3413 results for "*geneti*"

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• HV31 - Illumina PCR-free sequencing

  Illumina PCR-free sequencing data for individual HV31 generated using DNA from peripheral blood mononuclear cells, to a sequencing depth of ~44×. Sequencing was performed at the Wellcome Centre for Human Genetics on the Illumina Novaseq platform.

  Dataset EGAD00001007042

• HV31 - Oxford Nanopore PromethION long-read sequencing

  Oxford Nanopore long-read sequencing data for individual HV31 generated using DNA from CD14+ monocytes, to a sequencing depth of ~63×. Sequencing was performed at the Wellcome Centre for Human Genetics using the Oxford Nanopore PromethION platform.

  Dataset EGAD00001007043

• Peruvian Genome Project

  Through the Peruvian Genome Project we generate and analyze the high coverage genomes of 150 individuals where the majority have >90% Native American ancestry and explore questions at the interface of evolutionary genetics, history, anthropology, and medicine. This is the most extensive sampling of high-coverage Native American and mestizo whole genomes to date. Reference: https://doi.org/10.1073/pnas.1720798115

  Dataset EGAD00001007082

• Mutational landscape of normal epithelial cells in Lynch Syndrome patients

  Lynch Syndrome (LS) is an autosomal dominant disease conferring a high risk of colorectal cancer due to germline heterozygous mutations in a DNA mismatch repair (MMR) gene. Although cancers in LS patients show elevated somatic mutation burdens, information on mutation rates in normal tissues and understanding of the trajectory from normal to cancer cell is limited. Here we whole-genome sequenced 152 crypts from normal and neoplastic epithelial tissues from LS patients. In normal tissues the repertoire of mutational processes and mutation rates were similar to those found in wild type individuals. A morphologically normal colonic crypt with an increased mutation burden and mutational signatures consistent with MMR deficiency was identified, which may represent a very early stage of LS pathogenesis. Phylogenetic tress of tumour crypts indicated that the most recent ancestor cell of each tumour was already MMR deficient and had experienced multiple clonal evolution cycles. This study demonstrates the genomic stability of epithelial cells with heterozygous germline MMR gene mutations and highlights important differences in the pathogenesis of LS from other colorectal cancer predisposition syndromes.

  Dataset EGAD00001008092

• May 2021 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  May 2021 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001008100

• August 2021 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  August 2021 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001008101

• Genetic variability in exon 1 of the glucocorticoid receptor gene NR3C1 is associated with postoperative complications

  Bisulfite sequencing of a 3kb region within the CpG island of the NR3C1 exone 1 was performed with Illumina Miseq. 24 samples from major hepatic or pancreatic surgery with complications (cases) and without complications (controls). The files are in FASTQ format.

  Dataset EGAD00001008317

• Genetic drivers of epigenetic and transcriptional variation of human immune responses to infection (WGS and WGBS)

  WGS and WGBS data from monocyte-derived macrophages that were infected with Influenza A virus strain PR8WT, or a matching non-infected control.

  Dataset EGAD00001008359

• Genetic drivers of epigenetic and transcriptional variation of human immune responses to infection (RNA-seq, ATAC-seq and ChIPmentation)

  RNA-seq, ATAC-seq and ChIPmentation data from monocyte-derived macrophages that were infected with Influenza A virus strain PR8WT, or a matching non-infected control.

  Dataset EGAD00001008422

• Epigenetic, transcriptome and TF analysis of human NK cell and T cells

  RNA-seq 10 subsets; 5 donors. ATAC-seq 9 subsets, 4 donors; Histone modification profiling 10 subsets, 2 donors all using human NK cell and T cell subsets. TF ChIP-seq Bcl11b, Bach2, Runx2, Gata3, PLZF. Illuminia sequencing platform, ATAC-seq is Paired-end, RNA-seq/ChIP-seq is Single-end

  Dataset EGAD00001008449

• COVID-19 Severity First Wave of Infection for Severe Patients in Madrid

  We recruited 98 hospitalised patients displaying severe COVID-19 symptoms from the first wave of infection. A stringent exclusion criteria based on non-genetic factors such as age, blood oxygen, radiologic findings and other typical COVID-19 signs was performed. Gingival or peripheral blood samples were taken for 98 individuals and whole exome sequencing performed using ExomeCapture-Seq capture KAPA HyperExome on Illumina machines.

