profiling.

  Study EGAS50000001126

• Discordant_Monozygotic_Twins_ALS(Transcriptomics)

  Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Despite known genetic contributions to both familial and sporadic ALS cases, much of ALS heritability remains unexplained, suggesting the involvement of other genetic and epigenetic factors. To address this gap, we used a comprehensive multi-omics approach, in a pair of Italian monozygotic twins discordant for ALS, integrating DNA methylation, transcriptomics, and whole exome sequencing (WES). Here we share transcriptomic data derived from bulk RNA-seq on RNA extracted from PBMCs of the twin pair. This analysis revealed distinct transcriptomic profiles underlying the discordant disease phenotypes.

  Study EGAS50000000909

• ATACseq - Notch Signaling Maintains a Progenitor-Like Subclass of Hepatocellular Carcinoma

  To assess how Notch inhibition impacts chromatin accessibility and how chromatin changes relate to HNF4A and CEBPA activities, we performed Assay-for-Transposase-Accessible-Chromatin (ATAC) sequencing of LIV78 tumors, 72 hours after treatment with NOTCH2 blocking or control antibodies. Our TF activity and chromatin analyses thus lead to a model in which Notch inhibition leads to increased expression of CEBPA, thus enabling CEBPA to partner with HNF4A to jointly drive transcriptional programs and the underlying chromatin rearrangements that promote differentiation of progenitor-like tumor cells to a mature hepatocyte fate incompatible with tumor growth and maintenance.

  Study EGAS50000000516

• Divergent WNT Signaling and Drug Sensitivity Profiles within Hepatoblastoma Tumors and Organoids

  Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic ‘fetal’ and WNT-high ‘embryonal’, displaying divergent WNT signaling patterns. The fetal group is enriched for liver-specific WNT targets, while the embryonal group is enriched in canonical WNT target genes.

  Study EGAS50000000561

• TSO500 STJAN33, BRAF mutated CUP

  The data set contains FASTQ files (filetype) of a NEXTSEQ550DX run (instrument). De FASTQ files are from DNA and RNA sample. The Library prep is a NGS TSO500 library prep (Illumina) (technology). A Study to Examine the Clinical Value of Comprehensive Genomic Profiling Performed by Belgian NGS Laboratories: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Centre (BALLETT) This 2-year study involves the consortium of 9 cooperating Belgian NGS laboratories and will enroll 936 metastatic or locally advanced cancer patients coming from 13 different Belgian hospitals and cancer centers. Upon inclusion, all cancer patients will be offered 'comprehensive genomic profiling' (CGP) using Illumina's TSO500 NGS panel. This targeted NGS panel of 523 genes allows for the detection of single nucleotide variants, small indels, copy number variations and fusions, as well as for the determination of the 'tumor mutational burden' (TMB) and the 'microsatellite-instability' status (MSI). Both the wet lab execution of the CGP as well as the biological and clinical classification of the variants will be performed in a fully standardized way among the 9 participating Belgian local NGS laboratories.

  Dataset EGAD50000000689

• Methylation_changes_in_OA_patients_with_chronic_exposure_to_cobalt_and_chromium

  We have whole blood from a population of 70 patients, half exposed chronically to an excessof metals cobalt and chromium. The 2 groups are age, sex, and OA diagnosis matched. The2 groups have systemic differences in bone mass and turnover, and other systemicdifferences.We will type the cohort of 70 individuals on the Illumina 450k methylation array and willcompare between the two groups.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 EGAS00001001180

• TMD_AMKL_targeted_follow_up

  Genomic libraries will be generated from total genomic DNA derived from 200+ patients with childhood Transient Myeloproliferative Disorder (TMD) and or Acute Megakaryocytic Leukemia (AMKL) as well some matched constitutional samples (n < 50). Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 96 Samples will be individually barcoded and subjected to up to two lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.

  Study EGAS00001000569

• TMD_AMKL_targeted_follow_up_part_2

  Genomic libraries will be generated from total genomic DNA derived from 200+ patients with childhood Transient Myeloproliferative Disorder (TMD) and or Acute Megakaryocytic Leukemia (AMKL) as well some matched constitutional samples (n < 50). Libraries will be enriched for a selected panel of genes using a bespoke pulldown protocol. 96 Samples will be individually barcoded and subjected to up to two lanes of Illumina HiSeq. Paired reads will be mapped to build 37 of the human reference genome to facilitate the characterisation of known gene mutations in cancer as well as the validation of potentially novel variants identified by prior exome sequencing.

  Study EGAS00001000732

• Comprehensive genomic profiling of matched glioblastoma tumours, cell-lines, and xenografts reveals genomic stability and adaptation to disparate growth environments

  The mandate of this project was to use drug screening to deliver new drugs for glioblastoma (GBM) to clinical trials, and perform genomic assessment of GBM to discover new therapeutic targets and predictors of response. The sequencing data in this set was derived from GBM patient tumor samples, matched brain tumor initiating cells lines (BTICs), and tumor tissue derived from orthotopic implants.

  Study EGAS00001002709

• Role_of_Epigenetic_Memory_in_Human_Induced_Pluripotent_Stem_Cells_Pilot

  Fibroblasts have been shown to re-program into induced pluripotent stem (hiPS) cells, through over-expression of pluripotency genes. These hiPS cells show similar characteristics to embryonic stem cells including cell surface markers, epigenetic changes and ability to differentiate into the three germ layers. However it is unclear as to the extent of changes in gene expression through the re-programming process.. 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 EGAS00001000742

• Congenital_anosmia_1

  Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). To date, only a single recessive gene underlying complete anosmia has been identified. Here we sequenced the exomes of 10 individuals from a single family, including three with complete anosmia, across three generations to identify the genetic basis of congenital anosmia in this family. 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 EGAS00001001124

• Understand_Paratyphoid_Disease___host_responses_to_human_challenge_with_S__Paratyphi_A

  This project aims to evaluate the transcriptional response to disease measured in whole blood of participants who developed enteric fever after challenge and, importantly, those who were challenged but stayed well throughout the challenge period. This data will provide unique coverage of the transcriptome and will yield invaluable insight after integration with a wealth of clinical data collected during this trial. 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 EGAS00001001260

• Understanding_hematopoietic_stem_cell_mobilization_and_engraftment_

  This study looks at patients undergoing gene therapy for genetic blood and immune disorders, in particular sickle cell disease. From each patient, single blood HSPC colonies are grown from patient blood mononuclear cells, bone marrow mononuclear cells, or CD34+ at multiple time points: pre gene transduction, post-transduction, and post-infusion (at several time points). Whole-genome sequencing will be performed on DNA from these colonies and somatically-acquired mutations will be called. Using these mutations, a phylogeny of these cells can be inferred and further inferences can be made about the gene therapy transduction and engraftment steps.

  Study EGAS00001004620

• Molecular profiling of EBV associated diffuse large B-cell lymphoma

  We describe distinct molecular mechanisms leading to recurrent activation of JAK-STAT signaling, perturbation of epigenetic regulators as well as other direct targetable alterations such as PD-L1 amplification and overexpression contributing to immune evasion of lymphoma cells. Using the LymphGen 2.0 classifier, we combine data of recurrent mutations, somatic copy number alterations, and structural variants in an integrative analysis . For the first time, we reveal that less than 20% of primary EBV+ DLBCLs can be attributed to established molecular clusters of DLBCL NOS emphasizing the unique molecular character of this disease.

  Study EGAS00001006400

• COVID_19_UK_CIC_Spatial

  Understanding the immune response to SARS-CoV-2 is critical to our ability to control the coronavirus pandemic. Spatial transcriptomics will be performed on COVID-19 post-mortem tissues in collaboration with the UK - Coronavirus Immunology Consortium (UK-CIC). UK-CIC encompasses a concerted effort by the UK's world-leading immunology community to deliver a co-ordinated and agile national research programme to increase our understanding of how the immune system interacts with SARS-CoV-2. UK-CIC is led by Professor Paul Moss (University of Birmingham) and brings together 20 UK immunology centres of excellence, with support from the British Society for Immunology.

  Study EGAS00001005817

• Human Developmental Biology Resource (HDBR) abnormal fetal samples

  The HDBR (www.hdbr.org) is a human embryonic and fetal tissue bank supplying registered researchers with access to these valuable research materials up to 22 weeks post-conception (PMC4640175). All of the samples collected are analysed for chromosomal abnormalities, and all samples with an abnormal phenotype are either analysed by SNP array, or exome sequenced. This dataset is generated from those abnormal samples that have been analysed by exome sequencing. To request access to this dataset, or if any researcher is interested in obtaining tissue from any of the samples HDBR collect, please email enquiries@hdbr.org.

  Study EGAS00001006300

• Organ_maturation_in_preparation_for_birth__Peds_RFA__to_develop_a_tissue__resource_and_a_single_cell_atlas_of_organ_development_and_maturation_for__dissemination_among_the_scientific_and_clinical_community__RNA

  Knowledge about abnormal organ development is important to understand pathology and to develop novel treatment approaches for individuals with congenital and acquired disease. Most of our current understanding is based on examination of tissues from the embryo and early foetus, collected from women undergoing termination of pregnancy in the first trimester (third) of pregnancy. There is very little known about normal and abnormal organ development from a developmental perspective during the crucial last two-thirds of pregnancy when much remodelling of foetal tissues occurs. This study will generate a single-cell atlas of late-foetal lungs, blood, heart, bone and immune organs.

  Study EGAS00001008256

• MutWP5: CRUK Mutographs of Cancer: Lung: PD38234 (Targeted) (2020-01-29)

  Sequencing of LCM-derived microbiopsies from explanted lung from pulmonary fibrosis patient. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Deep sampling throughout multiple regions of the lung will determine whether there are differences in smoking-related mutation burden in different portions of the lung. Targeted sequencing will be conducted on samples to identify drivers of interest and clonality of the samples, well-performing samples will be sent for subsequent whole-genome sequencing. Results from this portion of the study will be compared to other individuals with smoking-related diseases (COPD, pulmonary fibrosis, lung cancer), and normal, non-smoking lungs. . This dataset contains all the data available for this study on 2020-01-29.

