15041 results for "cancer studies using rna-seq"

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• MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__clear_cell_renal_cell_carcinoma

  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. 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.

  Study EGAS00001002608

• clonealign: 10X genomics chromium single-cell RNA-sequencing

  10X genomics chromium single-cell RNA-sequencing of (i) patient derived triple negative breast cancer xenograft (ii) primary tumour and ascites ovarian cancer cell lines at tumour recurrence.

  Dataset EGAD00001004552

• Massively parallel single-cell B-cell receptor sequencing enables rapid discovery of diverse antigen-reactive antibodies

  Using high-throughput single-cell B-cell receptor sequencing (scBCR-seq) we obtained accurately paired full-length heavy- and light-chain variable regions from thousands of individual B cells in a massively parallel fashion. We sequenced more than 250,000 B cells from rat, mouse and human repertoires to characterize their lineages and expansion. In addition, we immunized rats with chicken ovalbumin and profiled antigen-reactive B cells from lymph nodes of immunized animals. The scBCR-seq data recovered 81% (n = 56/69) of B-cell lineages identified from hybridomas generated from the same set of B cells that were subjected to scBCR-seq. Importantly, scBCR-seq identified an additional 710 candidate lineages that were not recovered as hybridomas. We synthesized, expressed and tested 93 clones from the identified lineages and found that 99% (n = 92/93) of the clones were antigen-reactive. Our results establish scBCR-seq as a powerful tool for antibody discovery.

  Study EGAS00001003663

• scRNA seq Data set

  This data set contains the raw FASTq files and processed files of scRNA seq experiment which were conducted on 3 EMD samples. The libraries were generated using 10x genomics Dual index Single Cell 3' v3.1. The processed files are TSV files of features, barcodes, and gene expression matrix

  Dataset EGAD50000000334

• Single-Cell Mitochondrial Variant Profiling via TAMITO-seq

  This dataset focuses on mitochondrial variant detection using the TAMITO-seq protocol. A pre-designed mitochondrial panel (https://designer.missionbio.com/catalogpanels/Virtual-mtDNA) was spiked into the scTAMseq workflow targeting 200 CpGs and 167 genotyping loci. Data were generated from a peripheral blood sample of a healthy donor, donor X.2, multiplexed with data from another donor.

  Dataset EGAD00001015494

• Evaluation of novel therapies using primary cultured gynecological cancer cells and search for predictors of efficacy

  The objective of this study is to establish an optimal method to evaluate the anti-tumor efficacy and biological activity of the novel therapies under investigation in our department using cancer tissues and cells derived from patients with gynecological malignancies in vitro and to evaluate them in practice. This research will contribute to the development of new treatments for gynecological cancer.

  Study JGAS000809

• RNASeq Whole Transcriptome Expression Profiles of NFE2 and PF4 as Translational Biomarkers for BET Inhibition-Induced Thrombocytopenia in Preclinical and Clinical Studies

  Longitudinal blood samples for exploratory biomarker analysis were collected from 51 out of 83 patients enrolled in CA011-001 (NCT02419417) study of BMS-986152, totaling 425 samples collected on three different dosing schedules (A, B, and C). Whole transcriptome expression profiling was performed on the collected blood samples using RNASeq, with Illumina TruSeq library preparation and paired sequencing. Gene expression data was quantified as transcripts per million (TPM).

  Dataset EGAD50000001659

• H3K27ac ChIP-seq in primary inflammatory macrophages from 2 minor allele homozygotes and 2 major allele homozygotes at rs2836882

  This dataset consists of H3K27ac ChIP-sequencing in inflammatory (TPP) macrophages from 2 minor allele homozygotes and 2 major allele homozygotes at rs2836882. Monocytes were positively selected from PBMC using CD14 Microbeads and inflammatory macrophage differentiation performed using conditions that model chronic inflammation (TPP): 3 days GM-CSF (50ng/mL) followed by 3 days GM-CSF, TNFa (50ng/mL), PGE2 (1mg/mL), and Pam3CSK4 (1mg/mL). After harvesting, cells were cross-linked, quenched, lysed, and sheared. Immunoprecipitation of histone-DNA complexes was performed overnight at 4C with rotation using an anti-H3K27ac antibody and the SimpleChIP Plus Sonication ChIP kit (Cell Signaling Technology). Following reverse cross-linking, 50ng of immunoprecipitated DNA or input DNA were used to prepare sequencing libraries using the iDeal Library Preparation kit (Diagenode), according to manufacturer instructions. 10 PCR cycles were used for the amplification step and size selection was not performed. The quality and molarity of all libraries was assessed using a BioAnalyzer 2100 (Agilent) and the libraries were sequenced in pools of 8, with each pool being sequenced in 2 lanes of an Illumina HiSeq2500 high output flow-cell (50bp, single-end reads). Raw data are provided as raw and aligned single-end sequencing reads from H3K27ac-bound DNA and the input chromatin. Raw reads were trimmed using Trim Galore and aligned to the reference human genome (hg19) using Burrows-Wheeler Aligner (v0.7.12) with default parameters. Aligned reads were converted to BAM files, sorted, and technical duplicates merged before indexing – all using SAMtools (v1.4). PCR duplicates were identified using Picard tools (v2.18.1) and removed together with unmapped reads using SAMtools (v1.4). The resulting BAM files were re-sorted and indexed after filtering.