  Dataset EGAD00001008464

• Single-Cell Atlas of Common Variable Immunodeficiency shows germinal center-associated epigenetic dysregulation in B cell responses

  Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency. Here the authors perform single cell omics analyses in CVID discordant monozygotic twins and show epigenetic and transcriptional alterations associated with activation in memory B cells.

  Dataset EGAD00001008575

• Enhancer profiling to identify identifies epigenetic markers of endocrine resistance in metastatic castration resistant prostate cancer patients

  ChIP-seq and matched input data of AR, FOXA1 and H3K27ac for mCRPC patient samples taken prior to and after treatment with AR targeted therapy

  Dataset EGAD00001008688

• Mixture of 4

  Mixture of 4 unrelated individuals sequenced by 10x as a scRNA-seq. The dataset was then processed by Cell Ranger and deconvoluted to yield each individuals genetic profile. The clustering of SNPs is submitted as the processed file. The Sequencing fastqs are submitted as unprocessed files.

  Dataset EGAD00001008724

• Mixture of 2

  Mixture of 2 unrelated individuals sequenced by 10x as a scRNA-seq. The dataset was then processed by Cell Ranger and deconvoluted to yield each individuals genetic profile. The clustering of SNPs is submitted as the processed file. The Sequencing fastqs are submitted as unprocessed files.

  Dataset EGAD00001008726

• Mixture of 2 (closer mtDNA)

  Mixture of 2 unrelated individuals (of close mtDNA haplogroup) sequenced by 10x as a scRNA-seq. The dataset was then processed by Cell Ranger and deconvoluted to yield each individuals genetic profile. The clustering of SNPs is submitted as the processed file. The Sequencing fastqs are submitted as unprocessed files.

  Dataset EGAD00001008727

• Mixture of 3

  Mixture of 3 unrelated individuals sequenced by 10x as a scRNA-seq. The dataset was then processed by Cell Ranger and deconvoluted to yield each individuals genetic profile. The clustering of SNPs is submitted as the processed file. The Sequencing fastqs are submitted as unprocessed files.

  Dataset EGAD00001008729

• Salivary Gland Cancer TSO500 dataset

  DNA was extracted from archival tissue of 119 patients with various SGC subtypes and sequenced using a targeted NGS panel encompassing 523 cancer related genes (TruSight Oncology 500, TSO500). This dataset belongs to the publication entitled: 'Identification of fusion genes and targets for genetically matched therapies in a large cohort of salivary gland cancer patients'.

  Dataset EGAD00001008759

• MBL2 genetic variation in critical Covid-19

  The data set includes MBL2 genotypes and clinical phenotypes of a cohort of patients with critical Covid-19. The files included in the data set include a vcf file with single nucleotide variants, and a file with clinical phenotypes.

  Dataset EGAD00001008771

• ALI transcripomics microarray data

  Gene transcript data from ALI-cultured airway cells, acquired using microarrays.

  Dataset EGAD00010002377

• Exome Sequencing of 44 subjects with very severe or fatal COVID-19

  In this study, the DNA of 44 subjects with severe COVID-19 have been sequenced in order to explore rare genetic variants.

  Dataset EGAD00001008993

• HSP90 inhibitor resistant K562 cells

  K562 cell line has been treated with two different HSP90 inhibtors. After resistance clones emerged, they have been genetically characterized using WES in comparison to the parental K562 cell line.

