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• Deep sequencing of S7EPC genome

  PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation. The library will be sequenced either by HiSeq or MiSeq. 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 EGAD00001000607

• Subclonal analysis in S7RE2 and S7RE14 iPS cells

  PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation. The library will be sequenced either by HiSeq or MiSeq. 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 EGAD00001000608

• Validation of SNVs found by Exome-seq in S2-SF1, -SF5 and -SF9 hiPSCs

  PCR products were obtained from each target loci using genomic DNA from human iPS cells. Subsequently, PCR products are pooled and subjected to Illumina library preparation. The library will be sequenced either by HiSeq or MiSeq. 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 EGAD00001000631

• Long-read whole-genome sequencing-based concurrent haplotype phasing and aneuploidy profiling of single cells

  This dataset contains long-read whole-genome sequencing (lrWGS) data from 14 samples. Five lrWGS data are from single-cell (sc, sc_2, sc_3), multi-cell (mc, 10 cells), and bulk samples of HG002. The remaining nine lrWGS data are from two preimplantation genetic testing (PGT) families, including four from blood bulk DNA of the parental pairs and five from trophectoderm biopsies of two embryos from one family and three embryos from another family. The data are provided in raw FASTQ format and were generated using the PromethION device from Oxford Nanopore Technologies.

  Dataset EGAD50000000787

• Circular RNA characterization in functionally distinct brain regions

  Circular RNAs (circRNAs) represent a class of endogenous, non-coding RNAs that are formed when exons back splice to each other and that are both highly conserved and pervasively expressed in the mammalian brain. The goal of this study was thus to systematically identify and characterize circRNA expression and as well as to evaluate the predicted impact on regulatory networks in five functionally distinct cortical regions of healthy aged human brain - cerebellum (BC), inferior parietal lobe (IPL), middle temporal gyrus (MTG), occipital cortex (OC) and superior frontal gyrus (SGF).

  Study EGAS00001003128

• Nuclear_single_seq_pilot

  The aim of this study is to analyse the genomes of tumours

  Study EGAS00001003386

• BPH Tissues for Cell Culture and Analysis - Spatial Transcriptomics Identifies Candidate Stromal Drivers of Benign Prostatic Hyperplasia

  The study goal was to apply spatial transcriptomics to identify candidate stromal drivers of benign prostatic hyperplasia (BPH). Laser microdissection (LCM) with RNA-seq of the stroma adjacent to hyperplastic and budding BPH ducts identified secreted factors including IGF1 and CXCL13. Single‐cell RNA sequencing (scRNA‐seq) revealed their co-expression from BPH fibroblasts. Additional studies sought to define similarities to embryonic prostate development, as well as therapeutic applications. Subjects were those who underwent prostatectomy for prostate or bladder cancer, with concurrent BPH, and who consented to use of surplus tissue for research studies. LCM/RNA-seq studies included 5 patients, and scRNA-seq studies included 1 patient. Phenotypic data submitted to this study include patient age, sex, prostate size, and international prostate symptom score (IPSS). Sequencing was done on an Illumina NovaSeq 6000 (LCM/RNAseq) and Illumina HiSeq X-Ten (scRNA-seq). The data processing pipeline utilized Kallisto (LCM/RNA-seq) and Cell Ranger (scRNA-seq). Data submitted are raw sequencing (Fastq) files.

  Study phs003477

• Differential methylation positions

  This dataset includes an analyzed DMP file that provide the information about differential methylation positions based on Illumina Infinium MethylationEPIC BeadChip. All samples (5 lung cancer cases vs. 5 benign lung disease controls) were obtained from bronchial washings at the site of the lesion under bronchoscopy manipulation. Of the five lung cancer cases, 3 are adenocarcinoma and 2 are squamous carcinoma.

  Dataset EGAD00001010147

• Targeted panel data for newly diagnosed myeloma patients.

  Genomic abnormalities in MM are common and can affect a patients outcome. Here we have performed targeted sequencing on xx patient tumor samples and matched control DNA. The targeted panel consists of ~160 genes and copy number regions, as well as key regions of chromosomal translocation including IGH, IGK, IGL and MYC. Using mutation, copy number, and translocation information we have been able to identify abnormalities that affect prognosis including bi-allelic inactivation of TP53 and rearrangements involving MYC.