  Dataset EGAD00001005925

• WGS data for manuscript titled: Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy

  WGS data for manuscript titled: Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy

  Dataset EGAD00001008646

• Whole blood RNA sequencing of individuals from Nepal

  This study utilized blood samples collected in Lalitpur, Nepal as part of the Strategic Typhoid Alliance across Africa and Asia (STRATAA) study. The dataset comprises whole blood RNAseq of 376 febrile individuals from Nepal. Blood was collected in PAXgene tubes and sent to Monash University (Melbourne, Australia) where RNA was extracted using the PAXgene Blood RNA kit before being sent to the Wellcome Sanger Institute (Hinxton, UK) for sequencing. Library prep used NEBNext Ultra II RNA custom kits on an Agilent Bravo WS automation platform with poly(A) pulldown. After PCR, plates were purified using Agencourt AMPure XP SPRI beads and libraries were quantified using Biotium Accuclear Ultra high sensitivity dsDNA Quantitative kits. Pooled libraries were normalised to 2.8 nM. Samples were globin depleted using KAPA RNA HyperPrep with RiboErase. Libraries were then subjected to 2x100bp paired-end sequencing on Illumina NovaSeq. Each library was sequenced to an average of 80 million reads. The STRATAA study was approved by the Nepal Health Research Council (NHRC, ref 283 306/2015) and OxTREC (Oxford Tropical Research Ethics Committee, ref 39-15). All participants provided informed consent for human genetic tests.

  Dataset EGAD00001011131

• AmsterdamUMC Data Access Committee for the study entitled "Carboxylesterase 1 mediates a distinctive metabolic profile of dendritic cells to attain an inflammatory phenotype"

  The current data access committee reviews and assesses data requests of researchers that seek to gain access to data presented in the manuscript entitled "Carboxylesterase 1 mediates a distinctive metabolic profile of dendritic cells to attain an inflammatory phenotype" as performed at the AmsterdamUMC, Amsterdam, Netherlands.

  Dac EGAC50000000178

• Asan Medical Center Data Access Committee

  This DAC is responsible for reviewing and approving data access requests to protect the sensitive information of patients. The dataset includes RNA-seq data from CRLM patients treated with FOLFOX, bevacizumab, and atezolizumab, and supports research in gene expression analysis and therapeutic response. Data access requests require an approved ethical research plan, limited to projects related to cancer biology and therapy development.

  Dac EGAC50000000439

• Single-Cell Profiling of the Human Endometrium in Polycystic Ovary Syndrome: Uncovering Disease Signatures and Treatment Responses

  Single-nuclei map of human endometrial biopsies from women with and without PCOS to identify cell-type-specific disease signatures, compositional variations, and transcriptomic reversibility after a 16-week intervention with metformin or lifestyle. Single nuclei were extracted from 27 frozen endometrial biopsies for snRNA-seq using the 10X Genomics protocol.

  Dac EGAC50000000468

• Metagenomic Sequencing of Vaginal Swab and Breast Milk Samples from 173 Lifelines NEXT Participants

  This dataset contains metagenomic sequencing (MGS) data derived from vaginal swabs and breast milk samples collected from 173 participants in the Lifelines NEXT cohort. Sequencing was performed using Illumina next-generation sequencing technology, and the resulting sequence reads are provided as FASTA files for downstream microbiome analysis.

  Dataset EGAD50000002469

• Targeted capture sequencing from High-grade B-cell lymphoma, not otherwise specified: an LLMPP study

  Targeted capture sequencing for 366 newly added samples in High-grade B-cell lymphoma, not otherwise specified: an LLMPP study and 29 samples from a previously uploaded dataset.

  Dataset EGAD50000001364

• Whole genome sequencing from High-grade B-cell lymphoma, not otherwise specified: an LLMPP study

  Whole genome sequencing for 10 newly added samples in High-grade B-cell lymphoma, not otherwise specified: an LLMPP study, and 6 samples from a previously uploaded dataset.

  Dataset EGAD50000001366

• BAM files from capture-based targeted sequencing of 4 agressive B-cell lymphoma tumour samples (DLBCL-panel)

  This dataset contains BAM files from capture-based targeted sequencing of 4 agressive B-cell lymphoma tumour samples for cases 2, 3, 4 and 13. The sequencing panel used is a DLBCL-oriented panel containing 136 genes, described in Mozas P. et al., Hematol Oncol 2023.

  Dataset EGAD50000000802

• BIOMIROX

  This dataset regroups RNAseq of paired primary colorectal cancers and liver metastases extracted from 113 patients In Paris and Besançon University Hospitals. 216 FASTQ files from single-end 3' PolyA (QuantSeq 3′mRNA-Seq Kit FWD for Illumina (Lexogen)) RNAseq samples were generated On NOVASEQ 6000 (ILLUMINA).

  Dataset EGAD50000000443

• Ashkenazi Jewish Leukoencephalopathy Syndrome

  Using whole exome sequencing (WES), we identified homozygosity for a missense variant, VPS11: c.2536T>G (p.C846G), as the genetic cause of a leukoencephalopathy syndrome in two individuals from two unrelated Ashkenazi Jewish (AJ) families. Both patients exhibited highly concordant disease progression characterized by infantile onset leukoencephalopathy with brain white matter abnormalities, severe motor impairment, cortical blindness, intellectual disability, and seizures.

  Dataset EGAD00001002005

• Whole Exome Sequencing

  The Whole Exome Sequencing dataset contains 30 whole exome sequencing files (tumor, germ line DNA) and phenotype metadata for 15 patients on the phase II clinical trial of neoadjuvant immune checkpoint blockade in high-risk resectable melanoma at MD Anderson Cancer Center (NCT02519322). Included are data from baseline samples.

  Dataset EGAD00001004352

• Exome sequencing of tumor DNA samples from patients with BPLL

  DNA extracted from sorted CD19+ tumor cells (16 patients) was used for exome capture with the SureSelect V5 All Exon Kit following the standard protocols. Paired-end sequencing (2 x 100 bp) was performed using HiSeq2000 sequencing instruments. The files are in FASTQ format.

  Dataset EGAD00001004410

• Genomic stratification and liquid biopsy in a rare adrenocortical carcinoma (ACC) case, with dual lung metastases

  Dataset consisting of three WGS BAM files, representing the two dual lung metastases with matched germline control, for a 37 year old female patient, with primary adrenocortical carcinoma. Work conducted at Garvan Institute of Medical Research, Sydney, Australia.

  Dataset EGAD00001004833

• 20190219_EGA_MelanomaOnTreatment

  Illumina platform sequencing data for matched tumour-normal DNA samples from 77 melanoma patients participating in a study investigating response to immunotherapy. Selected cases also have RNA sequencing of the tumour.

  Dataset EGAD00001004869

• MGRB dataset

  This dataset comprises 2570 whole genome sequenced samples from the Medical Genome Reference Bank. https://sgc.garvan.org.au/initiatives/mgrb The files are provided in cram format, aligned to hs37d5 with decoys, with no further processing applied. The dataset also contains phenotype information for each sample.

  Dataset EGAD00001004940

• Exome sequencing of tumor DNA samples from patients with Waldenstrom macroglobulinemia

  DNA extracted from sorted CD19+ tumor cells (18 samples - 16 patients) was used for exome capture with the SureSelect All Exon Kit following the standard protocols. Paired-end sequencing (2 x 100 bp) was performed using HiSeq2000 sequencing instruments. The files are in FASTQ format.

  Dataset EGAD00001005322

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

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

  Dataset EGAD00001006353

• Small RNA sequencing from CSF extracellular vesicles - PD/CTR

  The dataset contains FASTQ files referring to the study "Small RNA sequencing from CSF extracellular vesicles - PD/CTR". For this project, RNA was isolated from CSF extracellular vesicles obtained by ultracentrifugation. Libraries were prepared with the TruSeq Small RNA library prep Illumina, and sequencing conducted in the Illumina HiSeq4000.

  Dataset EGAD00001006629

• MNM - 16S rDNA amplicon dataset of 20 dense timeseries of fecal samples from Belgian women

  Fastq files for the 16S rDNA amplicon library of 714 fecal samples of 20 time series (as described in Vandeputte et al. 2021, Nature Communications)

  Dataset EGAD00001008275

• The immunopeptidome landscape associated with T cell infiltration, inflammation and immune-editing in lung cancer

  WES sequencing of multiple regions per tumor from 8 lung cancer patients (LUSC, LCNEC and LUAD) and adjacent healthy lung tissue for each patient.

  Dataset EGAD00001008950

• bulk RNA-Seq samples of CRC patients

  The dataset contains samples of 30 CRC patients (3 samples for each patient, tumor and 2 normal adjacent tissue sites, 90 samples in total). Dataset is composed by fastq file (paired end) type from bulk RNA-Seq.

  Dataset EGAD00001009635

• CCMA-RNA

  This dataset has the raw RNA sequencing data for the cancer models in CCMA.

  Dataset EGAD00001010034

• ChIP-seq ERa and H3K27ac in endometrial healthy and tumor tissues

  ChIP-seq has been perfomed on 4 healthy and 5 tumor fresh-frozen endometrial tissues from post-menopausal patients. Immunoprecipitation has been performed for H3K27ac and ERa. Raw single-end fastq data have been aligned using bwa-mem using Hg19 genome assebly as reference. Aligment bam files are provided.