  Dataset EGAD00001009051

• Convergent somatic evolution from early life in a germline ribosomopathy

  Clonal tracking of stem cells and their progeny by whole genome sequencing permits exploration of evolutionary genetics in human disease. In this study, we performed phylogenetic reconstruction of haematopoiesis using somatically acquired mutations in 323 single haematopoietic stem and progenitor cell-derived colonies from 10 individuals with an inherited disorder of ribosome assembly, Shwachman-Diamond syndrome. We observed numerous clonal expansions, with recurrent acquisition of mutually exclusive mutations (EIF6, TP53, RPL5, RPL22, PRPF8, chromosomes 7 and 15) in multiple different clones in utero or early childhood converging on the p53-dependent nucleolar surveillance pathway that monitors ribosome integrity. In contrast to clones carrying biallelic TP53 mutations, genomes derived from colonies carrying mono-allelic TP53 mutations displayed no increase in mutation burden or specific mutational signatures. Our study highlights striking loss of clonal diversity with convergent somatic evolution on the p53-dependent nucleolar surveillance pathway from early life to offset the deleterious effects of a germline mutation in a Mendelian haematopoietic disorder.

  Dataset EGAD00001009061

• Genetic regulation of RNA splicing in human pancreatic islets

  Here we provide access to newly generated RNA-seq data for 101 human islet samples used to map genetic effects on gene expression and alternative splicing (eQTLs and sQTLs) in a total of 399 human islets. We also make publicly available genotyping array data for 128 human islets, including the fraction of 101 human islet samples with existing RNA-seq data.

  Dataset EGAD00001009102

• Clonal origin of lineage switch leukemia following CAR-T cell and blinatumomab therapy

  Children with ALL treated with anti-CD19 therapy occasionally develop a phenotypically distinct AML. However, the precise clonal origin of such class switch leukemias remains unresolved. Here, we reconstructed the evolution of leukemia in a child with primary ALL, two ALL relapses and AML after treatment with anti-CD19 CAR-T and blinatumomab through whole-genome sequencing. The phylogeny revealed that the AML was a monoclonal outgrowth descending from the initial ALL and harbored biallelic loss of CDKN2A, PAX5 and TP53. However, none of the ALL or AML relapses directly descended from one another, suggesting the presence of a reservoir of persistent clones. Our findings suggest anti-CD19 treatment selects pre-existing clones, with many key genetic alterations underpinning the lineage switch detectable prior to treatment.

  Dataset EGAD00001009161

• Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia - RNA

  Genomic profiling at diagnosis of B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL) in adults is used to guide disease classification, risk stratification and treatment decisions. Patients for which diagnostic screening fails to identify disease defining or risk stratifying lesions are classified as B-other ALL. We screened a cohort of 652 BCP-ALL cases enrolled in UKALL14 to identify and perform whole genome sequencing (WGS) on paired tumor-normal samples. For 52 B-other patients we compared WGS findings to data from clinical and research cytogenetics. WGS identifies a cancer associated event in 51/52 cases, this includes an established subtype defining genetic alteration in 5/52 that were previously missed by standard-of-care genetics. Of the 47 true B-other ALL we identified a recurrent driver in 87% (41).  Complex karyotype by cytogenetics emerges as a heterogeneous group, underlied by distinct genetic alterations associated with either favorable (DUX4-r) or poor outcomes (MEF2D-r, IGK::BCL2). For a subset of 31 cases, we integrate findings from RNA-sequencing (RNA-seq) analysis to include fusion gene detection, and classification by gene expression. Compared to RNA-seq, WGS was sufficient to detect and resolve recurrent genetic subtypes, however RNA-seq can provide orthogonal validation of findings. In conclusion, we demonstrate that WGS can identify clinically relevant genetic abnormalities missed by standard-of-care testing and identify leukemia driver events in virtually all cases of B-other ALL.

  Dataset EGAD00001009305

• Diagnostic utility of whole genome sequencing in adults with B-other acute lymphoblastic leukemia