  Study EGAS00001002859

• Garvan/St Vincent’s Prostate Cancer Tissue and Data

  The cohort (n=53) consists of prostate cancer patients from Australia. For each patient, a pair of blood and tumour samples were collected. The sequencing data was mapped to hg38 reference. Blood BAMs are named with “-B” as suffix and tumour BAMs are named with “-T” as suffix.

  Dataset EGAD00001009066

• Nanobody-Tethered Transposition Allows for Multifactorial Chromatin Profiling at Single-Cell Resolution

  Chromatin states are functionally defined by a complex combination of histone modifications, transcription factor binding, DNA accessibility, and other factors. However, most current single-cell-resolution methods are unable to measure more than one aspect of chromatin state in a single experiment, limiting our ability to accurately measure chromatin states. Here we introduce nanobody-tethered transposition followed by sequencing (NTT-seq), a new assay capable of measuring the genome-wide presence of multiple histone modifications and protein-DNA binding sites at single-cell resolution. NTT-seq utilizes recombinant Tn5 transposase fused to a set of secondary nanobodies (nb). Each nb-Tn5 fusion protein specifically binds to different immunoglobulin-G antibodies, enabling a mixture of primary antibodies binding different epitopes to be used in a single experiment. We apply bulk- and single-cell NTT-seq to generate high-resolution multimodal maps of chromatin states in cell culture and cells of the human immune system, demonstrating the high accuracy and sensitivity of the method. We further extend NTT-seq to enable simultaneous profiling of cell-surface protein expression alongside multimodal chromatin states to study cells of the immune system.

  Study phs003068

• Direct Detection of Early-stage Cancers Using Circulating Tumor DNA

  Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.

  Study EGAS00001002577

• Integrative Analysis for Multi-Omics Data in Non-Small-Cell Lung Cancer

  We conducted epigenetic and transcriptomic mapping of primary non-small cell lung tumors and non-neoplastic tissues. 20 non-neoplastic lung tissues and 18 non-small cell lung tumors were obtained from Biorepository and Tissue Technology Shared Resource at Moores Cancer Center, UC San Diego. All tumor samples were in pathological stages I and II. 8 pairs of samples were "matched", meaning that the tumor and normal tissues came from the same patient. Microfluidic oscillatory washing–based chromatin immunoprecipitation followed by sequencing (MOWChIP-seq) was used to profile the binding of H3K4me1, H3K4me3, H3K9me3, H3K27ac and H3K27me3. SmartSeq-2 was used to map mRNA expression. We identified a large number of differentially modified regions for both epigenetic and transcriptomic markers between tumors and normal tissues. Deep learning model showed extensive transcription factor network rewiring. Raw sequencing data of the ChIP-seq and RNA-seq libraries are available through this dbGaP submission.

  Study phs003113

• Coverage bias and sensitivity of variant calling for four whole-genome sequencing technologies

  Massively parallel sequencing has revolutionized research in cancer genetics and genomics and enhanced our understanding of natural human genetic variation. Recently, Lam et al. have performed a detailed comparison of two next-generation sequencing technologies with respect to their sensitivity to call single nucleotide variants (SNV) and indels. Here, we sequenced two tumor/normal pairs obtained from two paedriatic medulloblastoma patients with Life Technologies’ SOLiD 4 and 5500xl SOLiD, Illumina’s HiSeq2000, and Complete Genomics’ technology. We then compared their ability to call SNVs with high confidence. As gold standard for SNV calling, we used genotypes determined by an Affymetrix SNP array. Additionally, we performed a detailed analysis of how evenly each technology covers the genome and how the reads are distributed across functional genomic regions. Finally, we studied how a combination of data from different technologies might help to overcome the limitations in SNV calling by any of the four technologies alone.

  Study EGAS00001000274

• Discovering novel mechanisms of taxane resistance in human breast cancer by whole-exome sequencing

  Taxanes are key drugs in the treatment of breast cancer, but some breast cancers are resistant to taxanes. Obtaining extensive genomic information in a short time has recently become possible. We used whole exome-sequencing (WES) to investigate mechanisms of taxane resistance in human breast cancer. We selected six patients with breast cancer whose tumors responded well to anthracycline treatment but grew rapidly during neoadjuvant taxane-based chemotherapy. We then performed WES of these samples and identified somatic mutations of candidate genes that are thought to affect taxane resistance.

