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• CRISPR iPSC methods paper

  This submission is of the sequencing data used in the CRISPR iPSC methods paper. Specifically it is 3 fastq files that each represent a replicate of an experiment to transduce the Toronto KnockOut CRISPR Library - Version 3 (TKOv3) into inferred pluripotent stem cell (iPSC) derived macrophages. The sequencing is of the guide RNAs from the TKOv3 having been extracted from the transduced iPSC derived macrophages.

  Dataset EGAD00001007020

• scRNA-seq of HSPC treated with gemcitabine and carbplatin

  The study used cryopreserved hematopoietic stem and progenitor cells (HSPCs) harvested from one patient with chronic myelogenous leukemia (CML). The cells were thawed and acclimatized for 48 hours in StemMACS HSC Expansion Media XF (Miltenyi Biotec) supplemented with StemMACS HSC Expansion Cocktail (Miltenyi Biotec) at 37°C in a humidified atmosphere containing 5% CO2. 4 samples of 2000000 HSPCs in 2 ml media each were then prepared and treated for 24 hours: carboplatin-high: 150 µg/ml carboplatin carboplatin-low: 18.75 µg/ml carboplatin gemcitabine: 25 ng/ml gemcitabine control: no drug Single-cells were subsequently extracted using the ddSEQ™ Single-Cell Isolator (Bio-Rad) and later sequenced using the SureCell™ Whole Transcriptome Analysis 3' Library Prep Kit (Illumina) on the NextSeq 500 System (Illumina) using the NextSeq 500/550 High Output Kit v2.5 150 Cycles (Illumina) all following the manufacturer's instructions. FASTQ-files were then processed following the ddSeeker (Romagnoli, D., et al., BMC Genomics 2018, doi:10.1186/s12864-018-5249-x) and Drop-seq (Macosko, E.Z., et al., Cell 2015, doi:10.1016/j.cell.2015.05.002) protocols for processing scRNA-seq data to yield the final digital gene expression for each cell.

  Study EGAS00001004381

• METABRIC

  Solid tumors are complex tissues composed of a mixture of cancer and normal cells, which complicates the interpretation of their molecular profiles. Normal cell contamination can dilute cancer cell information and tissue architecture is generally not reflected in molecular assays. To address these challenges, we developed a computational approach based on standard Haematoxylin and Eosin-stained sections and demonstrated its power in a discovery cohort of 323 breast tumors and an independent validation cohort of 241 tumors. First, to deconvolute cellular heterogeneity and detect subtle genomic aberrations, we introduced an algorithm based on tumor cellularity to increase the comparability of copy-number profiles between samples. Second, we demonstrated that a predictor for survival integrating image-based and molecular features significantly outperforms classifiers based on single data types. Third, we described and validated a novel, independent prognostic factor based on quantitative analysis of spatial patterns between stromal cells, which are not detectable by molecular assays. Our quantitative methods refine and complement molecular assays of tumor samples and could benefit all large-scale cancer studies.First, to deconvolute cellular heterogeneity and detect subtle genomic aberrations, we introduced an algorithm based on tumor cellularity to increase the comparability of copy-number profiles between samples. Second, we demonstrated that a predictor for survival integrating image-based and molecular features significantly outperforms classifiers based on single data types. Third, we described and validated a novel, independent prognostic factor based on quantitative analysis of spatial patterns between stromal cells, which are not detectable by molecular assays. Our quantitative methods refine and complement molecular assays of tumor samples and could benefit all large-scale cancer studies.

  Study EGAS00000000098

• Genomic analysis of HPV positive versus HPV negative esophageal adenocarcinoma

  High-risk human papillomavirus (hr-HPV) has been implicated in a subset of patients with esophageal adenocarcinoma (EAC). We therefore hypothesized that HPV associated EAC may have distinct genomic aberrations compared with viral negative esophageal cancer as shown in Head and Neck cancer and cervical cancer. Whole exome sequencing (WES) was performed to explore the mutational landscape and potential molecular signature of HPV positive versus HPV negative EAC, which includes four hr-HPV-positive and 8 HPV-negative treatment naive fresh-frozen EAC tissue specimens and matched normal tissues.

  Study EGAS00001001340

• Lung_Multi_site_Targeted_Sequence_Capture

  DNA extracted from multiple biopsies taken from different areas of primary lung tumours will be subjected to targeted re-sequencing and analysed in order to assess intra-tumour heterogeneity with respect to mutations in a selection of cancer related genes.

  Study EGAS00001000436

• Multisite_Primary_Breast_Cancer

  DNA extracted from multiple biopsies taken from different areas of primary breast tumours will be subjected to targeted re-sequencing and analysed in order to assess intra-tumour heterogeneity with respect to mutations in a selection of cancer related genes.

  Study EGAS00001000891

• Single Cell and Tissue Level Functional Genomics Analysis of Astrocyte-Related Mechanisms in Taupathy

  This data is the first part of a larger single cell and tissue level functional genomics analysis of dementias with tau pathology.  Cellular resolution will clarify the role of glial genes and pathways in neurodegenerative disease. This includes understanding the role of microglia and astrocytes in neurodegenerative disorders characterized by Tau protein pathology. To achieve a refined view of microglial neuroinflammatory signaling in tau-associated neurodegeneration, we performed a functional genomic analysis that integrated time-course gene expression data from mouse models expressing human mutant MAPT (the tau gene) with single nuclear sequencing data obtained from patients with frontotemporal dementia with Tau protein pathology (Pick’s disease). This included microglia-specific gene expression data obtained from single nuclear sequencing of postmortem frozen precentral gyrus samples collected from 16 total individuals, including 8 subjects with clinical diagnosis of behavior variant frontotemporal dementia and neuropathological diagnosis of Pick’s disease (Tau protein pathology) and controls (n=8). Our findings present detailed molecular profiles of disease-associated microglial transitions over the course of tau-associated neurodegeneration. Furthermore, we demonstrate overlap between microglia profiles obtained from precentral gyrus of patients with Pick’s disease with those up-regulated during the neurodegenerative stage in mice expressing human MAPT mutations.

  Study phs002197

• Deep targeted DNA sequencing dataset for the study "Molecular characteristics in Burkitt lymphoma over age groups"

  We performed deep targeted DNA sequencing with a panel of 134 selected cancer-related genes previously identified to be recurrently mutated in BL/B-AL. A Nextera rapid capture custom kit was designed using the Illumina DesignStudio. For every gene, all regions in which previous mutations had been described were covered. For 40 of these genes, the entire coding sequence was covered. Targeted deep sequencing was performed on a MiSeq-Sequencer using MiSeq Reagent Kit v2 (300 cycle) with 24 samples per run. There are 396 samples in this targetedDNAseq-dataset with 298 tumors (288 patients and 10 cell lines) and 98 normals. There are 132 female, 262 male, and 2 unknown gender samples in this dataset.

  Dataset EGAD00001007708

• 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

• Chromosomal copy number heterogeneity predicts survival rates across cancers

  Survival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis1,2. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing3. Here, we introduce a scalable measure of chromosomal copy number heterogeneity that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 35 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.

  Study EGAS00001004702

• 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

• NCI CCSG CCDI Supplement Additional Genomic Submission

  The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. This supplement data from the Beat AML program provides Adolescent and Young Adult (AYA) and pediatric tumor specimens not previously released. These data include exome and RNA level characterization as well as analyses of ex vivo drug sensitivity. Collectively, this data can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of leukemia in pediatric and AYA populations.

  Study phs002599

• RNA sequencing of circulating human immune cells before and after interleukin-2 immunotherapy in systemic lupus erythematosus patients

  Within the investigator-initiated clinical trial Charact-IL-2 (ClinicalTrials.gov Identifier: NCT03312335), we treated 12 female systemic lupus erythematosus patients with low-dose interleukin-2. Patients received 4 cycles of 5 daily injections of 1.5 million international units interleukin-2 over 9 weeks. This study aimed at investigating interleukin-2-induced transcriptional changes in circulating human immune cells, and to define changes in T cell receptor clonality before and after interleukin-2 immunotherapy. For this purpose, blood was collected from patients before and after each treatment cycle.

  Study EGAS50000000458

• Summarized somatic variant calls from CMMRD-associated high-grade gliomas

  This dataset contains summarized somatic variant call data derived from paired tumor–blood whole-exome sequencing of human samples. Access to the dataset is controlled and granted only upon submission and approval of a formal data access request. Requests are reviewed by the Data Access Committee led by the Principal Investigator to ensure compliance with applicable legal, ethical, and data protection requirements. Users must not attempt to re-identify study participants and must comply with all relevant confidentiality and data protection regulations. In accordance with local legal and ethical requirements, individual-level raw sequencing data are not shared.

  Dataset EGAD50000002180

• Long-read RNA-seq of doxycycline-inducible DUX4 human myoblast cell lines

  The dataset includes the PacBio full-length isoform sequencing data of DUX4i myoblasts (Clone-5) with and without 16-hour DOX-treatment (referred to as DUX4- and DUX4+; n=1 in each condition).