  Genomic profiling at diagnosis of B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL) in adults is used to guide disease classification, risk stratification and treatment decisions. Patients for which diagnostic screening fails to identify disease defining or risk stratifying lesions are classified as B-other ALL. We screened a cohort of 652 BCP-ALL cases enrolled in UKALL14 to identify and perform whole genome sequencing (WGS) on paired tumor-normal samples. For 52 B-other patients we compared WGS findings to data from clinical and research cytogenetics. WGS identifies a cancer associated event in 51/52 cases, this includes an established subtype defining genetic alteration in 5/52 that were previously missed by standard-of-care genetics. Of the 47 true B-other ALL we identified a recurrent driver in 87% (41).  Complex karyotype by cytogenetics emerges as a heterogeneous group, underlied by distinct genetic alterations associated with either favorable (DUX4-r) or poor outcomes (MEF2D-r, IGK::BCL2). For a subset of 31 cases, we integrate findings from RNA-sequencing (RNA-seq) analysis to include fusion gene detection, and classification by gene expression. Compared to RNA-seq, WGS was sufficient to detect and resolve recurrent genetic subtypes, however RNA-seq can provide orthogonal validation of findings. In conclusion, we demonstrate that WGS can identify clinically relevant genetic abnormalities missed by standard-of-care testing and identify leukemia driver events in virtually all cases of B-other ALL.

  Dataset EGAD00001009304

• Single-cell omics data for COVID-19 patients

  Single-cell RNA-seq, single-cell ATAC-seq, and genotypes used in the analysis for the study "Altered and allele-specific open chromatin landscape reveal epigenetic and genetic regulators of innate immunity in COVID-19". The RNA-seq and ATAC-seq are raw data in FASTQ format while the genotypes are in the VCF format which was filtered and imputed (more details are available in the main text of the study).

  Dataset EGAD00001009331

• Cancers of Unknow Primary

  genetic data of 14 rigorously selected CUP samples

  Dataset EGAD00001009426

• Tracking the evolution of esophageal squamous cell carcinoma under dynamic immune selection by multi-omics sequencing

  Intratumoral heterogeneity (ITH) has been linked to decreased efficacy of clinical treatments. However, although genomic ITH has been characterized in genetic, transcriptomic and epigenetic alterations are hallmarks of esophageal squamous cell carcinoma (ESCC), the extent to which these are heterogeneous in ESCC has not been explored in a unified framework. Further, the extent to which tumor-infiltrated T lymphocytes (TILs) are directed against cancer cells, but how the immune infiltration acts as a selective force to shape the clonal evolution of ESCC is unclear. In this study, we perform multi-omic sequencing on 186 samples from 36 primary ESCC patients. Through multi-omics analyses, it is discovered that genomic, epigenomic, and transcriptomic ITH are underpinned by ongoing chromosomal instability. Based on the RNA-seq data, we observe diverse levels of immune infiltrate across different tumor sites from the same tumor. We reveal genetic mechanisms of neoantigen evasion under distinct selection pressure from the diverse immune microenvironment. Overall, our work offers an avenue of dissecting the complex contribution of the multi-omics level to the ITH in ESCC and thereby enhances the development of clinical therapy.

  Dataset EGAD00001009482

• Follicular lymphoma at diagnosis, treated in first line with immunochemotherapy

  We performed targeted NGS in Follicular lymphoma samples at diagnosis. Explored clinico-genetic correlations and assessed four clinical or clinicogenetic risk models (FLIPI, FLIPI-2, PRIMA-IP or m7-FLIPI-molecular score) in patients with symptomatic FL who received frontline immunochemotherapy. Out of 191 patients with FL grade 1-3a, 109 were successfully genotyped. Treatment consisted on rituximab (R) plus CVP/CHOP (72.5%) or R-bendamustine (R-B) (27.5%).

  Dataset EGAD00001009647

• DNA methylation-based classification of sinonasal tumors [DNA sequencing]

  This dataset contains raw exome sequencing data from nine sinonasal undifferentiated carcinoma FFPE samples and matched normal tissue that were assigned to a shared epigenetic class using DNA methylation-based classification. They were analyzed using the Twist Human Core Exome Plus Kit (Twist Bioscience) on a NovaSeq 6000 sequencer.

  Dataset EGAD00001009668

• RNAseq data

  RNAseq FASTq files from 797 tumors from AVANT. Sequencing libraries were generated with the TruSeq Stranded Total RNA kit (Illumina) following ribosomal RNA (rRNA) depletion with the Ribo-Zero Gold kit (Illumina). The libraries were sequenced on the HiSeq4000 (Illumina) with a sequencing protocol of 75 bp paired-end sequencing. Note: 10 samples used in the original publication were excluded from this upload due to regulations from the Human Genetics Resources Administration of China (HGRAC).