  Dataset EGAD00001010896

• Analysis of circulating miRNAs for the identification of new prognostic and predictive markers in gastro-entero-pancreatic neuroendocrine tumour (GEP-NET)

  NGS profiling of the entire miRNOme conducted on the plasma of 24 samples obtained from well-differentiated, advanced, metastatic and inoperable G1, G2 and G3 GEP-NET patients. Sequencing was performed on NexSeq platform

  Dataset EGAD00001010840

• Center for Common Disease Genomics [CCDG] - Cardiovascular: The Bangladesh Risk of Acute Vascular Events (BRAVE) Study

  The Bangladesh Risk of Acute Vascular Events (BRAVE) study is a hospital-based case-control study in Bangladesh which was established by the Cardiovascular Epidemiology Unit of Cambridge University in the UK in partnership with the key local cardiology and research centres to examine environmental, genetic, lifestyle and biochemical determinants of myocardial infarction (MI) among this South Asian population. By the end of 2016, this study has recruited ~8000 clinically confirmed first-ever MI cases (with a significant proportion being early-onset MI), and ~8000 healthy controls frequency-matched by age and sex. This site hosts data from ~500 whole genomes and ~1500 whole exomes (50% cases and 50% controls)

  Study phs001398

• A human induced pluripotent stem cell toolbox for studying sex chromosome effects -transcriptional landscape

  We use state of the art reprogramming methods to generate panels of isogenic XXY, XX and XY iPSCs from XXY patient fibroblasts. We use CRISPR/Cas9 system to evict Y chromosome from XY cells and generate XO iPSCs. The generation and characterisation of panels of isogenic XXY, XX, XY and XO iPSCs will provide a foundational toolkit to study sex differences in vitro. As iPSCs can be differentiated into any somatic cell type, we can apply the model to any human disease. We have generated bulk RNA-Seq from 12 autosomally isogenic hiPSCs to investigate transcriptional landscape and any differences in those cells in pluripotent state.

  Study EGAS50000000931

• Efficacy of two different FGFR-inhibitors in a patient with extrahepatic cholangiocarcinoma harboring an FGFR2 mutation

  Cholangiocarcinomas (CCAs) is a type of cancer with few effective systemic therapies. Elucidation of the molecular landscape of the disease from genomic studies based on next generation sequencing (NGS) has contributed to the introduction of new targeted therapies. One of these treatments consists of a class of small molecules that target members of the FGFR family of receptor tyrosine kinases. These drugs are effective and have been approved for cholangiocarcinomas with fusions or rearrangements of FGFR genes. In contrast, the role of these inhibitors in cholangiocarcinomas with mutations in FGFR genes is less well defined. We report here a patient with a cholangiocarcinoma bearing a FGFR2 p.Ser252Trp mutation. The patient was treated with two different FGFR inhibitors, as the first caused ocular toxicity. She obtained clinical benefit from both. This case illustrates the efficacy of FGFR inhibitors on cholangiocarcinoma with specific point mutations. This is the first case to report the clinical benefit of these drugs in FGFR2 p.Ser252Trp mutation. Clinical benefit can be sustained, as seen in our patient. Our case also shows that FGFR inhibitors-induced adverse effects, such as ocular toxicities, may not recur after re-challenge with an alternative drug of the same class.

  Dataset EGAD50000000021

• Tobacco exposure and somatic mutations in normal human bronchial epithelium

  That tobacco smoking causes lung cancer is well-established, but we lack quantitative understanding of its effects on genomes of normal bronchial epithelium. We sequenced whole genomes of 632 colonies derived from single bronchial epithelial cells across 16 subjects. Tobacco smoking is the major influence on mutation burden, adding 1000-10,000+ mutations/cell, massively increasing both between-subject and within-subject variance, and generating several distinct signatures of substitutions and indels. A population of cells in subjects with smoking history had mutation burdens equivalent to that expected for never-smokers: these cells lacked tobacco-specific mutational signatures, were four-fold more frequent in ex-smokers than current smokers, and had significantly longer telomeres than their more mutated counterparts. Driver mutations increased in frequency with age, affecting 4-14% of cells in middle-aged never-smokers. In current smokers, ≥25% of cells carried driver mutations and 0-6% cells had 2 or even 3 drivers. Thus, tobacco smoking increases mutation burden, cell-to-cell heterogeneity and driver mutations, but quitting promotes replenishment of bronchial epithelium from mitotically quiescent cells that have avoided tobacco mutagenesis.

  Dataset EGAD00001005193

• Center for Common Disease Genomics (CCDG) - Cardiovascular: Emory Cohort

  The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex inherited diseases. This study contains variant calls derived from the whole genome sequence data of an early-onset coronary artery disease case-control cohort selected from Emory University Cardiovascular Biobank. Case status was assigned based on the presence of myocardial infarction, coronary artery stenosis greater than 70% in at least one coronary artery, and/or revascularization (coronary angioplasty with or without stent placement or coronary artery bypass grafting) at an early age. For these samples "early age" is defined as men 60 years of age or younger and women 70 years of age or younger. The National Human Genome Research Institute (NHGRI) has funded the Centers for Common Disease Genomics (CCDG), a collaborative large-scale genome sequencing effort to comprehensively identify rare risk and protective variants contributing to common disease phenotypes and to better understand the general principles of genomic architecture underlying common, complex inherited diseases.

  Study phs001880

• Rapid Acceleration of Diagnostics - Underserved Populations (RADx-UP): COVID-19 Testing and Vaccination Social Network Diffusion for Diverse Criminal Legal Involved Communities

  This RADx-UP Phase II proposal, "Social network diffusion of COVID-19 prevention for diverse Criminal Legal Involved Communities", will implement a situation appropriate COVID-19 testing and vaccination social network diffusion intervention - C3 - building upon RADx-UP Phase I lessons and successful social network prevention interventions developed previously by the research team. C3 Criminal Legal Involved (CLI) populations encompass those non-incarcerated who have experienced recent arrest, incarceration, probation, parole or diversion programs such as drug courts. While increases in COVID-19 testing have been observed among this group, there remain members with limited testing history as well as individuals who are vaccine hesitant. COVID-19 prevention messaging can no longer be simplified to "everyone test and/or everyone vaccinate" as testing and vaccination decisions among community members are sensitive to personal histories (i.e., prior infection), local infection rates (i.e., low rates) and testing/vaccination availability. As COVID-19 prevention efforts have become more complicated (i.e., test if exposed), people tend to focus on the messenger, and particularly those that are close to them. Personal connections and communications within existing personal network structures, such as families, friends and other trusted acquaintances represent the cornerstone to increase situation appropriate testing and overcoming COVID-19 vaccine hesitancy. C3 builds upon RADx-UP I, by using a network diffusion approach facilitated through motivational interviewing purposefully geared to mobilize one's own organic social network to increase context appropriate testing and vaccine uptake. Through this process we will maximize the primary benefit and impact of this type of intervention which also has the intended effect of increasing likelihood that the messenger themselves will undergo the same behavior change that they have been trained to promote. We will leverage infrastructure developed in RADx-UP Phase I, which includes 4 high-impact sites across the Central US from Phase I: Baton Rouge LA, Little Rock AR, Indianapolis IN, and Chicago IL. We will utilize established engagement efforts already in place and continue to fully integrate communities in the strategic application of the intervention. We will use the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework to guide implementation. C3 aims to: Aim 1a. Test the efficacy (3-month situation appropriate testing or vaccination) of a network diffusion intervention (C3) versus an existing COVID-19 testing and vaccine linkage to care intervention among: 1) primary study participants (primary outcome); and 2) secondary study participants connected to primary participants (secondary outcome) using a RCT design. Aim 1b. Explore the mechanisms for differential intervention effects at the individual and network-level that may increase situation appropriate testing and/or vaccination uptake. Aim 2. Examine key RE-AIM components in real time tied to the implementation of the network diffusion intervention (C3).

  Study phs003234

• Illumina HumanCoreExome genotyping data from the British Society for Surgery of the Hand Genetics of Dupuytren’s Disease consortium (BSSH-GODD consortium) collection

  Dupuytren's Disease (DD - OMIM126900) is the most common heritable disorder of connective tissue. It is a fibroproliferative disorder of the palmer fascia, causing flexion contractures of affected digits. DD affects men more commonly than women. DD is an archetypal complex disease, with multiple genetic and environmental factors affecting the final expression of the disease phenotype. The incidence increases with age, and the prevalence of DD is therefore increasing as the UK population ages. Half of all patients present before age 60. DD causes significant functional impairment, and severe contractures can lead to permanent disability. The mainstay of current treatment is surgery, but recurrence and complications are both high. For severe contractures, the only suitable treatment option is amputation. The direct costs to the NHS are high, and underestimate the true economic costs to society. We collected salivary samples from adults in the UK who have had surgery for DD. We have genotyped these samples using the Illumina HumanCoreExome Beadchips. https://research.ndorms.ox.ac.uk/public/dupuytrens/what-is-dupuytrens-disease/

  Study EGAS00001001206

• Short-term fasting before living kidney donation has an immune-modulatory effect