  Dataset EGAD50000000718

• Chromatin Profiling in Twins (2019-08-21)

  50 lymphoblastoid cell lines of adult female Twins which are part of the MuTHER study, subjected to Chromatin Immunoprecipitation using an antibody for H3K4me1. H3K4me1 peaks mark distal regulatory elements. . This dataset contains all the data available for this study on 2019-08-21.

  Dataset EGAD00001005274

• IBDCA_Edinburgh

  In this experiment we have sequenced tumour normal pairs from patients presenting with CRC who have a prior history of inflammatory bowel disease. The idea is to identify driver mutations, new genes and novel pathways associated with the development of these malignancies.

  Dataset EGAD00001001330

• Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma.

  We used targeted sequencing to capture and measure the abundance as well as the size profiles of EBV DNA in plasma of subjects with and without NPC

  Dataset EGAD00001004204

• Perturb-seq dataset

  We performed a systematic, genome-wide investigation of enhancer regions in colorectal cancer (CRC). We identified 12,117 putative enhancer regions using H3K27ac and H3Kme1 ChIP-seq and ATAC-seq. We performed scRNA-seq in HT29 and SW480 (MSS CRC cell lines) using the Parse Biosciences WT-mega kit with CRISPRi/dCas9 inhibition of these regions (Perturb-seq). The Parse split-pipe pipeline was used to demultiplex the raw fastq files into the processed files (mtx files for genes and gRNA) for each cell line.

  Dataset EGAD50000000375

• scRNAseq of ALS patients

  The data set contains information from 9 individuals (5 ALS + 4 controls) using single cell RNA sequencing in combination with TCR V(D)J sequencing to study the immune profile of the central nervous compartment (CSF). Sequencing was done using 10x Genomics platform (5’ scRNAseq & V(D)J Reagent Kits v1.1). 5P and TCR libraries were then pooled and for sequencing on the NovaSeq sequencer. Provided files are in .fastq.gz format and per individual four files are available (Read 1&2 and Lane 1&2).

  Dataset EGAD00001009623

• RNA-seq analysis of CCO+/CCO- hepatocytes in normal human liver

  RNAseq data from Passman et al 2023. Clonal CCO-deficient hepatocyte patches and nearby CCO-proficient hepatocytes were identified in morphologically normal human livers and sampled at varying distances along the PT-CV axis. Samples are characterised according to their location within the liver lobule, with "PT" denoting samples abutting the portal triad, "CV" denoting samples abutting the central hepatic vein, and "Mid" sampled acquired midway between these structures. Analysis was performed on an Illumina Nextseq using a high output kit and 100 single-end cycles.

  Dataset EGAD00001010033

• Risk alleles of membranous nephropathy and recurrence of the disease on the grafted kidney

  Samples are from patients enrolled in an international multicentric study aimed to define the genetic determinants of recurrence of membranous nephropathy in the kidney graft. They include 248 samples from patients with MN including 105 patients who received a graft, their 105 graft donors, and 192 controls all of Caucasian origin. Files from targeted-capture of HLA and PLA2R loci are available as fastq files.

  Dataset EGAD00001007831

• Tumour gene expression signature in primary melanoma predicts long-term outcomes: A prospective multicentre study

  Adjuvant systemic therapies are now routinely used following resection of stage III melanoma, however accurate prognostic information is needed to better stratify patients. We used differential expression analyses of primary tumours from 204 RNA-sequenced melanomas within a large adjuvant trial, identifying a 121 metastasis-associated gene signature. This signature strongly associated with progression-free (HR=1.63, p=5.24x10-5) and overall survival (HR=1.61, p=1.67x10-4), and validated in 177 regional lymph nodes metastasis as well as two externally ascertained datasets. The machine learning classification models trained using the signature genes performed significantly better in predicting metastases than models trained with clinical covariates (pAUROC=0.02), or published prognostic signatures. The signature score negatively correlated with measures of immune cell infiltration (ρ=-0.75, p<2.2x10-16), with a higher score representing reduced lymphocyte infiltration and a higher 5-year risk of death in stage II melanoma. Our expression signature identifies melanoma patients at higher risk of metastases and warrants further evaluation in adjuvant clinical trials.

  Study EGAS00001004664

• Expression-Based Subtypes Define Pathologic Response to Neoadjuvant Immune-Checkpoint Inhibitors in Muscle-Invasive Bladder Cancer

  Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling.

  Study EGAS00001005549

• ATAC-seq dataset of Single cell RNA sequencing reveals induced bifurcated differentiation after RUNX1::RUNX1T1 depletion in patient-derived leukemic blasts

  In this study, we demonstrate that primary AML cells harboring the chromosomal translocation t(8;21) are critically dependent on the corresponding fusion gene, RUNX1::RUNX1T1, to suppress differentiation and maintain stemness. Silencing RUNX1::RUNX1T1 expression using siRNA-loaded lipid nanoparticles induces significant changes in chromatin accessibility, redirecting the leukemia-associated transcriptional network towards a myeloid differentiation program. Single-cell analyses reveal that this transcriptional reprogramming is associated with the depletion of immature stem and progenitor-like cell populations, accompanied by an expansion of granulocytic and eosinophilic/mast cell-like populations with impaired self-renewal capacity.

  Dataset EGAD00001015509

• scRNA-seq dataset of Single cell RNA sequencing reveals induced bifurcated differentiation after RUNX1::RUNX1T1 depletion in patient-derived leukemic blasts

  In this study, we demonstrate that primary AML cells harboring the chromosomal translocation t(8;21) are critically dependent on the corresponding fusion gene, RUNX1::RUNX1T1, to suppress differentiation and maintain stemness. Silencing RUNX1::RUNX1T1 expression using siRNA-loaded lipid nanoparticles induces significant changes in chromatin accessibility, redirecting the leukemia-associated transcriptional network towards a myeloid differentiation program. Single-cell analyses reveal that this transcriptional reprogramming is associated with the depletion of immature stem and progenitor-like cell populations, accompanied by an expansion of granulocytic and eosinophilic/mast cell-like populations with impaired self-renewal capacity.

  Dataset EGAD00001015510

• Germline and somatic variants in myelodysplastic syndrome and therapy-related myeloid neoplasms

  Somatic mutation frequencies in patients with therapy-related myeloid neoplasms (129 patients, 181 samples including bone marrow, mesenchymal stromal cells and hair DNA) and primary myelodysplastic syndrome (108 patients, 215 samples including bone marrow, mesenchymal stromal cells and hair DNA) is assessed by deep sequencing of selected genes, using a Fluidigm Access Array, a Nimblegen capture panel and an Ion AmpliSeq panel. The dataset consists of paired fastq files obtained by either Hiseq (2x101bp) or Nextseq (2x150bp) Illumina sequencing. The mutational burden is found to be similar in both, however the distribution of variants is different. Correlation of the mutational spectrum with prognosis is also observed.

  Dataset EGAD00001004861

• DNA repair in BLM deficient hiPSCs

  We are aiming to investigate repair of a double strand break (DSB) within the genome in the presence and absence of the BLOOM protein. Zinc Finger Nucleases introduce DSBs at specified loci within the genome. Using sequencing we will assess the size of the deletion following repair. Protocol 1. Transfect normal and BLOOM deficient human iPS cells with ZFNs, using AMXA 2. Harvest cells after 5 days 3. Perform column extraction of DNA 4. PCR-amplify the ZFN region 5. Sequence and analyse repair of the DSB This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001000819

• A comprehensive DNA methylation landscape of human and mouse cell lines derived from hematological malignancies

  The dataset from Infinium Human MethylationEPIC v1.0 (IDAT files) includes 91 primary samples from patients with B-cell acute lymphoblastic leukemia (B-ALL) (n=34) and T-cell acute lymphoblastic leukemia (T-ALL) (n=57). This dataset was used in the article "A Comprehensive DNA Methylation Landscape of Human and Mouse Cell Lines Derived from Hematological Malignancies" to validate differentially methylated CpG sites, which were utilized to classify hematologic malignancies.

  Dataset EGAD50000000888

• RNA-seq data from primary AML samples with t(3;8)

  RNA-seq was generated to investigate differences in gene expression between t(3;8) AML and other primary AMLs. Briefly, sample libraries were prepared using 500 ng of input RNA according to the KAPA RNA HyperPrep Kit with RiboErase (HMR) (Roche) using Unique Dual Index adapters (Integrated DNA Technologies, Inc.). Amplified sample libraries were paired-end sequenced (2x100 bp) on the Novaseq 6000 platform (Illumina

  Dataset EGAD00001006819

• Multi-region sequencing of 10 neuroblastoma cases

  To investigate intratumour heterogeneity and to better understand tumour evolution in neuroblastoma, we have performed a multi-region whole-exome sequencing on a total of 51 spatially separated tumor samples from 9 primary neuroblastomas (2 low-risk, 1 intermediate-risk and 6 high-risk) and 1 relapsed neuroblastoma. We also assessed the impact of chemotherapy on the clonal expansion by sequencing tumour regions from one medium risk and one high-risk tumour for which we had matched samples obtained at diagnosis and after chemotherapy.