  Dataset EGAD00001009728

• HELIUS cohort gut microbiome batch2

  The gut microbiota composition is unique to every individual but is shaped by common factors including diet, lifestyle, medication use, early-life determinants, living environment or genetics. Most of these factors may be influenced by ethnicity. This study explored variations in fecal microbiota composition in 6048 individuals with different ethnic backgrounds living in the same geographical area (Amsterdam, the Netherlands). The HELIUS data are owned by the Amsterdam University Medical Centers, location AMC in Amsterdam, The Netherlands. To allow sharing of microbiome data collected in HELIUS with (inter)national researchers, 16s rRNA sequence analysis has been stored at the European genome-phenome archive (EGA; accession code EGAD00001004106). This requires that access needs to be granted, also because the HELIUS data are stored with relevant phenotypical variables. Access is granted to all researchers affiliated with an internationally recognized research institution who request to use the HELIUS data within the EGA context, after having signed the data transfer agreement. Any researcher can request the data by submitting a proposal to the HELIUS Executive Board as outlined at http://www.heliusstudy.nl/en/researchers/collaboration, by email: heliuscoordinator at amsterdamumc dot nl. The HELIUS Executive Board will check proposals if they do not conflict with ethical approvals and informed consent forms of the HELIUS study.

  Dataset EGAD00001009732

• Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities - WGS

  We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles

  Dataset EGAD00001009793

• Atypical teratoid/rhabdoid tumoroids reveal subgroup-specific drug vulnerabilities - RNA-Seq

  We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles

  Dataset EGAD00001009794

• DNA-Methylation data for atypical teratoid/rhabdoid tumoroids study

  We demonstrate that ATRT tumoroids retain subgroup-specific epigenetic and gene expression profiles

  Dataset EGAD00010002400

• Single-cell study of 14 childhood medulloblastoma patients

  Medulloblastoma intra-tumoural genetic heterogeneity and clonal evolution, and their role in disease pathogenesis and clinical behaviour, are poorly understood. We used single-cell whole-genome sequencing (sc-WGS) to reconstruct the natural history and temporal evolution of 14 medulloblastomas, representing its major clinico-molecular sub-classes. We identified wholly-clonal tumours which displayed single-clone expansion (i.e. linear evolution); all were observed in favourable-outcome sub-classes (i.e. MBWNT and infant MBSHH). In contrast, remaining tumours harboured sub-clonal structures which displayed punctuated or gradual trajectories; highest-risk sub-classes, typically characterised by MYC-amplification (MBGroup3) or TP53-mutation (MBSHH), and linked to genomic instability and LCA pathology, were most clonally-diverse. Clinically-adopted biomarkers were typically early-clonal/initiating events, representing exploitable targets for early-disease detection; in analyses of spatially-distinct tumour regions, a single biopsy was sufficient to assess their status. sc-WGS revealed events not previously appreciated in bulk tumour analysis, which arose later and/or sub-clonally and more commonly displayed spatial diversity; their clinical significance and role in disease evolution post-diagnosis now require establishment. In summary, our findings reveal diverse modes of tumour initiation and clonal evolution in the major medulloblastoma sub-classes, highlighting their pathogenic relevance and clinical potential.

  Dataset EGAD00001009057

• Population-based analysis of POT1 variants in a cutaneous melanoma case-control cohort

  Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumor types, including melanoma, glioma, leukemia and cardioangiosarcoma. We sequenced all coding exons of the POT1 gene in 2,929 European-descent melanoma cases and 3,298 controls, identifying 43 protein-changing genetic variants. We performed functional studies on each of these variants and explored their possible contribution to disease risk.

  Dataset EGAD00001009848

• Genomic Analysis of a Metastatic Fusion-negative Embryonal Rhabdomyosarcoma

  Autopsy-derived, later snap-frozen tissue fragments from a 5-year-old female with recurrent metastatic fusion-negative embryonal rhabdomyosarcoma (RMS) primary tumor of the left thigh were analyzed. No quality matched tissue was available. Prior panel analysis identified 2 prominent genetic changes: NRAS Q61K, PIK3CA H1047R, CDKN2A/B loss, and ERBB3 overexpression.