  Dataset EGAD00001011351

• CD4 T Cell Subsets in Human Metastatic Melanoma

  We used single-cell RNA-sequencing (scRNA-seq) to define CD4+ T-cell subsets in melanoma tumors from patients undergoing tumor resection. All patients received immune checkpoint blockade prior to surgery. We identified multiple subsets in the tumor with transcriptional features of suppressive function, including TR1 cells and FOXP3+ Treg cells. Based on transcriptional profiles, classical helper T cell subsets were not prevalent.

  Study phs003816

• Integrative understanding of human immune system by functional genomics and development of intervention strategies for the prevention of autoimmune diseases

  arious peripheral blood immune cell subsets from 5 rheumatoid (RA) donors were collected ("CD16p_Mono", "CL_Mono???, "DN_B", "Fr_II_eTreg???, "mDC???, "Mem_CD4" , "Naive_B" , "Naive_CD4" , ???Neu", "NK" , "pDC" , "Plasmablast", ???SM_B", "Tfh", "Th1", "Th17", "Th2" , "USM_B"). The patients were analyzed again longitudinally after abatacept treatment. RNA-seq was performed with each immune cell subset samples. After gene expression quantification samples were filtered.

  Study JGAS000602

• Integrative understanding of human immune system by functional genomics and development of intervention strategies for the prevention of autoimmune diseases

  Various peripheral blood immune cell subsets from 39 healthy volunteers and 50 rheumatoid (RA) donors were collected ("CD16p_Mono", "CL_Mono???, "DN_B", "Fr_II_eTreg???, "mDC???, "Mem_CD4" , "Naive_B" , "Naive_CD4" , ???Neu", "NK" , "pDC" , "Plasmablast", ???SM_B", "Tfh", "Th1", "Th17", "Th2" , "USM_B"). 15 RA patients were analyzed longitudinally. RNA-seq was performed with each immune cell subset samples. After gene expression quantification samples were filtered.

  Study JGAS000598

• The genomic landscape of Burkitt Lymphoma

  As part of the ICGC, the ICGC MMML-Seq project performed whole genome sequencing and RNA sequencing of Burkitt Lymphomas . Burkitt lymphomas are the most common B-cell lymphomas in childhood. Analyses were performed in concordance with the guidelines of the ICGC. The results define the genomic landscape of structural variants, somatic single nucleotide variants and mutational signatures in these lymphomas.

  Study EGAS00001002198

• Molecular landscape of blastic plasmacytoid dendritic cell neoplasm

  Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive malignancy assumed to originate from plasmacytoid dendritic cells (pDCs), which mostly affects the skin, bone marrow and lymph nodes and sequentially other organ systems. We applied paired WES/RNA-seq combined with genome-wide copy-number analysis to characterize 47 BPDCN patients regarding mutational drivers, cytogenetic aberrations and gene-expression profiles.

  Study EGAS00001006166

• Extensive patient-to-patient single nuclei transcriptome heterogeneity in pheochromocytomas and paragangliomas

  Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors of varied genetic makeup, associated with high cardiovascular morbidity and a variable risk of malignancy. We focused on PCPG tumors with germline SDHB and RET mutations, representing distinct prognostic groups with worse or better prognoses, respectively. We applied single-nuclei RNA sequencing (snRNA-seq) on tissue samples from 11 patients.

  Study EGAS00001006230

• Genetic regulation of gene expression in human brain cell types

  We leveraged single nuclei RNA-seq from 192 human brain samples to map cis-eQTLs in 8 brain cell types. We found extensive cell-type specific genetic effect on gene expression and integrated our results with GWAS to identify putative novel risk genes for brain disorders and the cell types in which the disease mechanisms are likely active.

  Study EGAS00001006345

• 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

• Characterization of Immune-Related Gene Expression in Lung Cancer

  We performed a comprehensive analysis of inter- and intratumor heterogeneity of immune gene expression in 160 lung cancer patients from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. The transcriptome was profiled with RNA sequencing in 269 tumor samples and 110 normal tissue samples from 160 subjects.