  Dataset EGAD00001008020

• A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours

  We generated a single-cell RNA-seq atlas capturing over 100,000 cells spanning all stages of the mouse cerebral development. By examining data from over 100 cerebral tumour samples, our study reveals that, despite the phenotypic/genotypic differences between the tumour types, they are all comprised of developmental sublineages that map most closely to embryonic or juvenile stages of development.

  Study EGAS00001006237

• Access to public datasets in the EGA

  Dac EGAC00001000514

• CHEWIE ctDNA in Rhabdomyosarcoma

  Targeted DNA based panel of multiple ctDNA samples from 10 patients througout clinical care to assess treatment response. The panel is custom-designed and property of UGS, IC.

  Dataset EGAD00001011127

• SUM-seq data for Macrophage polarisation to M1 and M2 phenotypes experiment

  We stimulated iPSC-derived M0 macrophages with LPS and IFN-γ to induce M1 polarization or IL-4 to induce M2 polarization. To discern early and sustained responses at chromatin accessibility and gene expression levels, we collected samples at five time points along the two polarization trajectories; prior to stimulation (M0) and at 1-hour, 6-hour, 10-hour, and 24-hour intervals, each sampled in duplicates totaling 18 samples, and subjected them to SUM-seq library preparation. Sequenced files for both data modalities are provided as demultiplexed fastq files.

  Dataset EGAD50000001206

• Integrated single cell analysis in transformed follicular lymphoma

  Histological transformation of follicular lymphoma to aggressive form occurs 2-3% per year with poor outcome. Divergent evolution and an altered tumour-microenvironment (TME) have been implicated during transformation. However, phenotypic consequences of this evolution and its implication in TME remain unknown. To address this, we performed single cell whole genome and whole transcriptome sequencing of paired pre/post transformation patient samples. We further performed scWTS of additional samples from patients without transformation. Our analysis revealed evolutionary dynamics of transformation at unprecedented resolution. Integration of scWGS and scWTS identified pathways upregulated during evolution. scWTS analysis revealed a shifting TME landscape, with an exhausted signature emerging during transformation. Using multi-color immunofluorescence we transferred these findings to a TME-based transformation biomarker, subsequently validated in independent pretreatment cohorts. Taken together, our results provide a comprehensive view of the combined genomic and phenotypic evolution of malignant cells during transformation, and shifting cross-talk between malignant cells and TME.

  Study EGAS00001007023

• NGS sequencing data of archival FFPE tumor tissue

  The aim of the study was to identify mutations in key ovarian cancer genes (BRCA1, BRCA2,TP53, PTEN, ATM, ATR, NF1) in archival fresh-frozen paraffin embedded (FFPE) tumor tissue from platinum-resistant ovarian cancer patients enrolled in the phase I/II GANNET53 clinical trial. From the enrolled 133 patients, archival FFPE tissue was available and DNA was extracted thereof. The DNA samples passing quality control (n=118) were NGS sequenced using the SureSeq™ Ovarian Cancer Panel and the NGS Library Preparation kit (Oxford Gene Technology), which covers all exons of 7 key ovarian cancer genes for single nucleotide variants (SNV) and indels, and the Illumina MiSeq platform. For the paired-end runs, one Read 1 (R1) and one Read 2 (R2) FASTQ file were created for each sample. FASTQ files were compressed and created with the extension \.fastq.gz.

  Dataset EGAD50000001371

• Broad utility of ultrasensitive analysis of circulating tumor DNA (ctDNA) dynamics across solid tumors treated with immunotherapy

  Here, we applied a whole-genome, tumor-informed approach to study ctDNA in more than 202 advanced-stage cancer patients treated at VHIO. This study demonstrates the efficacy of ultrasensitive ctDNA as a broad biomarker in a large pan-cancer discovery and validation cohort, spanning 24 tumor types treated with diverse immunotherapy modalities. It demonstrates ctDNA’s potential for early response assessment, survival prediction, and distinguishing true progression from pseudoprogression, enhancing its clinical relevance. This dataset captures the plasma sequencing data from the project.

  Dataset EGAD50000001813

• Pre-neoplastic somatic mutations including MYD88L265P in lymphoplasmacytic lymphoma

  In this study, we sequenced multiple stages of the B-lineage in elderly individuals and patients with lymphoplasmacytic lymphoma to study whether mutations are accumulated in normal-cell counterparts prior to lymphoma

  Dataset EGAD00001008196

• Novel de novo pathogenic variant in the GNAI1 as a cause of severe disorders of intellectual development with autistic features

  Our probands A and B are boys-monozygotic twins with the clinical diagnosis of severe intellectual impairment, developmental stagnation, and dysphasia. They were diagnosed at the Department of Medical Genetics and Genomics (University Hospital Brno). Parents provided written informed consent, which was approved by the Research Ethics Committee of Masaryk University and Ethics Committee of University Hospital Brno. Peripheral blood samples were collected in sterile heparinized tubes for cytogenetic analysis. Genomic DNA samples were obtained from 1 ml peripheral blood in EDTA, according to the standard DNA isolation process using the MagNaPure system (Roche Diagnostics, Basel, Switzerland). Quality and quantity were checked using a DeNovix DS-11 Spectrophotometer (DeNovix Inc., Wilmington, DE, USA) and Qubit® 2.0 (Thermo Fisher Scientific, Inc., Waltham, MA, USA).

  Dataset EGAD00001007736

• Whole exome sequencing on primary retinoblastoma tissues and matching lymphocyte DNA.

  Retinoblastoma is a rare childhood cancer initiated by RB1 mutation or MYCN amplification, while additional alterations may be required for tumor development. However, the view on single nucleotide variants is very limited. To better understand oncogenesis, we determined the genomic landscape of retinoblastoma. We performed exome sequencing of 71 retinoblastomas and matched blood DNA. Next, we determined the presence of single nucleotide variants, copy number alterations and viruses. Aside from RB1, recurrent gene mutations were very rare. Only a limited fraction of tumors showed BCOR (7/71, 10%) or CREBBP alterations (3/71, 4%). No evidence was found for the presence of viruses. Instead, specific somatic copy number alterations were more common, particularly in patients diagnosed at later age. Recurrent alterations of chromosomal arms often involved less than one copy, also in highly pure tumor samples, suggesting within-tumor heterogeneity. Our results show that retinoblastoma is among the least mutated cancers and signify the extreme sensitivity of the childhood retina for RB1 loss. We hypothesize that retinoblastomas arising later in retinal development benefit more from subclonal secondary alterations and therefore, these alterations are more selected for in these tumors. Targeted therapy based on these subclonal events might be insufficient for complete tumor control.

  Study EGAS00001001690

• Single Cell Multiome ATAC + Gene Expression sequencing

  The SHH medulloblastoma tumor 7316-178 was received through the Childhood Brain Tumor Network (CBTN). From the patient tumor, disassociated cryopreserved cells stored in 10% DMSO/FBS were used. At least 50 mg of tissue (1 M cells) was used for both samples. Disassociated cells were prepared for Single Cell Multiome ATAC + Gene Expression sequencing (10× Genomics) according to the manufacturer’s instructions. Sequencing was performed on an Illumina NovaSeq S4 200 to a depth of at least 250 M reads for snATAC-seq and 200 M reads for snRNA-seq.

  Dataset EGAD50000001515

• Whole exome sequencing of 27 Greenlanders

  The data contain whole exome sequencing of 27 Greenlanders in nine trios. Data were produced by Agilent SureSelect capture followed by paired-end Illumina HiSeq 2000 sequencing to a depth of 90.1X. More details on processing and analysis can be found in Moltke et al, Nature 2014 (PMID 25043022).

  Dataset EGAD00001003813

• EPITREAT pilot cohort

  Benchmark data set containing five tumor/normal pairs of non-small cell lung cancer (NSCLC) patients. Tissue pairs were screened with bisulfite (BS) sequencing, MeDIP methylation enrichment sequencing and RNA sequencing in order to identify differentially methylated and expressed spots in the genomes.

  Dataset EGAD00001003116

• GIS-LUNGTCR1-2016_WES-FASTQ

  This dataset contains FASTQ files for multi-region exome-sequencing of EGFR-mutant lung adenocarcinomas from Asian patient. There are 16 patients and 95 samples in total, including 16 controls and 79 tumors. Multiple runs for each sample, and 368 fastq in total. Please refer to the sample-ID from filename for merging.

  Dataset EGAD00001001978

• ChIP-sequencing in human monocyte differentiation

  This dataset consists of ChIP-seq data from human monocytes, monocyte-derived dendritic cells as well as monocyte-derived cells that were subjected to siRNA treatment targeting CTCF or RAD21. ChIP-sequencing was done for H3K27, RAD21 and CTCF. In total, the data set includes 120 samples.