  Dataset EGAD00001009973

• Clonal dynamics after allogeneic haematopoietic cell transplantation using genome-wide somatic mutations - WGS

  Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those harvested from a donor, and is received by 40,000 patients worldwide each year. To quantify dynamics of long-term stem cell engraftment, we sequenced whole genomes of 2,824 single-cell-derived haematopoietic colonies from blood samples of 10 donor-recipient pairs taken 9-31 years after HLA-matched sibling HCT. With younger donors, 10,000-50,000 stem cells had engrafted and were still contributing to haematopoiesis at time of sampling, but estimates were 10-fold lower with older donors. Engrafted stem cells made multilineage contributions to myeloid, B-lymphoid and T-lymphoid populations, although individual clones often showed biases towards one or other mature cell type. Recipients had lower clonal diversity than matched donors, equivalent to ~10-15 years of additional ageing, arising from up to 25-fold greater expansion of stem cell clones. An HCT-related population bottleneck alone could not explain these differences: instead, phylogenetic trees evinced two distinct modes of HCT-specific selection. In 'pruning selection', cell divisions underpinning recipient-enriched clonal expansions had occurred in the donor, preceding transplant - their selective advantage derived from preferential mobilisation, harvest, survival ex vivo or initial homing. In 'growth selection', cell divisions underpinning clonal expansion occurred through proliferative advantage in the recipient's marrow after homing - clones with multiple driver mutations especially demonstrated this pattern. Uprooting stem cells from their native environment and transplanting them to foreign soil exaggerates selective pressures, distorting and accelerating the loss of clonal diversity compared to the unperturbed haematopoiesis of donors.

  Dataset EGAD00001010872

• Clonal selection after gene therapy in sickle cell disease

  While gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD), the occurrence of myeloid malignancies in clinical trials has prompted concern. To interrogate potential mechanisms underlying increased cancer risk, we used hematopoietic stem cell (HSC) clonal tracking by whole genome sequencing (WGS) to map the somatic mutation and clonal landscape of 2,592 gene modified as well as unmodified single stem and progenitor cells from six SCD patients undergoing gene therapy (7-26 years old, average 12.7× depth). Pre-GT phylogenetic trees in SCD were highly polyclonal and mutation burdens per cell were elevated in some, but not all, patients. Post-GT, no clonal expansions were identified. However, an increased frequency of driver mutations associated with myeloid neoplasms or clonal hematopoiesis (DNMT3A- and EZH2-mutated clones in particular) were seen in both genetically modified and unmodified cells suggested positive selection of mutant clones during gene therapy. This work sheds light on the mutation landscape and HSC clonal dynamics in gene therapy for SCD and highlights enhanced fitness of some HSCs harboring pre-existing driver mutations following gene therapy. Future studies should define the long-term fate of mutant clones including any contribution to expansions associated with myeloid neoplasms.

  Dataset EGAD00001010914

• Genomic and transcriptomic data of glioma specimens

  Dataset consists of 207 glioma samples of WHO grades II, III and IV. Dataset consists 182 tumor derived genomic data of ~700 cancer-related and epigenetic-related genes with matched blood samples for 48 specimens. Dataset also consists transcriptomic data for 105 specimens. In total 335 bam files were deposited.

  Dataset EGAD00001006299

• The Natural History of Human Prostate Cancer

  Whole genome DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of 3 men. For each of three different prostates, multiple tumour samples (4, 5, and 3 depending on the case) and one normal tissue sample were whole genome sequenced with a matched blood sample using the Illumiuna HiSeq platform. Tumour samples were sequenced to a target depth of 50X and normals and blood to a target depth of 30X. As of September 2020, some of the studies using these data include: Cooper et al, Nature Genetics 2015 (PMID: 25730763) Wedge et al, Nature Genetics 2018 (PMID: 29662167) Pan-Cancer Analysis of Whole Genomes, Nature 2020 (PMID: 32025007)