  Background: Short-Term Fasting (STF) is an intervention reducing the intake of calories, without causing undernutrition or micronutrient-related malnutrition. It aims to systemically improve resilience against acute stress. Several (pre-)clinical studies have suggested protective effects of STF, marking the systemic effects STF can induce in respect to surgery and ischemia-reperfusion injury. In addition, STF also affects the number of circulating immune cells. We aim to determine the effect of STF on the abundance and phenotype of different immune cell populations. Methods: Thirty participants were randomly selected from the FAST clinical trial, including living kidneys donors, randomised to a STF-diet or control arm. In an observational cohort sub-study we prospectively included 30 patients who donated blood samples repeatedly during study runtime. Using flow cytometry analyses, immune cell phenotyping was performed on peripheral blood mononuclear cells. Three panels were designed to investigate the presence and activation status of peripheral T cells, B cells, dendritic cells (DCs) and myeloid cells. Results: Eight participants were excluded due to sample constraints. Baseline characteristics showed no significant differences, except for fasting duration. Weight changes were minimal and non-significant across different time intervals, with slight trends towards long-term weight loss pre-surgery. Glucose, insulin, and β-hydroxybutyrate levels differed significantly between groups, reflecting adherence to the fasting diet. Flow cytometry analysis revealed no baseline differences between groups, with high variability within each group. We observed significant changes in immune cell populations due to fasting, particularly in B cells, T cells, and DCs. Discussion: In this study, we found that STF changes the levels and phenotype of immune cells, reducing abundance and activation of T cells and regulatory T cells, increased presence of (naïve) B cells, and elevation of type 1 conventional DCs. Further research should focus on the clinical implications of the changes in immune cell populations and significance of these observed immunological changes. Background: Short-Term Fasting (STF) is an intervention reducing the intake of calories, without causing undernutrition or micronutrient-related malnutrition. It aims to systemically improve resilience against acute stress. Several (pre-)clinical studies have suggested protective effects of STF, marking the systemic effects STF can induce in respect to surgery and ischemia-reperfusion injury. In addition, STF also affects the number of circulating immune cells. We aim to determine the effect of STF on the abundance and phenotype of different immune cell populations. Methods: Thirty participants were randomly selected from the FAST clinical trial, including living kidneys donors, randomised to a STF-diet or control arm. In an observational cohort sub-study we prospectively included 30 patients who donated blood samples repeatedly during study runtime. Using flow cytometry analyses, immune cell phenotyping was performed on peripheral blood mononuclear cells. Three panels were designed to investigate the presence and activation status of peripheral T cells, B cells, dendritic cells (DCs) and myeloid cells. Results: Eight participants were excluded due to sample constraints. Baseline characteristics showed no significant differences, except for fasting duration. Weight changes were minimal and non-significant across different time intervals, with slight trends towards long-term weight loss pre-surgery. Glucose, insulin, and β-hydroxybutyrate levels differed significantly between groups, reflecting adherence to the fasting diet. Flow cytometry analysis revealed no baseline differences between groups, with high variability within each group. We observed significant changes in immune cell populations due to fasting, particularly in B cells, T cells, and DCs. Discussion: In this study, we found that STF changes the levels and phenotype of immune cells, reducing abundance and activation of T cells and regulatory T cells, increased presence of (naïve) B cells, and elevation of type 1 conventional DCs. Further research should focus on the clinical implications of the changes in immune cell populations and significance of these observed immunological changes.

  Study EGAS00001008034

• Kids First: Whole Genome Sequencing of Nonsyndromic Craniosynostosis

  The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the WGS and phenotypic data from this study are accessible through dbGaP and kidsfirstdrc.org, where other Kids First datasets can also be accessed. Nonsyndromic craniosynostosis (NCS) is a common, major structural birth defect - due to the premature fusion of one or more cranial sutures - that requires extensive surgical correction and is associated with considerable ongoing medical problems and health care costs. Because little is known about the causes of NCS, whole genome sequencing will help advance knowledge of genetic factors contributing to the etiology of NCS. Data from this project will lead to a better understanding of biological processes involved in the etiology of NCS and provide critical insights for development of early diagnostic tools and therapeutic strategies.

  Study phs001806

• Single Duplex DNA Sequencing with CODEC Detects Mutations with High Sensitivity

  Detecting mutations from single DNA molecules is crucial in many fields but challenging. Next generation sequencing (NGS) affords tremendous throughput but cannot directly sequence double-stranded DNA molecules (single duplexes) to discern the true mutations on both strands. Here, we present Concatenating Original Duplex for Error Correction (CODEC) which confers single duplex resolution to NGS. CODEC affords 1,000-fold higher accuracy than NGS, using up to 100-fold fewer reads than Duplex Sequencing. CODEC revealed mutation frequencies of 2.72 x 10-8 in sperm of a 39-year-old individual, and somatic mutations acquired with age in blood cells. CODEC detected genome-wide clonal hematopoiesis mutations from single DNA molecules, single mutated duplexes from tumor genomes and liquid biopsies, microsatellite instability (MSI) with 10-fold greater sensitivity, and mutational signatures and specific tumor mutations with up to 100-fold fewer reads. CODEC enables more precise genetic testing and reveals biologically significant mutations which are commonly obscured by NGS errors. We applied CODEC to clinical colon and breast neoplasm samples and uncovered expected mutational signatures including homologous recombination deficiency (HRD) and MSI.

  Study phs003255

• Single-Cell Transcriptomic Analysis of Kaposi Sarcoma

  Summary: Single-cell transcriptome analysis of skin and blood samples from individuals with Kaposi's sarcoma Aims: Elucidate the cellular composition and gene expression profiles of Kaposi sarcoma herpesvirus (KSHV) infected cells and non-infected tumor infiltrating cells, and peripheral blood samples from the same individuals, with or without specific therapies, such as antiretroviral therapy for HIV, immunotherapies (such as immune checkpoint inhibitors and immune modulator drugs like pomalidomide), or angiogenesis inhibitory agents. Population: Age 18 and older, both genders, including individuals from North America and other areas of the world (including Africa). Individuals with or without HIV are included. Molecular Technologies: Single-cell RNAseq using 10x Genomics Principal Findings: Two distinct populations of endothelial cells were found infected with KSHV, one CD34+ and one CD34-Both clusters include lytic and latent KSHV gene expressionThe KSHV infected cell clusters differ in expression of housekeeping genes, proliferative markers, ribosomal and secretory vesicle genesBiomarkers of KSHV infected cells were identified, including sodium channel SCN9A Changes in cell composition with therapy are noted Clonal amplification of TCR+ T-cells were noted in the skin and blood Data Available through dbGaP: scRNA-seq data

  Study phs003800

• Novel regional age-associated DNA methylation changes within human common disease-associated loci

  Background: Advancing age progressively impacts on risk and severity of chronic disease. It also modifies the epigenome, with changes in DNA methylation, due to both random drift and variation within specific functional loci. Results: In a discovery set of 2,238 peripheral-blood genome-wide DNA methylomes (MeDIP-seq) aged 19-82 years, we identified 71 age-associated Differentially Methylated Regions (a-DMRs, p < 1.85 x 10-8) within the Linkage Disequilibrium (LD) blocks of the NIH Catalogue of published GWAS SNPs. This included 52 novel regions, 29 within loci not covered by 450k or 27k Illumina array, and with marked enrichment for Poised Promoters and Enhancers across multiple cell types. In a replication set of 2,084 DNA methylomes, 95.7% of the a-DMRs showed the same direction of ageing effect, with 80.3% and 53.3% replicated to p < 0.05 and p < 1.85 x 10-8, respectively. Conclusion: By analysing the functionally enriched disease and trait-associated regions of the human genome, we identified novel epigenetic ageing changes, which could be useful biomarkers or provide mechanistic insights into age-related common diseases.

  Study EGAS00001001910

• Transcriptomes of human CD4+ T lymphocytes - Metabolic project

  Human CD4+ T cells are essential mediators of immune responses. By altering the mitochondrial and metabolic states, we defined metabolic requirements of human CD4+ T cells for in vitro activation, expansion, and effector function. T cell activation and proliferation were reduced by inhibiting oxidative phosphorylation, while early cytokine production was maintained by either OXPHOS or glycolytic activity. Glucose deprivation in the presence of mild mitochondrial stress markedly reduced all three T cell functions, contrasting the exposure to resveratrol, an antioxidant and sirtuin-1 activator, which specifically inhibited cytokine production and T cell proliferation, but not T cell activation. Conditions that inhibited T cell activation were associated with the downregulation of 2′,5′-oligoadenylate synthetase genes via interferon response pathways. Our findings indicate that T cell function is grossly impaired by stressors combined with nutrient deprivation, suggesting that correcting nutrient availability, metabolic stress and/or the function of T cells in these conditions will improve the efficacy of T cell-based therapies.

  Study EGAS00001005565

• Single-nucleus transcriptomic profiling of aging Down Syndrome brains

  Down syndrome (DS) – trisomy of human chromosome 21 (HSA21) – is characterized by lifelong cognitive impairments and development of neuropathological hallmarks of Alzheimer’s disease (AD). The cellular and molecular modifications responsible for these effects are not understood. Here we performed single-nucleus RNA-sequencing (snRNA-seq) employing both short (Illumina) and long-read (Pacific Biosciences) sequencing technologies on a total of 29 DS and non-DS control prefrontal cortex samples. In DS, the ratio of inhibitory-to-excitatory neurons was significantly increased, which was not observed in previous reports examining sporadic AD. DS microglial transcriptomes displayed AD-related aging and activation signatures in advance of AD neuropathology, with increased microglial expression of C1q complement genes (associated with dendritic pruning) and the HSA21 transcription factor gene RUNX1. Long-read sequencing detected vast RNA isoform diversity within and amongst specific cell types including numerous novel sequences that differed between DS and normal brains. Notably, over 8,000 genes produced RNAs containing intra-exonic junctions (IEJs), including APP that had previously been associated with somatic gene recombination. These and related results illuminate large-scale cellular and transcriptomic alterations as novel features of the aging DS brain.

  Study EGAS00001005691

• BARIA baseline first 100 individuals transcriptomes

  Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples. Methods The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years.

  Study EGAS00001005704

• Targeted sequencing of diffuse large B-cell lymphoma tumour samples from the UK's Haematological Malignancy Research Network

  The UK’s Haematological Malignancy Research Network (www.HMRN.org) was established in 2004 to provide robust generalizable data to inform clinical practice and research. HMRN is a collaboration between researchers in the Epidemiology & Statistics Group (ECSG) at the University of York, a unified Clinical Network operating across 14 hospitals, and an integrated Haematological Malignancy Diagnostic Service (HMDS) in Leeds. Covering a population of around 4 million, HMRN collects detailed information about all patients diagnosed with a haematological malignancy within the HMRN region, accruing around 2,400 new diagnoses each year. The population has a similar socio-demographic profile to the country as a whole, and HMRN’s maturing data present an increasingly valuable resource to address real questions of concern to haematologists, commissioners and health service researchers – locally, nationally and internationally. This study forms part of a larger project employing targeted exome sequencing on tumour samples from patients diagnosed with a variety of both lymphoid and myeloid malignancies. The results for samples collected from 928 diffuse large B-cell lymphoma patients, diagnosed within HMRN from 2005 to 2012, are provided.