  Dataset EGAD00001007954

• Human inflammatory cardiomyopathies following SARS-CoV2 infection and COVID-19 vaccination

  Title: The cellular and molecular responses in human inflammatory cardiomyopathies following SARS-CoV2 infection and COVID-19 vaccination. Abstract: Abstract: Myocarditis is a cardiac disorder with multiple etiologies characterised by inflammatory cell infiltration and can occur after SARS-CoV-2 infection or rarely following mRNA-based COVID-19 vaccination. The underlying cellular and molecular mechanisms driving these pathologies remain poorly understood.Here we performed single-nucleus-RNA-sequencing in left ventricular endomyocardial biopsies from patients with Non-COVID-19 myocarditis, following SARS-CoV-2 infection (Post-COVID-19) and COVID-19 vaccination (Post-Vaccination). We detected specific cytokine expression patterns highlighting a particular role of interferon-γ in Post-COVID-19 and upregulated IL16 and IL18 expression as a Post-Vaccination hallmark. While the myeloid response was similar between groups, CD4+T-cell proportions were higher in Post-Vaccination and cytotoxic CD8+T and NK cells expanded in Post-COVID-19. Endothelial cells showed gene expression changes suggestive of vascular barrier function deficiency in Post-COVID-19 and angiogenesis response to cardiac inflammation in all groups. Together, our results illuminate shared and distinct cellular and molecular architectures of Non-COVID-19, Post-COVID-19 and Post-Vaccination associated myocardial inflammation in human hearts.

  Study EGAS50000000769

• DNA_repair_in_BLM_deficient_hiPSCs

  We are aiming to investigate repair of a double strand break (DSB) within the genome in the presence and absence of the BLOOM protein. Zinc Finger Nucleases introduce DSBs at specified loci within the genome. Using sequencing we will assess the size of the deletion following repair. Protocol1. Transfect normal and BLOOM deficient human iPS cells with ZFNs, using AMXA2. Harvest cells after 5 days3. Perform column extraction of DNA4. PCR-amplify the ZFN region 5. Sequence and analyse repair of the DSBThis 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 EGAS00001000740

• Results of RNA sequencing from all patients/samples

  Results of sequencing the targeted RNA-seq panel of breast cancer patients and controls. This dataset comprises of FASTQ files of 295 samples (both breast cancer patients and controls) and the results of mapping the FASTQ files to the reference human genome (hg38) available in a form of raw gene expression matrix.

  Dataset EGAD50000000017

• DESIGN II HNSCC RNA-Seq

  RNA-Seq data of 28 HPV-negative HNSCC specimens from patients treated at the Netherlands Cancer Institute (Amsterdam), VU Medical Centre (Amsterdam) or MAASTRO Clinic (Maastricht) in The Netherlands. HNSCC biopsy samples were obtained prior to treatment (chemo-radiotherapy) for the prospective study within the DESIGN project and used for polyA mRNA sequencing.

  Dataset EGAD00001005722

• Cancer Genomics of the Kidney

  The aim of CAGEKID is to carry out comprehensive detection of DNA markers for conventional (clear cell) renal carcinoma. The project includes complete analysis of somatic and constitutional DNA variation, methylation patterns and expression in a large number of constitutional/tumor pairs. CAGEKID is a part of the International Cancer Genome Consortium, ICGC.

  Dataset EGAD00001004018

• Congenital anosmia 2

  Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). Here we obtained genomic DNA from families with multiple individuals with anosmia, suggesting they are congenital. These include those inherited in a manner consistent with dominant and recessive alleles. We have sequenced the exomes of both affected and unaffected family members on the Illumina platform.

  Dataset EGAD00001002228

• Multiple Myeloma ChipSeq data on six histone modifications

  The data contained in this dataset is ChipSeq BAM files aligned to reference genome hg38. The ChipSeq was based on a combination of six histone modifications as follows: H3K4me1, H3K4me3, H3K9me3, H3K27me3, H3K27Ac and H3K36me3. The samples are patient-derived xenografts generated by passaging primary patient CD138+ selected cells through the SCID-rab myeloma mouse model.

  Dataset EGAD00001008353

• Single MII oocyte mRNA expression from women

  This dataset contains 14 paired-end FASTQ sequences from mRNA-Seq on single human M-II stage oocytes that were collected from ovarian tissue from unstimulated patients undergoing fertility preservation treatments due to cancer diagnoses, which did not influence ovarian function. Cumulus-oocyte-complexes were matured in vitro according Gruhn et al (Science 365: 1466-1469) and short term flash frozen prior to lysis, RNA extraction, full length cDNA preparation and amplification using the Ultra-low-input SMART-Seq2 v4 kit from Takara Clonetech. Further, these cDNA were used to prepare libraries for sequencing according the Nextera XT DNA library preparation kit from Illumina

  Dataset EGAD00001005971

• Harnessing_transposons_for_drug_resistance_gene_discovery_in_cancer

  This study involves a forward genetic screen to identify common insertion sites in drug resistant clones. We will be utilising piggybac transposon systems in order to generate multiple drug resistant clones in a range of human cancer cell lines.

  Study EGAS00001000468

• Distinct portrayal of lesions in synchronous multifocal lung adenocarcinoma revealed by genome sequencing

  Distinguishing multiple primary lung cancers in the synchronous multifocal intrapulmonary lesions has important significance on clinical staging and therapeutic decision. To investigate genomic aberration profiles, we applied whole genome and whole exome sequencing, and microarray-based comparative genomic hybridization on 15 intrapulmonary tumors derived from six patients with synchronous multifocal lung cancers having similar histological diagnosis. Any pair of intrapulmonary tumors in a single patient, which shared the identical genetic background and environment, showed an extinctive heterogeneity between each other. Phylogenetic relationship analysis indicated an independently branched evolution among all the tumors, suggesting they were multiple primary lung cancers. EGFR or KRAS mutations were found in 7 or 3 out of the 15 tumors, from 3 or 2 patients, respectively. Somatic mutational heterogeneity of these two genes in a single patient was also observed. Our analysis indicates genomic aberration profiling is valuable for identification of multiple primary lung cancer, especially when high histopathological concordance was observed between lesions. We also suggest a thoroughly molecular diagnosis against therapeutic target genes should be taken for each accessible nodule before making a plan for adjuvant therapy.

  Study EGAS00001001572

• Efficacy and safety of entrectinib in patients with ROS1-positive advanced/metastatic non-small cell lung cancer (NSCLC) from the Blood First Assay Screening Trial (BFAST)

  BFAST is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations, identified by blood-based molecular testing. We present data from Cohort D (ROS1-positive). Patients ≥18 years old with stage IIIB/IV, ROS1-positive NSCLC detected by blood-based testing, received entrectinib 600 mg daily. At data cut-off (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint; the confirmed objective response rate (ORR) by investigator was 81.5% which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR: 73.4%, data cut-off May 2019, ≥12 months follow-up). The safety profile of entrectinib was consistent with prior reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing and support the clinical value of blood-based testing to inform clinical decision-making.

  Study EGAS50000000105

• MutWP1: CRUK Grand Challenge Mutographs of Cancer: Oesophageal adenocarcinoma

  The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, the International Agency for Research on Cancer is coordinating the recruitment of 5000 individuals with cancer (colorectal, renal, pancreatic, oesophageal adenocarcinoma or oesophageal squamous cancers) across 5 continents to explore whether different mutational signatures explain marked variation in incidence. In brief, through an international network of collaborators around the world, biological materials are collected, along with demographic, histological, clinical and questionnaire data. Whole genome sequences of tumour-germline DNA pairs are generated at the Wellcome Trust Sanger Institute (40X and 20X depth respectively). Somatic mutational signatures are subsequently extracted by non-negative matrix factorisation methods and correlated with risk factors data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development. This dataset contains all the data available for this study on 2021-09-27.

  Dataset EGAD00001006083

• International consensus definition of DNA methylation subgroups in juvenile myelomonocytic leukemia

  Known clinical and genetic markers have limitations in predicting disease course and outcome in juvenile myelomonocytic leukemia (JMML). DNA methylation (DNAme) patterns in JMML have correlated with outcome across multiple studies, suggesting it as a biomarker to improve patient stratification. However, standardized approaches to classify JMML based on DNAme patterns are lacking. We therefore sought to define an international consensus for DNAme subgroups in JMML and develop classification methods for clinical implementation.

  Study EGAS00001004682

• Immune Profiles Study

  This study assesses glioma patient blood methylation longitudinally beginning pre-surgery through other clinically important timepoints. Progression and survival are studied in relation to methylation derived immunologic profiles and other characteristics. For this study, patients scheduled for surgery at University of California San Francisco (UCSF) for a possible newly diagnosed glioma (grades 2-4) or recurrent grade 2/3 glioma were consented and enrolled. Patients had blood collected pre-surgery and, if the pathology results confirm a glioma, every few weeks or months during their treatment (up to 30 total timepoints). Blood immunomethylomic profiles were measured at these timepoints to assess associations with glioma patient outcomes, clinical measures, other known prognostic markers, and imaging characteristics.

  Study phs002998

• Chordoma_Targeted_Sequencing_Study

  This Study uses a focused bespoke bait pull down library method to target findings of Chordoma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples.

  Study EGAS00001000280

• Osteosarcoma_Targeted_Sequencing_Study

  This Study uses a focused bespoke bait pull down library method to target findings of Osteosarcoma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples.