  Dataset EGAD00001000689

• Batches 1-3 prostatectomy analysis

  Whole Genome Sequencing Illumina HiSeq data from 95 men with prostate cancer. Samples were taken from primary tissue obtained at prostatectomy (target sequencing depth 50X) with matched blood control (target sequencing depth 30X). This data is from batches 1 to 3 and is the bulk of the data used in Wedge et al, Nature Genetics 2018 (PMID: 29662167). As of September 2020, some of the studies using these data include: Wedge et al, Nature Genetics 2018 (PMID: 29662167) Pan-Cancer Analysis of Whole Genomes, Nature 2020 (PMID: 32025007)

  Dataset EGAD00001001116

• Determination of cell specific regulatory enhancers in hematopoetic models

  The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The human variation workpackage (WP10, led by NS) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise "experimental noise" and therefore enhance the power to discover modest effects. Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose. The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively. Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers. Units of 475 ml of AB will be obtained from consenting volunteers of the Cambridge BioResource (CBR), a panel of 10,000 healthy volunteers local to Cambridge who have already consented to participate in biomedical research and of whom biological samples (DNA, plasma, serum) and lifestyle data have been deposited in a repository and database, respectively. We are requesting funding from the Human Diversity project to sequence the genomes of the 200 CBR volunteers at low pass (6x coverage). Nuclei, DNA and RNA will be recovered from the purified cells and made available for RNA-seq, DNA-seq and ChIP-seq and genomic DNA for entire genome sequencing will be recovered from the DNA repository.

  Dataset EGAD00001002205

• Sequencing data for ICGC Oesophageal Adenocarcinoma tissue samples - 129_cohort

  Sequencing data for ICGC Oesophageal Adenocarcinoma tissue samples - 129_cohort EAC whole genomic sequencing data - Publication Secrier & Li et al., 2016, Nature Genetics

  Dataset EGAD00001002218

• BLUEPRINT EpiVar ChIP-seq in lineage specifying transcription factors

  The BLUEPRINT project is a large-scale project investigating epigenetic mechanisms involved in blood formation, in health and disease. The human variation workpackage (WP10) of the project seeks to characterize the effect of common sequence variation on the epigenome status of a cell. To do this, the project will use highly purified blood cells to minimise "experimental noise" and therefore enhance the power to discover modest effects. Two peripheral blood cell types, the CD14+CD16- monocyte (an important central orchestrator of adaptive immunity and a bridge between innate and adaptive immunity) and the CD65+CD9- neutrophilic granulocyte (the frontline cell for innate immunity) have been selected for this purpose. The two types of cells will be obtained at high purity from adult blood (AB) of 200 healthy males and females, respectively. Cells will be purified by using already validated and fully operational protocols that are based on density gradient centrifugation of the buffy coat obtained from whole blood, followed by magnetic bead-based purification using monoclonal antibodies against Cluster of Differentiation (CD) lineage-specific cell surface markers. This data set contains functional genomics data for gene expression and chromatin state.

  Dataset EGAD00001004571

• Cell of Origin and Early Evolution of Leukemia in Down Syndrome

  To investigate the mechanism by which GATA1s and STAG2 deficiency contribute to Down Syndrome leukemogenesis, specifically within the propagating CD34/CD117 cell fractions from primary xenografts, we carried out transcriptional and epigenetic profiling by RNAseq and ATACseq. The chromatin accessibility landscape was compared to bulk ATACseq of individually sorted N-FL HSPC subpopulations. To investigate the mechanism underlying the synergy between T21 and GATA1s in driving preleukemia development, we analyzed the binding occupancy of GATA1. We performed Cut&Run assays to profile genome-wide GATA1 binding sites and also to quantify binding changes upon GATA1s editing in N-FL and T21-FL CD34+ enriched HSPCs. Lastly, we profiled miRNAs from N-FL and T21-FL CD34+ enriched HSPCs by miRNA-Seq.

  Dataset EGAD00001006555

• DDD_1 hypermutated individual

  CRAM files and VCF for DDD_1 and their parents. Also de novo mutations file for hypermutated DDD_1 child as described in the manuscript ‘Genetic and chemotherapeutic influences of germline hypermutation’ by Kaplanis et al. which will be published in Nature shortly.

  Dataset EGAD00001008497