  Study EGAS00001005953

• High-Resolution Spatial Transcriptomics Uncover Epidermal-Dermal Divergences in Merkel Cell Carcinoma: Spatial Context Reshapes the Gene Expression Landscape

  Merkel cell carcinoma (MCC) is an aggressive malignancy with neuroendocrine differentiation marked by high plasticity, often manifesting as rapid therapy resistance. Although the cell-of-origin is presumed to be epithelial, epidermal localization of MCC is rarely observed, largely because in situ MCC is typically an incidental finding. Nevertheless, a subset of MCC tumors exhibits epidermotropism, wherein tumor cells are present in the epidermis. The behavior of cancer cells is profoundly influenced by the tumor microenvironment and interactions with neighboring cells. Notably, the normal counterparts of the cancer’s cell-of-origin have been shown to attenuate tumor aggressiveness. Thus, epidermotropic MCC presents a unique opportunity to explore the potential role of surrounding keratinocytes in modulating tumor cell behavior. While the epidermotropic tumor nests share histological resemblance with their dermal counterparts, their transcriptomic profiles remain unexplored. Here, we employed high-definition spatial and single cell transcriptomics to dissect the gene expression profiles of epidermotropic MCC cells, comparing them to MCC cells in the tumor core and those adjacent to blood vessels. Notably, epidermotropic MCC cells exhibit a transcriptomic signature reminiscent of cutaneous squamous cell carcinoma, characterized by upregulation of genes encoding keratins, S100A proteins, as well as calmodulin-like proteins 3 and 5. Mechanistically, this keratinocytic differentiation is associated with enhanced p63 activity, leading to the upregulation of PERP. Collectively, our study demonstrates that MCC cells can adopt a keratinocytic differentiation program in response to microenvironmental cues, underscoring the remarkable phenotypic plasticity of this malignancy and the importance of the tumor microenvironment for tumor characteristics.

  Study EGAS00001008157

• RNA isoform repertoire of neuropsychiatric risk genes in human brain

  Neuropsychiatric disorders are highly complex conditions and the risk of developing a disorder has been tied to hundreds of genomic variants that alter the expression and/or products (isoforms) made by risk genes. However, how these genes contribute to disease risk and onset through altered expression and RNA splicing is not well understood. Here we show our current understanding of gene isoforms is far from complete and reveal the precise splicing profiles of neuropsychiatric disorder risk genes. Combining our new bioinformatic pipeline IsoLamp with nanopore long-read amplicon sequencing, we deeply profiled the RNA isoform repertoire of 31 high-confidence neuropsychiatric disorder risk genes in human brain. We show most risk genes are more complex than previously reported, identifying 443 novel isoforms and 28 novel exons, including isoforms which alter protein domains, and genes such as ATG13 and GATAD2A where most expression was from previously undiscovered isoforms. The greatest isoform diversity was present in the schizophrenia risk gene ITIH4. Mass spectrometry of brain protein isolates confirmed translation of a novel exon skipping event in ITIH4, suggesting a new regulatory mechanism for this gene in brain. Our results emphasize the widespread presence of previously undetected RNA and protein isoforms in brain and provide an effective approach to address this knowledge gap. Uncovering the isoform repertoire of neuropsychiatric risk genes will underpin future analyses of the functional impact these isoforms have on neuropsychiatric disorders, enabling the translation of genomic findings into a pathophysiological understanding of disease.

  Study EGAS00001007744

• HCA_Thymus_Disease_DiGeorge_Transplant_RNA

  Single cell transcriptomics study of thymic transplant biopsies Allogeneic thymus transplantation is the only curative therapy for complete DiGeorge Syndrome (cDGS), a rare severe primary immunodeficiency characterised by athymia. GOSH is one of only two centres worldwide to offer this treatment. Despite a lack of major histocompatibility complex (MHC)-matching between donor and host, transplanted thymus becomes repopulated by recipient bone marrow derived precursor cells and supports development of functional T-cells. The mechanisms underlying thymopoiesis in this context are poorly understood, but over time we observe reconstitution of T-cell immunity, with the ability to produce host naïve T-cells showing a broad T-cell receptor (TCR) repertoire and to generate MHC-restricted T-cell proliferative responses. Although lifesaving, the achieved immunological reconstitution is typically not complete with circulating T-cell numbers usually remaining below the age related normal ranges. Additionally, we observe persistence of donor-derived T-cells of unknown clinical significance. To gain more insight into the mechanisms by which MHC-mismatched transplanted thymus supports T-cell development with self-tolerance, as well as into the basis of suboptimal T-cell immunity, we now aim to investigate immune reconstitution after thymus transplantation in further detail by using single-cell transcriptomics, applied to thymic transplant biopsies and peripheral blood samples collected during standard post-transplant patient care. By identifying which lineages of host- derived cells repopulate the thymic tissue after transplantation, we will be able to address the role of MHC in positive and negative T-cell selection during T-cell differentiation. We will also be able to clarify the exact ontogeny of the persistent donor T-cells, as well as their possible role. Understanding the mechanisms of action of HLA-mismatched transplanted thymus will contribute to treatment optimisation. Additionally, our research provides a unique opportunity to further investigate key immunological concepts, such as tolerance and autoimmunity, challenging existing paradigms in thymus immunology. 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 EGAS00001004025

• Chromatin remodeling enhances MAP3K8 expression in HAM: a key pathogenesis for therapeutic intervention

  Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM) is a debilitating neuroinflammatory disease with no available effective treatments. A hallmark of HAM is the transformation of HTLV-1-infected cells into T helper type 1 (Th1)-like cells, characterized by excessive interferon (IFN)-gamma production that drives chronic inflammation. However, the molecular mechanisms fuel this aberrant Th1-like transformation and sustained inflammation remain poorly understood. We hypothesized that HAM-characteristic chromatin remodeling plays a pivotal role in the overexpression of key genes driving inflammatory pathogenesis. Using transcriptomic analysis, chromatin accessibility profiling, and biomarker evaluations across HTLV-1-related diseases, we identify MAP3K8 as a key gene that defines the unique inflammatory profile of HAM. MAP3K8 overexpression promotes Th1-like differentiation and constitutively activates the MEK-ERK signaling pathway. Furthermore, we elucidate the mechanism by which HTLV-1 Tax, Fosl2, and c-Jun collaboratively induce HAM-characteristic chromatin remodeling at the enhancer region of the MAP3K8 locus. Crucially, we demonstrate that mitogen-activated protein kinase kinase (MEK) inhibitors effectively suppress the MAP3K8-MEK signaling cascade and significantly mitigated inflammatory pathogenesis in an ex vivo culture assay. Our findings provide critical insights into the virus-host interactions underpinning HAM and propose the MAP3K8-MEK-ERK axis as a promising therapeutic target for this challenging condition.

  Study JGAS000835

• Emergence of oncofetal plasticity is ubiquitous in early colorectal cancers

  Metastasis formation is classically considered a late-stage event in colorectal cancer (CRC) evolution. Yet, the time and patterning by which metastatic competence is acquired remain poorly understood. Here, we show that metastasis-associated oncofetal cell states already emerge at the earliest stages of CRC, concurrent with invasive front formation. However, while necessary for metastasis, we detect them ubiquitously among early non-metastatic cancers, highlighting additional bottlenecks like immune evasion. To understand how oncofetal cells first emerge, we generated multiregional organoid models that reflect successive tumor progression stages within individual early-stage CRCs. Whole-genome sequencing and growth factor-dependency assays exclude tumor cell-intrinsic acquired traits. In contrast, single-cell spatial atlases of the tumor-microenvironment before and after malignant transformation revealed stereotypic patterning of fibroblast subtypes resembling normal tissue architecture, resulting in distinct regional microenvironments. At the onset of malignant growth into the submucosa, the first cancer-associated fibroblasts (CAFs) to appear strongly resemble submucosal trophocytes and colocalize with oncofetal cell states at invasive fronts. Functionally, fibroblast-organoid co-cultures confirm that these trophocyte-like CAFs induce plastic transitioning to oncofetal states. Thus, interactions between tumor and submucosal fibroblasts directly following malignant transformation dictate the timing and location at which oncofetal plasticity first occurs during CRC progression.

  Study EGAS50000001532

• Large Scale Genotyping of Psychiatric Disorders

  Psychiatric disorders cause enormous human suffering and cost to society. The goal of this project is to elucidate the genetics of psychiatric disorders through a large consortium effort and genome-wide genotyping. The Psychiatric Genomics Consortium (PGC) (https://www.med.unc.edu/pgc) is an international consortium to pursue genome-wide analyses of common psychiatric disease. The PGC was founded in 2007 to unite investigators from around the world to conduct mega-analyses of individual genome-wide genotype data for schizophrenia (SCZ), bipolar disorder (BIP), autism (AUT), attention-deficit hyperactivity disorder (ADHD), and major depressive disorder (MDD). Subsequently, the PGC has expanded to include Tourette syndrome (TS), obsessive-compulsive disorder (OCD), eating disorders (ED), post-traumatic stress disorder (PTSD), and substance abuse (SUD). The PGC partnered with Illumina to develop the PsychChip, a custom GWAS array aimed at capturing common variation genome-wide for imputation, rare coding variation drawn from the exome chip and dense genotypes for loci with suggestive evidence for association across the initial PGC analyses of SCZ, MDD, BPD, ASD and ADHD. Samples (cases, controls, and families) were collected from Institutional Review Board-approved protocols that aim to study the genetics of psychiatric disorders. Genome-wide genotyping was performed at the Broad Institute (Cambridge, MA, USA) and the Mount Sinai School of Medicine Friedman Brain Institute (New York, NY, USA) using the PsychChip or Exome Chip.