  Study EGAS00001000278

• Meningioma_Targeted_Sequencing_Study

  This Study uses a focused bespoke bait pull down library method to target findings of Meningioma whole genome and whole exome sequencing studies in order to validate findings. This method will also be used on a larger set of tumour only samples in order to find precedence of these findings in a larger set of patient samples.

  Study EGAS00001000282

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

  We generated the first 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.

  Study EGAS50000000735

• Analysis of translatome, truncating mutations, lncRNA, circRNA and microproteins of 80 human DCM cases and controls

  The regulation of gene expression in healthy and diseased human tissues is incompletely understood and has primarily been studied on the transcriptional level. Here, we quantify the impact of translation on gene expression and annotate novel translational events in 80 human hearts. These include 65 tissues from patients with dilated cardiomyopathy (DCM) - the most common cause of heart transplantation – and 15 unaffected controls. We show that translational regulation modulates disease-associated molecular processes. Further, we evaluate ribosome dynamics at protein truncating variants revealing incomplete termination of translation at titin-truncating variants (TTNtv) that commonly cause DCM. Finally, we identify dozens of unknown microproteins translated from lncRNAs and circRNAs and link these to mitochondrial processes. Several microproteins are expressed from lncRNAs with previously demonstrated function, suggesting a dual coding and noncoding role. This resource will stimulate novel functional investigations into cardiac biology in health and disease and may serve as a blueprint for characterizing the translational landscape of other human tissues.

  Study EGAS00001003263

• The Neonatal Microbiome and Necrotizing Enterocolitis

  The Neonatal Microbiome and Necrotizing enterocolitis (NEC) study is a multi-centered case control study testing the hypothesis that NEC is a direct or indirect consequence of the enteric biomass, its products, or both. Very low birth weight infants (VLBW; birth weight ≤ 1500 grams) admitted to the neonatal intensive care unit are prospectively followed over the first 5 week or until they reach 36 weeks gestation, whichever occurs later. VLBW infants with a lethal clinical condition are excluded. Over the course of the study period, prospective samples are obtained on all infants, and include all stools, and weekly blood samples, palm and oral swabs. Clinical data is collected over the course of the entire hospitalization. Cases are identified based on Bell's staging for NEC, requiring Bell's stage II (abdominal clinical signs and radiographic evidence of pneumatosis, portal venous gas or pneumoperitoneum). Controls are identified from the pool of prospectively enrolled subjects, matching for gestational age, birth weight, post-natal age and birth date. The microbial components of stool and its products before and at the onset of NEC, are then compared between cases and controls. The Aims of this proposal are to (1) conduct a case cohort study in which we compare clinical data and biological specimens from cases and well-matched controls; (2) determine if the kind and density of intestinal biomass, its gene content, and transcriptional activity are associated with, and potential determinants of, NEC; and (3) determine if host risk alleles for intestinal inflammation play a role in the development of NEC.

  Study phs000247

• Transcriptomic Profiling of Oropharyngeal Squamous Cell Carcinoma

  The study is a retrospective transcriptomic profiling of oropharyngeal squamous cell carcinoma. The pathologic database was queried for squamous cell carcinoma tumors originating from the anatomic oropharynx (tonsil or tongue base) with available samples from surgical archives. This retrospective RNA sequencing cohort included cases dating prior to the routine implementation of p16 immunohistochemistry (IHC) testing at our institution, therefore, p16 status was not required for inclusion in this study. Formalin-fixed paraffin-embedded (FFPE) tissue samples were sent to the UNC Lineberger Comprehensive Cancer Center (LCCC) Translational Genomics Lab (TGL) for RNA isolation using the Maxwell 16 MDx Instrument (Promega AS3000) and the Maxwell 16 LEV RNA FFPE Kit (Promega AS1260) following the manufacturer's protocol (Promega 9FB167). After a pathology review of a hematoxylin and eosin (H&E) stained slides to identify tumor area, RNA was extracted from unstained slides using macrodissection. Total RNA quality was measured using a NanoDrop spectrophotometer (Thermo Scientific ND-2000C) and a TapeStation 4200 (Agilent G2991AA). Total RNA concentration was quantified using a Qubit 3.0 fluorometer (Life Technologies Q33216). Libraries were prepared with Illumina TruSeq Stranded Total RNA with Ribo-Zero protocol. Libraries were sequenced on an Illumina HiSeq2500 sequencer. Paired end read data, with read lengths of 75 were collected.

  Study phs002935

• Targeted long-read snIso-Seq of the human brain in neurodegenerative diseases

  Nuclei were extracted from postmortem human brain, and cDNA libraries were generated using the 10X Genomics 3' v3.1 kit. Prior to fragmentation, 75% of the library was reserved for long-read sequencing. This unfragmented library was used for target enrichment with a custom 50 gene probe panel from Twist Biosciences. The resulting amplified cDNA libraries were sequenced on a Sequel II. The files provided have undergone CCS generation, and we recommend following the guidelines in https://isoseq.how/ for further analysis starting with removal of primers using lima. The primer sequences that should be supplied are the Read 1 and TSO primers from the 10X Genomics kit.

  Dataset EGAD50000000179

• Immunogenomics of colorectal cancer response to immune checkpoint blockade

  Molecular and cellular determinants of response to immune checkpoint inhibitors are mostly unknown. Here we use whole exome, RNA and T cell receptor sequencing, imaging mass cytometry, immunohistochemistry and PD1-PDL1 interaction detection to profile 543 regions from 16 colorectal cancers (CRCs) subsequently treated with Pembrolizumab or Nivolumab. Independent of treatment response, CRCs express low levels of PD1 and PDL1 proteins and form less PD1-PDL1 complex than other cancers. Non hypermutated CRCs have no benefit from treatment, show WNT activation and low T cell infiltrates. Among hypermutated CRCs, those with durable benefit have clonal immunogenic alterations, clonally expanded T cells and potential for immune escape through dysfunctional antigen presentation. Responsive tumours are enriched in PD1-expressing cytotoxic and proliferating CD8 T cells and PDL1-expressing antigen presenting macrophages, which form high-density clusters of interacting cells. Our study shows that immune checkpoint inhibitors are most effective in highly infiltrated CRCs where they may release the interactions between macrophages and CD8 T cells thus promoting their priming and expansion in intra-tumour niches.

  Study EGAS00001004438

• RNA sequencing in primary inflammatory (TPP) macrophages following deletion of a disease-associated gene desert at chr21q22, disruption of ETS2, or treatment of ETS2-edited macrophages with a HIF1α stabiliser.

  This dataset comprises raw RNA sequencing data (FASTQs) from primary inflammatory (TPP) macrophages that were unedited (non-targeting control, NTC), edited to delete the disease-associated chr21q22 enhancer region (n=5), or edited to disrupt ETS2 with 1 of 2 independent gRNAs (n=9). We also performed RNA-sequencing in NTC or ETS2-edited TPP macrophages that were treated for 12 hours with vehicle (DMSO) or roxadustat (30 uM, n=3). Macrophages were detached using Accutase and lysed. RNA was extracted from cell lysates using an AllPrep DNA/RNA Mini Kit (Qiagen). Sequencing libraries were prepared from 10ng RNA using the SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian (Takara) following the manufacturer’s instructions. The quality and molarity of all libraries was assessed using a BioAnalyzer 2100 and the libraries were sequenced on a NextSeq500. Raw data are provided as 50 bp paired-end Illumina reads.

  Dataset EGAD00001011338

• Fixed single-cell transcriptomic characterization of human radial glial diversity

  The human neocortex is created from diverse intermixed progenitors in the prenatal germinal zones. These progenitors have been difficult to characterize since progenitors - particularly radial glia (RG) - are rare, and are defined by a combination of intracellular markers, position and morphology. To circumvent these problems we developed a method called FRISCR (Fixed and Recovered Intact Single Cell RNA) for transcriptome profiling of individual fixed, stained and sorted cells. We developed and validated FRISCR on human embryonic stem cells. We then profiled primary human RG (96 - 132 days post conception) that constitute only 1% of the mid-gestation cortex. These RG could be classified into ventricular zone-enriched RG (vRG) that express ANXA1 and CRYAB, and outer subventricular zone-localized RG (oRG) that express HOPX. Our study identifies the first markers and molecular profiles of vRG and oRG cells, and provides an essential step for understanding molecular networks driving the lineage of human neocortical progenitors. Reprinted from Thomsen et. al. Nature Methods (2015), with permission from Nature Publishing. Human embryonic stem cell data may be obtained through NCBI's GEO database, using accession number GSE71858. Raw data from one human sample that was not consented to be released to dbGaP may be obtained directly from the authors of Thomsen et. al., 2015.

  Study phs001016

• Finding structural variation from the patient-derived xenografts of pediatric T-cell leukemia at the single-cell level

  In this study, we aimed to identify somatic structural variation of T-cell acute lymphoblastic leukemias (T-ALLs_ from patient-derived xenografts (PDX) at the single-cell level. For this purpose, we performed strand-specific single-cell sequencing of PDX-derived T-ALL relapse samples from two juvenile patients (P1, P33). To validate structural variation detected via scTRIP, we profiled whole exome sequencing (WES) data from P33 (samples taken during initial disease, remission, relapse), and mate-pair sequencing data from P1 (relapse).