  Study JGAS000370

• Reconstruction of complex rearrangement patterns causing the initiation of clear cell renal cell carcinoma.

  The genomic hallmark of clear cell renal cell carcinoma is the loss of the short arm of chromosome three. This appears to be the earliest genomic event in the formation of these cancers. Often chromosome 3 is lost at the same time as part of chromosome 5 is duplicated via an unbalanced translocation, often with features consistent with focal chromothripsis. In this study, we sought to reconstruct the chromothriptic event that underlies the initiation of kidney cancer. We used long read sequencing (promethION, Oxford Nanopore Technologies) of patient tumour-derived DNA to elucidate how a single cell division error can generate cancer genome complexity.

  Study EGAS00001004015

• WGBS files for PCGP NBL_MYCN_ATRX

  WGBS files for PCGP NBL_MYCN_ATRX paper titled "MYCN Amplification and ATRX Mutations are Incompatible in Neuroblastoma"

  Dataset EGAD00001004559

• Genome-Wide Association Studies in Upper Gastrointestinal Cancers (Asian)

  This project aims to conduct genome-wide association studies (GWAS) in two anatomically different upper gastrointestinal (UGI) cancer sites in two populations with distinctly different disease rates and genetic profiles. One population has very high rates for both esophageal squamous cell carcinomas (ESCCs) and gastric cancers (GCs) and is comprised of Asians (the "Asian UGI GWAS"), while the other population has low rates of ESCC and GC and includes non-Asians from the Americas, Europe, and Australia (the "Non-Asian UGI GWAS"). Study participants for the Asian UGI GWAS reported here (Illumina 660W Quad chip) were drawn from 2 studies, the Shanxi Upper Gastrointestinal Cancer Genetics Project (Shanxi) and the Linxian Nutrition Intervention Trial (NIT), a prospective cohort, and included a total of 1898 ESCCs, 1625 GCs, and 2100 controls. For the 2nd phase (8 TaqMan SNPs), additional subjects from Shanxi and NIT as well as subjects from the Shanghai Men's Health Study (SMHS), the Shanghai Women's Health Study (SWHS), and the Singapore Chinese Health Study (SCHS) were also included (217 ESCCs, 615 GCs, 1202 controls). Altogether 2115 ESCCs, 2240 GCs, and 3302 controls were genotyped in this study.

  Study phs000361

• SNPs and Extent of Atherosclerosis (SEA) Study

  The SEA study is a genome-wide association study to identify genetic variants associated with premature atherosclerosis in subjects included in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) repository - a unique NHLBI resource including data, DNA and arterial specimens from over 3000 multi-ethnic subjects 15-34 years of age who died of non-atherosclerotic causes (mostly trauma). All PDAY subjects had post-mortem quantitative assessment of raised atherosclerotic lesions in their aorta and coronary arteries - making this the largest and most carefully phenotyped cohort for premature atherosclerosis in the world. The goal of the current project was to use the quantitative measure of raised atherosclerotic lesions in the PDAY cohort as the target phenotype for a genome-wide association study and to use quantitative measures of subclinical atherosclerosis (coronary calcium and carotid IMT) in the Multi-Ethnic Study of Atherosclerosis (MESA) to confirm or refute candidate loci identified from the PDAY analysis. Identifying genetic factors that predispose individuals to premature atherosclerosis could lead to more effective screening and early treatment of high risk individuals and suggest novel molecular targets for treatment and prevention interventions.

  Study phs000349

• Germline

  This study is part of the 'First 1,000 Days of Life and Beyond' study at the Inova Translational Medicine Institute. Whole-genome sequencing data from 1,291 parent-offspring trios was used to study the properties of clustered de novo mutations. The maternal clusters were found to be enriched in regions with accelerated maternal mutation rate and show distinct mutational signatures. For additional details, please refer to: "Germline de novo mutation clusters arise during oocyte aging in genomic regions with increased double-strand break incidence". Jakob M. Goldmann, Vladimir B. Seplyarskiy, Wendy S.W. Wong, Thierry Vilboux, Pieter B. Neerincx, Dale L. Bodian, Benjamin D. Solomon, Joris A. Veltman, John F. Deeken, Christian Gilissen, John E. Niederhuber. Nature Genetics.