  Study phs001413

• Organoid BulkRNAseq

  Here, we aim to understand early determinants of brain organoid quality and generated a set of brain organoids from 12 different hPSC lines using an adaptation of the unguided Lancaster protocol (Lancaster & Knoblich, 2014). All cell lines were obtained from healthy donors. 12 donor hPSC lines were differentiated into brain organoids and a set of 72 individual organoids (6 per line) were randomly selected morphologically diverse organoids and subjected to bulk RNA sequencing for gene expression analysis. RNA was extracted using the RNeasy kit (Qiagen, Germany) according to the manufacturer’s instructions. A total of 1000 ng per sample was sent for RNA sequencing to Azenta Life Sciences (Genewiz Leipzig, Germany) for sequencing. Library preparation was performed using the NEBNext Ultra II RNA Library Prep Kit for Illumina following manufacturer’s instructions (NEB, Ipswich, MA, USA). mRNAs were first enriched with Oligo(dT) beads. The samples were sequenced using a 2x150 Pair-End (PE) configuration v1.5 at a depth of >20 million reads in each sample. Raw sequence data (.bcl files) generated from Illumina NovaSeq6000 was converted into fastq files and de-multiplexed using Illumina bcl2fastq program version 2.20. The raw sequence reads were aligned to the human reference genome GRCh38 using the STAR aligner (Dobin et al., 2013). Gene expression levels were quantified using the FeatureCounts tool (Liao et al., 2014).

  Study EGAS50000000659

• Neoadjuvant Trastuzumab Response in Breast Cancer

  HER2 (ERBB2) gene amplification and overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents such as trastuzumab are effective treatments, therapeutic resistance remains a concern in HER2-positive breast cancer with 40-50% of patients having residual disease after neoadjuvant treatment with chemotherapy and trastuzumab. To investigate features that may make it possible to predict at diagnosis which cancers will be responsive to trastuzumab and chemotherapy, 48 tumor/normal DNA pairs extracted from pretreatment tumor biopsies and blood of HER2-positive breast cancer cases treated with neoadjuvant chemotherapy and trastuzumab were sequenced. Whole genome and exome sequence from tumor (average depth 49x and 71x) and normal (average depth 33x and 69x) DNA are included here as well as RNAseq data for 42 of the tumors. The study cohort was equally divided between patients who experienced pathological complete response and those with residual disease. Samples were obtained from the American College of Surgeons Oncology Group Z1041 trial (NCT00513292) and a local single-institution study (NCT00353483).

  Study phs001291

• CPTAC: Molecular Dissection of Chemotherapy Response in Triple Negative Breast Cancer

  Sporadic Triple Negative Breast Cancer (TNBC) represents 10-15% of breast cancers (BC) worldwide. Non-specific chemotherapy remains the standard of care as there are no targeted agents. In 50% of cases, pathological complete response (pCR) is not achieved, and these individuals experience poor survival. Predictive markers for chemotherapy have proved elusive, and patients can receive up to five different chemotherapy agents to optimize outcomes. Microscaled proteogenomics (PMID: 31988290) is a discovery technique that integrates DNA and RNA sequencing with mass spectrometry based proteomics. This approach was applied to snap-frozen biopsies obtained before TNBC treatment on a clinical trial of carboplatin and docetaxel. Proteogenomic profiling included whole exome sequencing (WES), RNA-seq, and tandem mass tag based proteomics and phosphoproteomics.The study was approved by the IRB at both participating sites: Washington University in St. Louis and Baylor College of Medicine (BCM), and followed the Declaration of Helsinki and Good Clinical Practice guidelines. The protocol and informed consent documents were approved by Washington University School of Medicine (WUSM) and BCM.

  Study phs002505

• Multi-omic analysis of cell-of-origin and epigenomic state in pediatric H3K27M gliomas

  It is not known whether midline pediatric gliomas driven by Histone 3 K27M mutations (oncohistones) or EZHIP expression (oncohistone-mimics) share a common cell-of-origin, or arise from distinct cell types with unique vulnerabilities to PRC2 inhibition and partner alterations. Here, we define the etiological and oncogenic relationship between pediatric midline gliomas characterized by inhibition of K27M and K27M-like oncohistones. We assemble an extensive reference for gliogenesis from the developing mouse and human fetal brain. With bulk and single-cell transcriptomics and epigenomics, we profiled a large cohort of primary tumors comprising H3.1K27M and H3.3K27M pontine gliomas, H3.3K27M thalamic gliomas, and EZHIP+ posterior fossa ependymomas. We focus on differences across axes of location (thalamus vs. pons vs. posterior fossa), tumor type (diffuse midline gliomas vs. ependymomas), and oncohistone (H3.1/2K27M vs. H3.3K27M vs. EZHIP). We use tumor molecular features to delineate transcriptional states and cell-of-origin in each entity. Finally, we use culture models in isogenic contexts to interrogate the effect of each oncohistone or mimic.

  Study EGAS00001005773

• “Castration-persistence” is a distinct state of tolerance to androgen receptor targeting therapies in prostate cancer

  Androgen receptor (AR) signalling is important in prostate cancer progression, and therapies that specifically target this pathway are the mainstay of treatment for advanced disease. Treatment however is non-curative, and resistance develops inevitably with time. Although the mechanisms that drive progressive ‘castration resistant’ disease are reasonably well characterized, how tumours survive acute pathway inhibition is unclear. We performed a neo-adjuvant study of a novel combination of AR targeting therapies, and noted that the objective response to treatment was highly variable. To determine what was driving tumour persistence in poorly responding patients, we comprehensively characterised pre- and post-treatment samples were using both whole genome and RNA-sequencing. We find that ‘castration-persistence’ is a distinct state from ‘castration-resistance’, and is mediated by global transcriptional reprogramming leading to transitional EMT state, which is shared with benign luminal epithelial cells. This appears to be AP-1 and KLF driven, and represents and integration of multiple signalling pathways, particularly IGF2, offering a number of tractable strategies to improve clinical response to AR targeting therapies.

  Study EGAS00001003172

• North Carolina Clinical Genomic Evaluation by NextGen Exome Sequencing (NCGENES)

  North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing This study is part of a larger consortium project investigating the validity and best use of next-generation sequencing (in particular, whole exome sequencing, or WES) in clinical care. Participants are patients who were either seen in the UNC Cancer and Adult Genetics Clinic or referred to the study by their physician. They will be approached by their physician or a genetic counselor for recruitment. Once enrolled, a clinical geneticist or genetic counselor will obtain consent and collect blood samples to be analyzed using WES. Results may include information related to a diagnosis and incidental information. Medically actionable incidental findings will be CLIA-certified and returned to participants in a routine genetic counseling session, along with diagnostic findings. Eligible adult participants will be randomized to have the opportunity to choose to get certain types of non-medically actionable incidental findings, as well. Their decisions will be investigated, as will psychosocial and behavioral responses to sequencing and receiving sequencing information. This is a longitudinal, mixed methods study (i.e., multiple assessments pre- and post-return of results, with both quantitative and qualitative methods used to gather data). Because only the quantitative component of the study uses randomization, only measures and procedures associated with that component are included here. The third study release includes data of additional n=189 subjects.

  Study phs000827

• National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) Consortium Glaucoma Genome-Wide Association Study: Whole Exome Resequencing in Glaucoma

  This is a study of primary open angle glaucoma (POAG) conducted through exome sequencing of cases and comparison of variant frequencies with general population frequencies available in dbGAP and controlled for sequencing platform artifact to minimize false positives. POAG is an intraocular pressure (IOP) related progressive optic neuropathy that ultimately leads to blindness. This study builds upon the efforts of an on-going collaborative consortium that studied 2,170 POAG cases and 2,347 controls with a unified definition of POAG (the NEIGHBOR consortium: NEI Glaucoma Human genetic collaBORation). The case definition for NEIGHBOR was harmonized with an additional 976 cases and 1140 controls from the NHGRI supported GENEVA (gene-environment) study of glaucoma (GLAUGEN) (NIH/NHGRI U01HG004728, Pasquale PI). In NEIGHBOR, cases and controls were recruited from ophthalmology clinics and were examined by ophthalmologists. For cases, the clinical exam included intraocular pressure measurements, optic nerve assessment and visual field evaluation. Controls had no family history of glaucoma, normal intraocular pressure and normal optic nerves. Cases and controls were also drawn from two clinical trial populations: Advanced Glaucoma Intervention Study (AGIS, NEI U10EY006827, D. Gaasterland PI) and Collaborative Initial Glaucoma Treatment Study (CIGTS, NEI U10 EY009149, P. Lichter PI). The Glaucoma Exome Sequencing study has one Principal Investigator: Theresa Gaasterland (UCSD) and two Co-Investigators: Robert Weinreb, MD, and Kang Zhang, MD, PhD, all of whom are part of the NEIGHBOR, subsequently NEIGHBORHOOD, consortium, which in turn has two Co-Principal Investigators: J. Wiggs (Harvard, MEEI), and M. Hauser (Duke). NEIGHBOR collaborators who contributed samples and/or expertise to the Glaucoma Exome Sequencing study included the following: Harvard Medical School (Massachusetts Eye and Ear Infirmary) (J. Wiggs, L. Pasquale); Duke University Medical Center (M. Hauser, E. Hauser, R. Allingham, S. Schmidt); University of Michigan (J. Richards, S. Moroi, P. Lichter); University of Miami (M. Pericak-Vance, R. Lee, D. Budenz); Vanderbilt University (J. Haines); University of California San Diego (K. Zhang, R. Weinreb; T. Gaasterland); University of Pittsburgh (J. Schuman, G. Wollenstein); University of West Virginia (A. Realini, J. Charlton, S. Zareparsi); Johns Hopkins University (D. Friedman); Stanford University (D. Vollrath, K. Singh), Eye Doctors of Washington (D. Gaasterland), Marshfield Clinic (Cathy McCarty). Hemin Chin serves as the NEI Staff Collaborator. This national collaborative study is supported by multiple NIH grants: NEI R01 EY015543 (Allingham); NEI U10 EY006827 (D. Gaasterland); NHLBI R01 HL073389 (E. Hauser); NEI R01 EY13315 (M. Hauser); NEI U10 EY009149 (Lichter); NEI R01 EY015473 (Pasquale); NEI U10 EY012118 (Pericak-Vance); NEI R03 EY015682 (Realini); NEI R01 EY011671 (Richards); NEI R01 EY09580 (Richards); NEI R01 EY013178 (Schuman); NEI R01 EY015872 (Wiggs); NEI R01 EY009847 (Wiggs); NEI R01 EY010886 (Wiggs); NEI R01 EY144428 (Zhang); NEI R01 EY144448 (Zhang); NEI R01 EY18660 (Zhang). Funding support for genotyping through exome sequencing, which was performed at the University of California, San Diego, was provided by the National Eye Institute (RC2 EY020678-01).