  Dataset EGAD00001004499

• T-cell receptor targeting FLT3 D835Y mutation study

  We identified a T-cell receptor (TCR) reactive to the recurrent FLT3 D835Y mutation in the tyrosine-kinase domain. To validate the elimination efficacy of leukemia cells, we transplanted human acute myeloid leukemia (AML) cells with FLT3 D835Y mutations into NSG-SGM3 mice and treated either with TCR FLT3 D835Y redirected T cells, or control TCR (TCR 1G4). After treatment, we performed flow sorting of AML blasts (CD3-CD19-) and primary T cells (CD3+CD8+orCD4+CD19-CD33-) and performed whole-exome sequencing.

  Dataset EGAD00001011258

• Whole exome sequencing study of cholesteatoma patients from affected families

  This study used whole exome sequencing on 21 patients with cholesteatoma from 10 families in order to identify variants that may attribute to cholesteatoma aetiology. Exomes were enriched for using hybridisation selection and subject to DNA-sequencing. This datasets is formed of two batches as they were sequencing at different times. Batch-1 exomes were selected for using Nimblegen capture (4-plex) and sequenced on Illumina Hiseq 4000 and batch-2 was exome selected using Agilent SureSelect Human All Exon v6 and sequenced on the Illumina NovaSeq 6000. All samples within the same family were processed within the same batch. This dataset is comprised on BAM files mapped using cgpMAP v3.2.0 (bwa-mem) using the GRCh38.

  Dataset EGAD00001008671

• KAT6A and KAT7 Histone Acetyltransferase Complexes Are Molecular Dependencies and Therapeutic Targets in NUP98-Rearranged Acute Myeloid Leukemia

  NUP98 fusion oncoproteins (FOs) are a hallmark of childhood acute myeloid leukemia (AML). NUP98 FOs drive leukemogenesis through phase-separated condensate formation and maintenance of an active chromatin landscape at stem cell-associated genes in cooperation with epigenetic regulators. Here we show that MYST family histone acetyltransferase (HAT) complex proteins including KAT6A/MOZ, KAT7/HBO1, and the common KAT6A/7 complex subunit BRPF1 associate with NUP98 FOs on chromatin and within condensates. MYST HATs are molecular dependencies in NUP98-rearranged (NUP98-r) leukemia, and genetic inactivation or pharmacologic inhibition of Kat6a and Kat7 impairs NUP98-r cell fitness. KAT6A/7 inhibition decreased global H3K23ac levels, displaced NUP98::HOXA9 from chromatin at the Meis1 locus, and led to myeloid cell differentiation. Additionally, KAT6A/7 inhibition decreased leukemic burden in multiple NUP98-r leukemia xenograft mouse models, synergized with Menin inhibitor treatment, and was efficacious in Menin inhibitor-resistant cells. In summary, we show that MYST family HATs are therapeutically actionable dependencies in NUP98-r AML.

  Study EGAS50000001075

• Copy-Number Analysis of Understudied Black Women Ovarian Cancers

  Two general types of genetic alterations drive cancer progression: mutations and copy number alterations (CNAs). With the exception of p53, single nucleotide variant mutations (here, simply "mutations") are not drivers of 80% of tumors within the most frequent and deadly histotype of ovarian cancer: serous ovarian cancer (SOC). Rather, CNAs are more prevalent in SOC than any other cancer type studied by phs000178 The Cancer Genome Atlas (TCGA). Fully two-thirds of genes are altered by CNAs in the average SOC. Bioinformatic methods have shown that these CNAs modulate specific molecular pathways, such as autophagy, and this finding enabled effective pathway-targeted therapies1. Unfortunately, TCGA ovarian cancer data lacks racial diversity. Only 6% of SOC tumors (n=32) studied are from African origin. Black women diagnosed with ovarian cancer are more likely to die from their disease than white women. Five-year survival after diagnosis is 31% among blacks versus 42% among whites, and this disparity is seen in every age group and tumor stage distribution. Dr. Kelemen examined data from 365 white and 95 black ovarian cancer patients from the Hollings Cancer Center (HCC) Cancer Registry between 2000 and 2015 and found that black women had an 81% higher risk of death after diagnosis compared to white women (HR 1.81, 95% CI 1.35-2.43), independent of diagnosis center (98% were treated at HCC but half were diagnosed elsewhere), tumor stage, histology, extent of residual tumor remaining following surgery, insurance status, smoking, type of treatment for ovarian cancer, and age-adjusted Charlson comorbidity index. This disparity remained even when restricted to women who received the standard of care, surgery-chemotherapy sequence (HR 1.79, 95% CI 1.10-2.89). Despite receiving the same treatment, black race was still associated with inferior survival. A similar disparity has been reported by others, indicating that the HCC experience is representative of national data. Here, an additional set of high-grade serous ovarian cancer primary tumors were acquired from biorepositories with a focus on expanding data originating from African American women. Data were analyzed for copy-number alterations using exome sequencing and control-FREEC software.

  Study phs002313

• Understanding Determinants of Racial Disparities in Lung Cancer Incidence

  This is a nested case-control study designed to evaluate the association between common genetic variants and the risk of lung cancer. The study included 1258 cases and 1252 controls selected from the Southern Community Cohort Study (SCCS), a large, prospective observational cohort. Cases were identified from cancer registries across the catchment area of the SCCS. Cases and controls were frequency matched on age, sex, race, and enrollment site (community health center vs general population).

  Study phs003789

• RNA-seq analysis refines molecular subtypes of hepatocellular carcinoma

  This work aims to identify homogeneous and robust molecular subtypes in HCC based on a large, homogenous and well-annotated cohort. We performed RNA sequencing (RNA-seq) on 529 HCC from 461 patients collected mainly in France. Based on the consistency between genomic and transcriptomic data, we identified 9 robust HCC subtypes mainly based on driver mutations. We further characterized HCC subtypes using transcriptomic and clinicopathological features. Our study provided a robust molecular classification based on a large HCC dataset from a Western country, improving our understanding of the mechanisms of carcinogenesis and facilitating the development of genome-based precision medicine in HCC.

  Dataset EGAD00001015427

• Dissecting intratumor heterogeneity of nodal B cell lymphoma on the transcriptional, genetic, and drug response level

  Tumor heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is well-known to affect the efficacy of anti-cancer, most personalized treatment approaches do not account for intratumor heterogeneity. We addressed this issue by studying the heterogeneity of lymph node-derived B cell non-Hodgkin lymphoma (B-NHL) by single cell RNA-sequencing (scRNA-seq) and transcriptome-informed flow cytometry. We identified transcriptionally distinct malignant subclones and compared their drug response and genomic profiles. Malignant subclones of the same patient responded strikingly different to anti-cancer drugs ex vivo, which recapitulated subclone-specific drug sensitivity during in vivo treatment. Tumor infiltrating T cells represented the majority of non-malignant cells, whose gene expression signatures were similar across all donors, whereas the frequencies of T cell subsets varied significantly between the donors. Our data provide new insights into the heterogeneity of B-NHL and highlight the relevance of intratumor heterogeneity for personalized cancer therapies.

  Study EGAS00001004335

• ScRNA sequencing and snp-array genotyping of peripheral immune cells in Type 1 diabetes mellitus (T1DM)

  Type 1 diabetes mellitus (T1DM) is a prototypic endocrine autoimmune disease resulting from an immune-mediated destruction of pancreatic insulin-secreting beta-cells. A comprehensive immune cell phenotype evaluation in T1DM has not been performed thus far at the single. In this cross-sectional analysis, we generated a single-cell transcriptomic dataset of peripheral blood mononuclear cells (PBMCs) from 46 manifest T1DM (Stage 3) cases and 31 matched controls.Our study reveals a surprisingly strong systemic dimension at the level of immune cell network in T1DM, defines disease-relevant molecular subtypes and has the potential to guide non-invasive test development and patient stratification.

  Dataset EGAD50000000345

• Genomic Predictors of Response to Immune Checkpoint Therapy

  Immune checkpoint therapies, including monoclonal antibodies to programmed cell death-1 (PD-1) and cytotoxic % lymphocyte associated protein-4 (CTLA-4), yield durable clinical responses across many tumor types, including metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). However, predictors of response to these therapies in RCC are still unknown. Genomic characterization of large clinical cohorts of patients treated with anti-CTLA-4 and anti-PD-1 agents in melanoma and NSCLC have suggested that high mutational burden, high neoantigen burden, and high expression of certain genes in pre-treatment tumors may be associated with patient response to these therapies. In this study, we sought to investigate genomic predictors of response to anti-PD1 therapy in metastatic RCC in two independent clinical cohorts using whole exome and whole transcriptome sequencing.