  Study phs002346

• Studying the single cell characteristics of pancreatic cancer

  Pancreatic cancer is a dangerous malignancy in the pancreas. In this study we use single-cell RNA sequencing technique to help understand the transcriptome characteristics of pancreatic tumor cells. This study help understands the complex microenvironment of pancreatic tumors and will likely to benefit clinical research of pancreatic cancer treatments.

  Study EGAS00001003889

• Immune Responses in Checkpoint Myocarditis Across Heart, Blood, and Tumor

  Immune checkpoint inhibitors (ICIs) are widely used in anti-cancer therapies, but they can cause morbid and potentially fatal immune-related adverse events (irAEs), such as ICI-related myocarditis (irMyocarditis). The pathogenesis of irMyocarditis and its relationship to anti-tumor immunity remain poorly understood. We sought to define immune responses in heart, tumor, and blood in irMyocarditis patients and controls by leveraging single‐cell RNA sequencing (scRNA‐seq) coupled with T-cell Receptor Sequencing (TCR-Seq). Our analysis demonstrated increased frequencies of cytotoxic T cells, inflammatory mononuclear phagocytes (MNPs), conventional dendritic cells (cDCs), and inflammatory fibroblasts in irMyocarditis heart tissue. Additionally, we revealed decreased frequencies of plasmacytoid dendritic cells, cDCs, and B lineage cells but an increased frequency of MNPs in the blood of irMyocarditis patients. Raw data for heart and blood can be found in dbGaP. All processed data and raw TCRseq data from heart tissue and tumor samples for this study can be found in GEO (Accession number GSE228597).Subject IDs with the prefix "SIC" were collected by the Severe Immunotherapy Complications (SIC) service at MGH due to suspicion of immune-related adverse events. Subject IDs with the prefix "donor" were collected by the MGH Melanoma Biobank at scheduled timepoints; this biobank systematically collects samples from patients at MGH at clinically relevant timepoints.

  Study phs003413

• Mapping the epigenomic landscape of human monocytes following innate immune activation reveals context-specific mechanisms driving endotoxin tolerance

  Background Monocytes are key mediators of innate immunity to infection, undergoing profound and dynamic changes in epigenetic state and immune function which are broadly protective but may be dysregulated in disease. Here, we aimed to advance understanding of epigenetic regulation following innate immune activation, acutely and in endotoxin tolerant states. Methods We exposed human primary monocytes from healthy donors (n=6) to interferon-γ or differing combinations of endotoxin (lipopolysaccharide), including acute response (2hr) and two models of endotoxin tolerance: repeated stimulations (6+6hr) and prolonged exposure to endotoxin (24hr). Another subset of monocytes was left untreated (naïve). We identified context-specific regulatory elements based on epigenetic signatures for chromatin accessibility (ATAC-seq) and regulatory non-coding RNAs from total RNA sequencing. Results We present an atlas of differential gene expression for endotoxin and interferon response, identifying widespread context specific changes. Across assayed states, only 24-29% of genes showing differential exon usage are also differential at the gene level. Overall, 19.9% (6884 of 34616) of repeatedly observed ATAC peaks were differential in at least one condition, the majority upregulated on stimulation and located in distal regions (64.1% vs 45.9% of non-differential peaks) within which sequences were less conserved than non-differential peaks. We identified enhancer-derived RNA signatures specific to different monocyte states that correlated with chromatin accessibility changes. The endotoxin tolerance models showed distinct chromatin accessibility and transcriptomic signatures, with integrated analysis identifying genes and pathways involved in the inflammatory response, detoxification, metabolism and wound healing. We leveraged eQTL mapping for the same monocyte activation states to link potential enhancers with specific genes, identifying 1,946 unique differential ATAC peaks with 1,340 expression associated genes. We further use this to inform understanding of reported GWAS, for example involving FCHO1 and coronary artery disease. Conclusion This study reports context-specific regulatory elements based on transcriptomic profiling and epigenetic signatures for enhancer-derived RNAs and chromatin accessibility in immune tolerant monocyte states, and demonstrates the informativeness of linking such elements and eQTL to inform future mechanistic studies aimed at defining therapeutic targets of immunosuppression and diseases.