  Study phs001522

• Genome Wide Association Study of Serum Creatinine during Vancomycin Therapy and Vancomycin Pharmacokinetics

  The goal of this study was to identify genetic variants associated with risk for acute kidney injury (AKI) in patients being treated with vancomycin and genetic variants associated with variability in vancomycin pharmacokinetics. AKI is a common adverse drug event and known complication of vancomycin therapy. Known risk factors fail to accurately predict renal toxicity. Our hypothesis, that genetic variants modify the risk of AKI, was tested by performing genome-wide association and linear regression in 429 patients of European descent using the outcome of peak serum creatinine while on vancomycin. We also tested the hypothesis that genetic variants associate with vancomycin pharmacokinetics, using vancomycin trough levels and calculated renal elimination rate constant as outcomes.

  Study phs000894

• Long-read whole genome sequencing of gastric cancer

  Gastric cancer (GC) remains a significant health challenge globally, with a particularly high incidence in Asia, including Singapore. Understanding the genomic landscape of normal gastric and the different GC subtypes along with its precursor lesions such as intestinal metaplasia (IM) as well as GC metastatic sites is crucial for advancing diagnostics, prognostics, and therapeutics. Long-read sequencing technologies offer an opportunity to delve deeper into the genomic and epigenetic alterations underlying these conditions and to complement existing short-read omics data. By integrating these data with previously generated in-house multi-omics data (such as RNA sequencing and whole exome sequencing), we hope to better elucidate the molecular mechanism underlying GC initiation and progression.

  Study EGAS50000001607

• Guardians_of_the_genome__protecting_DNA_from_endogenous_sources_of_damage_

  Analysis of mutational signatures caused by DNA repair defects in human induced pluripotent stem (iPS) cells. A reference human iPS cell line will be used for genetic manipulation to introduce homozygous knockouts of 100 genes known to be involved in or connected to DNA repair or DNA editing. Following a defined period of growth after homozygous knockout of each gene, sub clones will be generated and sequenced. The progenitor “parental” IPS cell line will be used to generate reference sequence data, in order to determine the mutational signature acquired due to the gene knockout. This is a pilot study to investigate the effects of oxygen conditions and growth period on mutations acquired

  Study EGAS00001000874

• NIH RECOVER: A Multi-Site Pathology Study of Post-Acute Sequelae of SARS-CoV-2 Infection

  The RECOVER tissue pathology study is a cross-sectional study designed to define and characterize the epidemiology, natural history, clinical spectrum, and underlying mechanisms of post-acute effects of SARS-CoV-2 infection in a diverse population representative of the general COVID-19 population in the US. The autopsy study will characterize the pathology of PASC in decedents who die more than 60 days after initial onset or after hospital discharge, whether in-hospital or out-of-hospital at time of death, and who meet the working definition of PASC as defined by the recent World Health Organization publication given in Section 5.4. The autopsy study will also explore the pathology of acute SARS-CoV-2 infection in a smaller subset of decedents who died between15-60 days from symptom onset. This protocol defines the common set of clinical data elements, autopsy procedures for tissue collection, core measures, pathology protocols, shared pathology tissues, data elements, and methodology. Each investigator site is expected to perform autopsies on the decedents to address the pathophysiology of the potential long-term effects of SARS-CoV-2 infection on human health. The Consortium analysis plan aims to address research questions by incorporating: 1) tissue obtained from autopsies performed at each Phase II participant's site; and 2) tissue available from other pathology investigators/autopsy sites within the Consortium.

  Study phs003768

• Cancer Genetic Markers of Susceptibility (CGEMS) Breast Cancer Genome-wide Association Study (GWAS) - Primary Scan: Nurses' Health Study - Additional Cases: Nurses' Health Study 2

  The initial stage of the Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer genome-wide association study (GWAS) included genotyping 528,173 SNPs (Illumina HumanHap550) in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls from the Nurses' Health Study (NHS). Subsequently, incident invasive breast cancer cases from the Nurses' Health Study 2 (NHS2) cohort were genotyped using the Illumina HumanHap 610 quad. The NHS2 cases are younger than the cases in the first stage of the CGEMS breast cancer GWAS, which only included postmenopausal women. The NHS2 cases are a mix of pre- and postmenopausal women

  Study phs000147