  Study phs001493

• H014: HES5 mediates NOTCH signaling by interaction with AKT to drive liver carcinogenesis

  Notch signaling plays a pivotal role in liver development and aberrant Notch signaling may lead to hepatocellular (HCC) or cholangiocellular carcinoma (CCA) development. Using whole exome sequencing of 54 human HCC samples, we discovered 19 somatic missense mutations in 15 different Notch pathway genes affecting 24.6% (14 of 57) of patients. Prediction of functional impact of these Notch pathway mutations revealed HES5-R31G to have high relevance. We found HES5 to be strongly activated by Notch signaling. In vitro, HES5 reduced cell migration and clonogenicity and in vivo, HES5 inhibited MYC-dependent liver tumor formation. But together with AKT, HES5 increased liver tumor formation in a mouse model. HES5 directly binds to AKT and AKT expression leads to increase HES5 protein levels. Furthermore, HES5 exhibits a negative feed-back loop by inhibiting NOTCH1 and HES1 gene expression. In contrast, HES5-R31G appears to be non-functional possibly by loss of nuclear translocation

  Study EGAS00001003329

• Automated machine-learning approach for next generation profiling of sequence alterations, mutation burden, microsatellite instability, and structural variants in human cancers

  Sequence and structural alterations together with tumor mutation burden (TMB) and microsatellite instability (MSI) have been identified as biomarkers for the determination of response to targeted and immune checkpoint inhibitor therapies. However, widespread clinical adoption of these biomarkers has historically been limited due to barriers such as evidence of clinical utility and reimbursement. We have developed 2.2 Mb targeted NGS system and an automated machine-learning analysis approach (PGDx elio™ tissue complete, ETC) that has been FDA cleared for examination of 500+ cancer-related genes and 68 mononucleotide repeats for identification of sequence and structural alterations, TMB, and MSI in solid cancers in a clinical setting. We designed and trained this approach using sequence data from 4,174 cancers and >124,000 in silico alterations and evaluated the methodology in >2,550 tumor or non-cancerous normal samples. Independent analyses of ETC sequence changes in 440 formalin fixed paraffin embedded (FFPE) tumor or cell line samples using MSK-IMPACT™, FoundationOne®, and ddPCR revealed a positive percent agreement (PPA) >97% with high sensitivity as low as 3% mutant allele fraction. We observed high concordance between panel-wide and whole-exome TMB for 307 pan-cancer FFPE tumors (Pearson r=0.95, p < 0.0001) using samples with ≥20% tumor cellularity. Comparison of the mutation context and repeat-based MSI approach in ETC with a multiplex MSI PCR assay in 223 samples revealed a PPA of 99% and negative predictive agreement (NPA) >99%. We confirmed the accuracy and precision of TMB and MSI measurements across three independent laboratories (CV of <5% and average PPA >99%, respectively). Finally, evaluation of amplifications and translocations against DNA and RNA-based approaches exhibited >98% NPA and PPA of 86% and 82% respectively. These results demonstrate high analytical performance for determination of sequence and structural changes, TMB, and MSI using a targeted NGS panel and provide a scalable and facile approach for evaluating these biomarkers in a clinical laboratory.

  Study EGAS00001005556

• Singel-cell RNA sequencing and CUT&RUN sequencing of human RUNX2-deficient osteoblasts

  Runx2 is a master regulator of bone formation, and its dysfunction causes cleidocranial dysplasia (CCD) in humans. When iPS cells were generated from patients with CCD and Runx2-deficient iPS cells were generated using gene-editing techniques, abnormal laminopathy-like nuclei were observed. Runx2-deficient cells showed reduced Lamin A/C expression, but not protein levels. However, in Runx2-deficient cells, both the gene expression and protein levels of Nesprin-1 were reduced, perinuclear actin fibers were sparser, and nuclear stiffness was reduced. Forced expression of Lamin A/C increased nuclear stiffness but did not improve nuclear morphology. In contrast, the induction of Nesprin-1 expression alone normalized nuclear stiffness and restored nuclear morphology and perinuclear actin distribution. In Runx2-null cells, mechanical stress-induced phosphorylation of emerin was not observed. In contrast, forced expression of nesprin-1 in Runx2-null cells resulted in phosphorylation of emerin, indicating the restoration of intracellular tension. These observations were confirmed by atomic force microscopy. Therefore, the intracellular tension was inferred to pull the nuclear membrane into its normal shape. CUT&RUN assay and single RNA-seq analysis showed that an aberrant nuclear membrane caused loss of nuclear lamina gene regulation machinery, making the progression of normal osteogenic differentiation impossible; however, supplementation with Nesprin-1 restored gene regulation mechanisms and promoted pre-osteoblast formation with normal nuclear morphology. Nesprin-1 expression induced by Runx2 is essential for epigenetic regulation of the nuclear lamina. We propose CCD as a new type of laminopathy involving defective expression of Nesprin-1 regulated by Runx2.

  Study JGAS000663

• Transcriptome analysis of Familial dysautonomia patient cells treated with splice-regulating compounds

  In order to investigate familial dysautonomia patient fibroblasts in response to splice-regulating compounds, cells were treated with RECTAS or TG003 and transcriptome study was conducted by RNA-seq. Splicing profiles of cells in each condition were then analyzed.

  Study JGAS000170

• Transcriptome analysis of Fabry disease iPSC-derived cardiomyocytes treated with splice-regulating compound; RECTAS

  In order to investigate transcriptome profiles in response to splice-regulating compounds, iPSC-derived cardyomyocytes were treated with RECTAS and transcriptome study was conducted by RNA-seq. Splicing profiles of cells in each condition were then analyzed.

  Study JGAS000225

• Investigation of chromatin accessibility in clear cell renal cell carcinoma using ATAC-seq

  To identify regions of open and accessible chromatin in clear cell renal cell carcinoma (ccRCC), we performed ATAC-seq on the 786-O, A-498, UM-RC-2 ccRCC cell lines, as well as HK-2 normal renal epithelium cell line, cultured under normoxic (20% O2) and hypoxic (0.05% O2) conditions. Data are provided in raw fastq and processed narrowPeak fomats. Data were processed using the nf-core atacseq pipeline.

  Dataset EGAD50000001885

• Genomic Landscape of Malignant Peripheral Nerve Sheath Tumor-like Melanoma

  Malignant peripheral nerve sheath tumor (MPNST)-like melanoma is a rare malignancy with overlapping characteristics of both neural sarcoma and melanoma. The genomics of MPNST-like melanoma have not been previously described. In this study, we performed whole exome sequencing analysis in 8 samples from 6 patients diagnosed with MPNST-like melanoma. Our results demonstrate that, although MPNST-like melanoma shares oncogenic alterations common to both cutaneous melanoma and MPNST, it also presents unique genomic alterations not previously described in neither of the malignancies.

  Dataset EGAD00001006999

• TK-EPN862 - Patient-derived xenograft model of Posterior Fossa A Ependymoma - RNAseq

  In Vivo Loss of Tumorigenicity in a Patient-Derived Orthotopic Xenograft Mouse Model of Ependymoma. Whitehouse et al. 2023 Frontiers in Oncology. We describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of posterior fossa A (PFA) EPN, derived from a metastatic cranial lesion. Patient and PDOX tumors were analyzed using RNA sequencing. RNAseq data (paired end) provided here correspond to Primary tumour, two metastatic lesions (one spinal, one cranial), and a patient-derived xenograft derived from the patient.

  Dataset EGAD00001009870

• Chromatin Accessibility Landscape of Human Pancreatic Ductal Adenocarcinoma (PDAC)

  Therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we discovered a signature of 1092 chromatin loci displaying differential accessibility between patients with disease-free survival (DFS) < 1 year and patients with DFS > 1 year. Using this signature, we further develop a chromatin accessibility microarray methodology termed “ATAC-Array”, an easy-to-use platform obviating the time and cost of next-generation sequencing. PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.

  Study phs002394

• Clonal tracing with somatic epimutations reveals dynamics of blood aging

  In this study, we generated comprehensive single-cell multi-omic datasets from bone marrow samples collected from 13 donors spanning a wide age range. We applied the scTAMseq protocol to profile DNA methylation and nuclear mutations obtained from 7 total bone marrow aspirates (donors A.1-A.7) and 6 CD34+-enriched bone marrow samples ((donors B.1-B.5 & X.1). Complementary surface marker expression data were acquired by integrating CITE-seq into the scTAMseq workflow (scTAMseq_prot). Targeted RNA sequencing (scTAMARA_rna) was performed alongside scTAMARA_DNA on one CD34+-enriched sample (X.1). Additionally, a dedicated mitochondrial panel (TAMITO_seq) was employed on a peripheral blood sample from a healthy donor (X.2) to assess mitochondrial heterogeneity and facilitate lineage tracing.