  Study phs000558

• MP2PRT: Comprehensive Genomic Profiling to Identify Alterations Associated with Relapse for NCI Standard Risk (SR) B-Lineage ALL and NCI High Risk (HR) B-Lineage ALL with Favorable Genetic Features

  The Molecular Profiling to Predict Response to Treatment (MP2PRT) program is part of the NCI's Cancer Moonshot Initiative. The aim of this program is the retrospective characterization and analysis of biospecimens collected from completed NCI-sponsored trials of the National Clinical Trials Network and the NCI Community Oncology Research Program. This study, titled "Comprehensive Genomic Profiling to Identify Alterations Associated with Relapse for NCI Standard Risk (SR) B-Lineage ALL and NCI High Risk (HR) B-Lineage ALL with Favorable Genetic Features," is one of the selected studies under this program. For this study, genomic characterization (WGS 30X, WXS, Total RNAseq) was performed on NCI Standard Risk B-lineage ALL patients who relapse and subsets of NCI High Risk B-lineage ALL patients who relapse as well as two non-relapse control cases for each relapse case. It was hypothesized that the comprehensive characterization of these sample sets will allow the identification of somatic genetic features that will facilitate early intervention to improve cure rates for those enrolled on future trials. Data were generated and genetic subtype was integrated with clinical variables, including age, presenting white blood cell count, sex, race, and levels of minimal residual disease at the end of induction. Additional secondary alterations were identified and included if they occurred in more than 10 patients. The study has been completed and a manuscript has been prepared.

  Study phs002005

• Developing Targeted Therapy for Patients with Multiple Myeloma and Gain or Amplification of Chr1q (1q+)

  Multiple myeloma (MM) frequently presents with gain or amplification of chr1q (1q+), which is associated with inferior response to treatment and poor outcomes. To develop targeted therapy for MM with 1q+, we leveraged external and in-house dependency screens and drug screens, along with single-cell sequencing of patient tumors with subclonal 1q+. We demonstrated that MM with 1q+ exhibits higher sensitivity to MCL1 and PI3K inhibitors, which may be synergistic and act through established and novel mechanisms. Two human MM cell lines with 1q+, KMS12BM and KMS11, were profiled with either single-cell RNA-sequencing (scRNA-seq) alone (KMS12BM, KMS11) or both scRNA-seq and whole-genome sequencing (WGS; KMS12BM) to understand the factors that determine response to MCL1 and PI3K inhibitors and how these inhibitors work.

  Study phs003886

• Characterization of genomic landscape of Peripheral T-cell Lymphomas, not otherwise specified (PTCL-NOS) (2018-10-30)

  Peripheral T-cell lymphomas not otherwise specified (PTCL-NOS) represent a heterogeneous group of nodal and extra-nodal mature T-cell lymphomas, with a low prevalence in Western countries. PTCL-NOSs account for about 25% of all PTCLs and are currently diagnosed based on exclusion criteria, as this lymphomas lack unifying morphological, phenotypic and genomic features. Cytogenetic and FISH analysis of PTCL-NOS samples have not revealed recurrent pathogenetic abnormalities, while gene expression profiling has shown only partial ability to segregate cases representing homogeneous clinic-pathological entities. This underscores the need to look at PTCL-NOS with innovative and high-throughput approaches to identify recurrent genetic lesions that could further our understanding of the biology of this heterogeneous group of diseases, provide better diagnostic tools and perhaps new targets for innovative treatments. Our aim is to study ~15 patients affected by PTCL-NOS. Out study will be funded by a private, non-profit Italian cancer research fund (Associazione Italiana per la Ricerca sul Cancro, www.airc.it) based on a grant owned by Anna Dodero and Cristiana Carniti, hematologists at INT. Samples will be analysed by whole genome sequencing using Illumina X10 machines, on a 150bp-PE protocol. Data will be analysed using the pipeline available in Team 78, under the supervision of Peter Campbell, the WTSI faculty who will oversee the project, and by Francesco Maura, visiting scientist at the WTSI. . This dataset contains all the data available for this study on 2018-10-30.

  Dataset EGAD00001004428

• Intraductal transplantation models of human pancreatic ductal adenocarcinoma reveal progressive transition of molecular subtypes

  Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common malignancy, with little improvement in patient outcomes over the past few decades. Recently, subtypes of pancreatic cancer with different prognoses have been elaborated. However, the inability to model these subtypes has precluded mechanistic investigation of their origins. Here, we present an orthotopic xenotransplantation model of human patient-derived PDAC organoids in which organoids are grafted via direct injection into the pancreatic duct of immunocompromised (NSG) mice. Tumors that arise from these intraductally grafted organoids (IGOs) enable the distinction of the two main PDAC subtypes: intraepithelial neoplasms from this model progress in an indolent or invasive manner representing the classical or basal-like subtypes of PDAC, respectively, depending on which organoid they originate from. RNA-sequencing was used to characterize the tumors that resulted from IGO xenografts, and to compare the fast- and slow-progressing IGO tumors. Tumors generated using a traditional orthotopic xenograft model, in which organoids are injected into the parenchyma of the pancreas (i.e. orthotopically grafted organoids, or OGOs), were also sequenced for comparison with the IGO tumors. To further characterize the model, laser-capture microdissection followed by RNA-sequencing was used to compare intraductal to invasive lesions resulting from IGOs. To better understand the connection between KRAS signaling and the fast-progressing phenotype, RNA-sequencing was used to compare cultured organoids in which oncogenic KRAS (GeneID: 3845) was hyperactivated to control organoids, and to compare laser-capture microdissected lesions derived from IGOs of KRAS-hyperactivated organoids to lesions derived from control organoids. To ascertain copy number, low-coverage, whole genome DNA-sequencing was performed on organoids cultured in vitro, and on laser-capture microdissected lesions derived from IGO tumors.

  Study phs002045

• Ultra-Fast Patient-Derived Xenografts Identify Functional and Spatial Tumour Heterogeneities that Drive Therapeutic Resistance

  Treatment of patients with advanced cancers increasingly relies on agents targeting specific molecular or cellular aberrations. These expensive therapies often fail because of pre-existing drug resistance. Intra-tumoural molecular and micro-environmental heterogeneity resistance can create resistance in one or more subclones of a tumour, leading to spatio-functional heterogeneity. We created a rapid approach for quantifying tumour functional phenotypes based on tumour-implantation into the chorioallantoic membrane of chick embryos. We apply this technique to 43 separate biopsies from 6 patients with renal cell carcinoma (RCC) with 36 replicates per biopsy, achieving a 93.6% engraftment rate (1449/1548). Challenging these models with sunitinib, an anti-angiogenic therapy frequently used in RCC allowed us to quantify spatio-functional heterogeneity in individual patients. Prediction of de novo drug resistance in advanced cancer patients would facilitate precision medicine by tailoring systemic therapies and improve clinical trial design outcome measures. We describe a patient-derived xenograft platform where fresh patient tumour samples are implanted into the chorioallantoic membrane (CAM) of chick embryos at high engraftment efficiencies, permitting large scale “tumour avatar” studies to guide the selection of drugs and to predict clinical drug resistance outcomes in renal cell carcinoma (RCC) patients. Applying this “tumour avatar” model in a co-clinical trial on RCC patients, we observe intra-tumoural functional heterogeneity with sunitinib treatment, revealing the presence of drug-resistant clones prior to the initiation of therapy. Multi-regional exome Matched DNA sequencing of the primary tumour and metastases revealed DNA mutational signatures associated with sunitinib resistance at baseline and after treatment. These These studies demonstrate a rapid and affordable method of findings confirm the existence of genetic and surveying functional tumour heterogeneities heterogeneity.

  Study EGAS00001002627

• Characterization of DLBCL with a PMBL gene expression signature

  Primary mediastinal large B-cell lymphoma (PMBL) is a type of aggressive B-cell lymphoma that typicallyaffects young adults, characterized by presence of a bulky anterior mediastinal mass. Lymphomas withgene expression features of PMBL have been described in non-mediastinal sites, raising questions abouthow these tumors should be classified.Here, we investigated whether these "non-mediastinal PMBLs" are indeed PMBLs or instead represent adistinct group within DLBCL. From a cohort of 325 de novo DLBCL cases, we identified tumors frompatients without evidence of anterior mediastinal involvement that expressed a PMBL expression signature(nm-PMBLsig-pos, n=16, 5%). The majority of these tumors expressed MAL and CD23 – proteins typicallyobserved in bona fide PMBL (bf-PMBL). Evaluation of clinical features of nm-PMBLsig-pos cases revealedclose associations with DLBCL, and the majority displayed a germinal center B-cell-like cell-of-origin(GCB). In contrast to bf-PMBL, nm-PMBLsig-pos patients presented at an older age, did not show pleuraldisease, and bone/bone marrow involvement was observed in three cases. However, while clinicallydistinct from bf-PMBL, nm-PMBL-sig-pos tumors resembled bf-PMBL at the molecular level with upregulationof immune response, JAK-STAT, and NF-kB signatures. Mutational analysis revealed frequent somatic genemutations in SOCS1, IL4R, ITPKB and STAT6, as well as CD83 and BIRC3, with the latter genes beingsignificantly more frequently affected than in GCB-DLBCL and bf-PMBL.Our data establish nm-PMBLsig-pos lymphomas as a group of DLBCL with distinct phenotypic and geneticfeatures, and potential implications for gene expression- and mutation-based subtyping of aggressive Bcell lymphoma and related targeted therapies.