  Study EGAS00001008056

• Phase 1/2 Study of the Indoleamine 2,3-Dioxygenase 1 Inhibitor Linrodostat Mesylate Combined With Nivolumab or Nivolumab and Ipilimumab in Advanced Solid Tumors or Hematologic Malignancies

  Purpose: To evaluate the safety, efficacy, pharmacokinetics, pharmacodynamics, and biomarker data of linrodostat mesylate, a selective, oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, combined with nivolumab ± ipilimumab in advanced solid tumors and hematologic malignancies. Patients and Methods: In this phase 1/2 study, patients received once-daily (QD) linrodostat (part 1 [escalation], 25-400 mg; part 2 [expansion], 100 or 200 mg) plus nivolumab (480 mg every [Q] 4 weeks [W] or 240 mg Q2W) or triplet therapy (part 3, linrodostat 20-100 mg QD; nivolumab 360 mg Q3W or 480 mg Q4W; ipilimumab 1 mg/kg Q6W or Q8W). Endpoints included safety and efficacy (co-primary; parts 2, 3), pharmacokinetics, pharmacodynamics, biomarkers, and efficacy (part 1). Results: Fifty-five, 494, and 41 patients were enrolled in parts 1, 2, and 3, respectively. Linrodostat exposures exceeded predicted therapeutic target concentrations starting at 50 mg. Rates of grade 3/4 adverse events were 50.1%-63.4%. The maximum tolerated linrodostat dose was 200 mg; dose-limiting toxicities were primarily immune related. Responses were observed across different cohorts, study parts, and tumor types, particularly in immunotherapy-naive patients. Kynurenine decreased with linrodostat + nivolumab, regardless of response. In contrast, interferon gamma (IFN-γ) gene expression signature was associated with response; in nonmelanoma patients, a composite of low tryptophan 2,3-dioxygenase (TDO2) gene expression plus high IFN-γ signature was associated with response. Conclusions: Linrodostat + nivolumab ± ipilimumab demonstrated a manageable safety profile. Kynurenine changes supported IDO1 pathway inhibition but did not correlate with response. A composite biomarker of low TDO2 expression plus high IFN-γ gene expression may predict response to linrodostat + nivolumab.

  Study EGAS50000000710

• Copy numbers in resectable gastric cancer treated with surgery alone

  Purpose: Gastric cancer is a heterogeneous disease requiring stratification to recognize its underlying biology and variable clinical outcome. The Cancer Genome Atlas (TCGA) recognizes four molecular subgroups: Epstein-Barr virus positive (EBV+) and microsatellite instable (MSI) with superior survival compared to genomically stable (GS) and chromosomal instable (CIN). Since classification criteria to distinguish GS from CIN were not defined, alternative markers such as Lauren’s histopathology or CDH1/p53 immunohistochemistry are commonly applied. Here we compared survival of gastric cancer subgroups determined by four methods. Experimental Design: EBV- and microsatellite stable tumors from a total of 309 patients treated with surgery alone were assigned to subgroups by: (i) specific copy number aberrations as determined by TCGA (GS or CIN), (ii) genome instability index (GII; high or low), (iii) Lauren’s classification (diffuse or intestinal), and (iv) CDH1/p53 immunohistochemistry (IHC; aberrant CDH1, normal-, or aberrant p53 expression). Subgroups were associated with cancer-related survival (CRS). Results: Five-year CRS was 42.0% for diffuse and 49.5% for intestinal type tumors, and 57.8% for GS and 41.6% for CIN tumors. Classification by GII or CDH1/p53 IHC did not correlate with CRS. The combination of TCGA and Lauren classifications resulted in four distinct subgroups. Five-year CRS for GS-intestinal (n=24), GS-diffuse (n=57), CIN-intestinal (n=142) and CIN-diffuse (n=86) was 61.4%, 56.5%, 47.6%, and 31.5%, respectively. Conclusions: TCGA’s GS and CIN have additional prognostic value to Lauren’s diffuse and intestinal subgroups in gastric cancer. GS-intestinal, GS-diffuse, CIN-intestinal and CIN-diffuse constitute biologically distinct entities and are suggested as stratification variables for future studies.

  Study EGAS00001007394

• SmMIP-tools:a computational toolset for processing and analysis of single-molecule molecular inversion probes derived data

  Single-molecule molecular inversion probes (smMIPs) provides a modular and cost-effective platform for high-multiplex targeted next-generation sequencing (NGS). Nevertheless, translating the raw smMIP-derived sequencing data into accurate and meaningful information currently requires proficient computational skills and a large amount of computational work, prohibiting wide-scale adoption of smMIP-based technologies. To enable easy, efficient, and accurate interrogation of smMIP-derived data, we developed SmMIP-tools, a computational toolset that combines the critical analytic steps for smMIP data interpretation into a single computational pipeline. Here, we describe in detail two major components of the software. The first is a read processing tool that performs quality control steps, generates read-smMIP linkages and retrieves molecular tags. The second is an error-aware variant caller capable of detecting single nucleotide variants (SNVs) and short insertions and deletions (indels). Using a cell-line DNA dilution series and a cohort of blood cancer patients, we benchmarked SmMIP-tools and evaluated its performance against clinical sequencing reports. We anticipate that SmMIP-tools will increase accessibility to smMIP-technology, enabling cost-effective genetic research to push personalized medicine forward.

  Study EGAS00001005359

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

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

  Dataset EGAD00001011048

• A benchmarking resource for NGS testing of cancer predisposition genes

  A benchmarking resource of 639 individuals, to assess the analytical sensitivity of cancer predisposition gene (CPG) testing.The dataset includes sequencing data generated using the TruSight Cancer Panel (TSCP) a targeted NGS assay for analysis of CPGs and orthogonally generated data supporting at least one pathogenic variant in a CPG for a total of 645 pathogenic CPG variants.The set of pathogenic CPG variants includes strong representation of some of the most challenging types of pathogenic variants, with 339 indels, including 16 complex indels and 24 insertions or deletions with length greater than 5bp, and 74 exon CNVs, including 23 single exon CNVs. There are 502 pathogenic variants in BRCA1 or BRCA2, making this an important first-line validation dataset for laboratories performing NGS testing of BRCA1 and BRCA2.

  Study EGAS00001002993

• Collaborative Cohort of Cohorts for COVID-19 Research (C4R): REasons for Geographic and Racial Differences in Stroke (REGARDS)

  Cohort DescriptionThe REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort is one of the nation's largest, most comprehensive population-based cohorts, and it uses innovative home- and telephone-based data collection. REGARDS centrally recruited and initially examined 30,239 Black and White men and women aged ≥45 years in 2003-7 to understand why Southerners and Black Americans have a higher incidence of stroke and related diseases that affect brain health.Data Being Submitted Wave 1 questionnaire data includes 397 variables for 8109 REGARDS participants in C4R. Wave 2 questionnaire data includes 448 variables for 6421 REGARDS participants in C4R. Dried Blood Spot/Serosurvey data includes 7 variables for 4058 REGARDS participants in C4R. Derived data includes 43 variables for 8606 REGARDS participants in C4R. Phenotype data includes 113 variables for 7880 REGARDS participants in C4R.

  Study phs002919

• Center for Inherited Disease Research (CIDR)-National Institute on Aging (NIA) Whole Exome Analysis of Ehlers-Danlos Syndrome

  The Ehlers-Danlos syndromes (EDS) are a family of hereditary disorders of connective tissue characterized by joint hypermobility and skin involvement with soft, translucent, stretchy skin, and atrophic scarring. To date, over 12 different types of EDS are known, and the genes causing almost all of them have been found. However, the gene(s) underlying the most common of Ehlers-Danlos syndrome, known as the hypermobile type, remain elusive. The hypermobile type of Ehlers-Danlos syndrome is associated with multiple co-morbidities, including dysautonomia, chronic musculoskeletal pain, gastrointestinal dysmotility, mast cell activation and multiple neurologic complications. Affected persons often suffer from chronic fatigue and may be chronically disabled. While the precise frequency of the condition is not known, it may be as common as between 1/500 and 1/1000 persons. There is a significant overlap with the phenotype of fibromyalgia, and multiple persons diagnosed with fibromyalgia may well have the hypermobile type of Ehlers-Danlos syndrome. The phenotype of hypermobile EDS segregates as a single dominant trait with complete penetrance, variable expressivity, and a markedly evolving phenotype over time. Identification of the genetic cause of this hereditary disorder has the potential to inform rational therapy for this disabling condition. It is hoped that the insight into the pathogenesis of the hypermobile type of EDS will lead to a similar breakthrough in therapy for this disorder. Toward this end, whole exome sequencing (WES) of DNA from a total of 167 patients will be performed at the Center for Inherited Disease Research (CIDR) to identify genes underlying the hypermobile type of Ehlers-Danlos syndrome and those with EDS of an uncharacterized type.

  Study phs001779

• Colorectal cancer GWAS on the Spanish population

  Data on Affymetrix 6.0 arrays for Genome-Wide Association Study of colorectal cancer in the Spanish population. Additionally, geographical origin for each sample is provided, which constitutes the largest to-date Spanish genomic sample population

  Dataset EGAD00010001715

• Dynamic human admixture histories over the past ~1,300 years at the northern Himalayan frontier

  Whole-genome sequencing data from ten present-day individuals from Himachal Pradesh, India. DNA from these ten present-day individuals was converted to double-stranded libraries and sequenced on Illumina NovaSeq 6000 in 150 bp paired-end mode. The dataset consists of raw fastq and bam (hg19) files.

  Dataset EGAD50000001925