  Study EGAS00001005057

• Data Use Ontology (DUO)

  Data Use Ontology Data Use Ontology at EGA The EGA is committed to its involvement in the work of GA4GH. In an effort to enhance data discoverability and streamline data access, EGA have implemented the use of the Data Use Ontology (DUO), based on consent codes as described in Dyke et al. 2017. The Data Use Ontology codes will be displayed on the live dataset page of your submission to advise any would be requestor on how the data can be used and also to enhance data discoverability as users will be able to search on these codes to find applicable datasets. DUO can be browsed online via the Ontology Lookup Service Learn more reading the Data Use Ontology publication and the GA4GH Machine-Readable Consent Guidance! Check our DAC Portal Take The Tour and learn how to add DUO codes to your policy! Term Shorthand Label Description DUO:0000004 NRES no restriction This data use permission indicates there is no restriction on use. DUO:0000042 GRU general research use This data use permission indicates that use is allowed for general research use for any research purpose. DUO:0000006 HMB health or medical or biomedical research This data use permission indicates that use is allowed for health/medical/biomedical purposes; does not include the study of population origins or ancestry. DUO:0000007 DS disease specific research This data use permission indicates that use is allowed provided it is related to the specified disease. DUO:0000011 POA population origins or ancestry research only This data use permission indicates that use of the data is limited to the study of population origins or ancestry. DUO:0000012 RS research specific restrictions This data use modifier indicates that use is limited to studies of a certain research type. DUO:0000015 NMDS no general methods research This data use modifier indicates that use does not allow methods development research (e.g., development of software or algorithms). DUO:0000016 GSO genetic studies only This data use modifier indicates that use is limited to genetic studies only (i.e., studies that include genotype research alone or both genotype and phenotype research, but not phenotype research exclusively) DUO:0000018 NPUNCU not for profit, non commercial use only This data use modifier indicates that use of the data is limited to not-for-profit organizations and not-for-profit use, non-commercial use. DUO:0000019 PUB publication required This data use modifier indicates that requestor agrees to make results of studies using the data available to the larger scientific community. DUO:0000020 COL collaboration required This data use modifier indicates that the requestor must agree to collaboration with the primary study investigator(s). DUO:0000021 IRB ethics approval required This data use modifier indicates that the requestor must provide documentation of local IRB/ERB approval. DUO:0000022 GS geographical restriction This data use modifier indicates that use is limited to within a specific geographic region. DUO:0000024 MOR publication moratorium This data use modifier indicates that requestor agrees not to publish results of studies until a specific date. DUO:0000025 TS time limit on use This data use modifier indicates that use is approved for a specific number of months. DUO:0000026 US user specific restriction This data use modifier indicates that use is limited to use by approved users. DUO:0000027 PS project specific restriction This data use modifier indicates that use is limited to use within an approved project. DUO:0000028 IS institution specific restriction This data use modifier indicates that use is limited to use within an approved institution. DUO:0000029 RTN return to database or resource This data use modifier indicates that the requestor must return derived/enriched data to the database/resource. DUO:0000043 CC clinical care use This data use modifier indicates that use is allowed for clinical use and care. DUO:0000044 NPOA population origins or ancestry research prohibited This data use modifier indicates use for purposes of population, origin, or ancestry research is prohibited. DUO:0000045 NPU not for profit organisation use only This data use modifier indicates that use of the data is limited to not-for-profit organisations. DUO:0000046 NCU non-commercial use only This data use modifier indicates that use of the data is limited to not-for-profit use. Point to Notice: For the consent code DUO:0000007 where data is restricted to use on a specific disease, please accompany it with an appropriate ontology from MONDO e.g., If the data is restricted to the use of research into juvenile idiopathic arthritis the code should be displayed as DUO:0000007; MONDO:0011429.

  Documentation access/data-access-committee/data-use-ontology

• Towards a Genomic Understanding of Myeloma

  This project was designed to describe genetic abnormalities in primary samples from patients with multiple myeloma by next generation sequencing. We generated sequence data from multiple myeloma (MM) patients analyzing DNA both from tumor cells (purified from bone marrow using CD138 selection as a marker of plasma cells) and from normal peripheral blood cells (either whole blood or Ficoll-purified mononuclear cells). Using massively parallel sequencing technology (Illumina GA-2 or HiSeq)), we performed whole-genome sequencing (WGS) and/or whole-exome sequencing (WES). The initial set currently deposited contains data from 38 MM patients (23 patients surveyed by WGS and 16 patients by WES, with one patient analyzed by both approaches). Genomes were sampled to high depth, obtaining an average of 33X coverage and 104X coverage for WGS and WES tumors, respectively. The normal samples had similar coverage. Our goal is to help researchers understand the complex genetic landscape of multiple myeloma and provide a resource for the generation of biological hypotheses.

  Study phs000348

• Genome-Wide Association Study of Parkinson Disease: Genes and Environment

  This is a gene-environment study of Parkinson's disease. PD is a common, progressive, age-related, movement disorder that affects 1-2% of the people over the age of 65. The NeuroGenetics Research Consortium (NGRC) is the infrastructure of the study. Protocols and methods are standardized across NGRC clinics and labs as much as possible. The 2000 patients and 2000 control subjects selected for this GWAS were recruited at the NGRC-affiliated movement disorder clinics in Oregon, Washington, Georgia and New York. All 4000 subjects were white and all DNA samples were extracted from whole blood and unamplified. Seventy-five percent of subjects have data on cigarette smoking and caffeinated coffee consumption, which are inversely associated with PD risk. This study population represents the norm for clinical genetic studies of PD; i.e., NGRC estimates of risk to relatives, heritability, genotype frequencies, and exposure frequencies (see references) are very close to estimates from meta-analyses.

  Study phs000196

• Type I Interferon Exacerbates Mycobacterium Tuberculosis Induced Human Macrophage Death

  In this study, we tested whether type I interferons (IFN-I), namely IFN-alpha and IFN-beta, may promote Mycobacterium tuberculosis (Mtb) pathogenesis by exacerbating cell death of human monocyte-derived macrophages (MDM) infected with Mtb. We differentiated the MDM under two different published methods (see Document Method.pdf for Table 1 of Methods). To determine if MDM infected with Mtb upregulates IFN-I transcripts, signaling factors, or IFN-I stimulated genes (ISGs), the MDM were infected with Mtb or treated with an activator of stimulator of IFN genes (STING), diamidobenzimidazole (di-ABZI). STING activation acted as a positive control for IFN-I induction and ISG upregulation. Indeed, di-ABZI treated MDM differentiated under both methods upregulated ISGs 24 hpi. At 24 hour post treatment, MDM differentiated under one method, but not under another method, upregulated ISGs, such as ISG15, IFITM3, and CXCL10, upon Mtb infection. MDM differentiated under both methods upregulated ISGs upon di-ABZI treatment.

  Study phs003607

• Genomic Profiling of Melanoma

  This study reports on genomic profiling [whole-exome sequencing (WXS), bulk RNA sequencing (RNA-seq), and/or single-cell RNA sequencing (scRNA-seq)] of patient-derived melanoma samples and matched normal samples. The goal is to elucidate the genetic and cellular basis of sun-exposed and sun-shielded melanomas and to relate these findings to survival and regional metastasis. Specimens were collected by the Tissue Resource Core of the Yale SPORE in Skin Cancer with participants' informed signed consent according to Health Insurance Portability and Accountability Act (HIPAA) regulations with a Human Investigative Committee protocol. The melanomas used for sequencing were from fresh or snap-frozen tumors, or from short-term cell cultures. The cell cultures were routinely checked for mycoplasma contamination and were discarded when found positive. Matching normal DNA was from circulating lymphocytes or normal skin. We also include 77 WES-sequenced samples from the Yale Spitzoid neoplasm repository, which collects specimen and data according to a protocol approved by the Yale Human Investigative Committee.

  Study phs000933

• Genomic Landscape of Apical Periodontitis

  We undertook the first genome-wide association (GWAS) study of apical periodontitis, enrolling 932 patients with deep carious lesions at UTHealth School of Dentistry and the University of Pittsburgh School of Dental Medicine. We used a case-control design to compare those with apical periodontitis to those without. Genotype data was generated for all participants and imputed using the TOPMed reference panel. We performed a single-variant association testing, a subphenotype analysis, and a genetically regulated expression association analysis, and generated a polygenic risk score and performed phenome-wide association analysis. We identified eight near-genome-wide significant loci for our primary outcome, eight genes where genetically regulated expression was associated with apical periodontitis status, and 33 phecodes that were associated with the generated polygenic risk score. We also replicated three loci previously reported in the literature. Genotype, phenotype, and results from the primary association analysis will be available via dbGaP.

  Study phs003252

• Uterine_Atlas_Endometriosis

  Uterine Atlas Endometriosis Endometriosis is a chronic inflammatory disease driven by oestrogen, affecting around 10% of women of child-bearing again world-wide. It is described by the presence of endometrium-like tissue outside of the uterus (ectopic endometriosis tissue) and debilitating chronic pain. There is a lack of understanding of endometriosis pathogenesis, as well as cellular composition of both the eutopic endometrium and ectopic endometriosis tissue of endometriosis patients.There are therefore two main aims for this study. Using single cell genomics and spatial methods we aim to: I) characterise endometrial cellular census in women with and without endometriosis II) characterise cellular census of ectopic endometriosis tissue Furthermore, we aim to establish endometrial organoids and endometriosis organoids from the samples collected and characterise these using single cell genomics and spatial methods. 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 EGAS00001004725

• New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

  Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated “CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)”, “CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)”, “CNS high grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)”, and “CNS high grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)”, will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

  Study EGAS00001001632

• 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