  Study EGAS00001007362

• Genome-Wide Analysis for Addiction Susceptibility Genes

  Genome wide analysis for addiction susceptibility genes is an affected sibling pair linkage study using subjects who were patients in methadone replacement treatment programs (MMTP). Such patients are highly addicted to opioids and usually to other addicting substances as well. For entry into the programs, patients had to be at least 18 years of age and had to satisfy DSM-IV criteria for opioid dependence. Despite their common substance use disorder diagnosis, patients enrolled in MMTPs generally have a heterogeneous mix of co-morbid psychiatric disorders including anti-social personality disorder, major depression and anxiety disorders, and often satisfy DSM-IV criteria of substance use disorders other than opioid dependence. Genetic analysis was carried out using genotyping data obtained from a 10K SNP array, and non-parametric linkage was assessed using MERLIN. This resulted in the identification of a linkage peak on 14q that overlapped the NRXN3 gene (neurexin 3), which was previously identified as a potential candidate gene for addiction, and subsequently identified as a target gene in other addiction studies and autism. In version 2 of this study, a text file containing 7704 SNPs with large allele frequency discrepancy as compared to 1000 Genomes is included. Users have the option to exlude these 7704 SNPs.

  Study phs001266

• Enhanced Adjuvanticity of a Personal Neoantigen Vaccine Generates Potent Neoantigen-Specific Immunity

  Personalized neoantigen-targeting vaccines can induce durable and diverse T cell responses and have been associated with improved outcomes. To augment immunogenicity, we tested a synthetic long peptide vaccine formulated with the adjuvants Montanide and poly-ICLC in 10 patients with melanoma. The vaccines, co-administered locally with ipilimumab and systemically with nivolumab, generated de novo ex vivo T cell responses against the majority of immunizing neoepitopes in all 9 fully vaccinated patients, and ex vivo CD8+ T cell responses in 6 of 9. Hundreds of circulating and intratumoral T cell receptor (TCR) clonotypes emerged following vaccination that were distinct from those arising after PD-1 inhibition. By linking vaccine-specificity and cellular phenotype of TCRs in post-treatment tumors at single cell resolution, we demonstrate remodeling of the intratumoral T cell repertoire following vaccination. These observations demonstrate the impact of multi-pronged immune adjuvanticity on the T cell repertoire in the context of neoantigen-targeting vaccines. We are submitting WES data from whole blood samples and tumor FFPE samples, and RNA-seq data from tumor FFPE samples. We are also submitting RNA-seq data from purified tumor samples. scRNA-seq data will also be submitted for skin samples (pre and post neoantigen vaccine dose #3), and tumor samples before starting treatment, before starting neoantigen vaccine Dose #1, and before neoantigen vaccine dose #4. Bulk TCR-seq data will be submitted for blood samples.

  Study phs003919

• snRNA and snATAC analysis of cocaine use disorder in human caudate nucleus

  We investigated cell type specific changes of gene expression and chromatin accessibility in the caudate nucleus of N=6 individuals with and N=8 individuals without cocaine use disorder using postmortem human brain samples. We performed single-nuclei RNA-sequencing and single-nuclei ATAC sequencing in the same cells using the 10xMultiome platform. The N=14 tissue donors were of African-American ancestry. The cohort consists of N=5 female and N=9 male individuals.

  Study EGAS50000000480

• TPM for IMpower133 (GO30081)

  This dataset contains log2(TPM + 1) for 271 tumor samples profiled by RNA-seq for the entire transcriptome for samples originating from IMpower133 (GO30081).

  Dataset EGAD50000000196

• RNA-seq data of CRC-PDX tumors after drug treatment

  We obtained bulk RNAseq data of CRC-PDX tumors after administration of drug or vehicle to clarify the mechanisms of action.

  Dataset EGAD50000000849

• Convergent genetic adaptation in human tumors developed under systemic hypoxia and in populations living at high altitudes

  Genomic files, including whole-exome and RNA-seq data from tumors and cell lines, were generated and analyzed in this study.

  Dac EGAC50000000484

• RNA-seq of murine osteosarcoma cell line genetically modified for CYR61

  Transcriptomic analysis of K7M2 murine osteosarcoma cells stably modified to overexpress or repress CYR61

  Study EGAS50000000526

• Melanoma transcriptome profiling

  This dataset includes transcriptome profiling of 68 early-passage metastatic melanoma cell lines. The data are provided as paired-end RNA seq fastq files.

  Dataset EGAD00001006270

• Melanoma microRNA profiling

  This dataset includes microRNA profiling of 61 early-passage metastatic melanoma cell lines. The data are provided as single-end small RNA seq fastq files.

  Dataset EGAD00001006269

• HDAC inhibitor quisinostat in synovial sarcoma cell lines

  An RNA Seq study of the effects of HDAC inhibitor Quisinostat on six different synovial sarcoma cell lines

  Dataset EGAD00001003810

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

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

  Study EGAS00001003172

• Molecular determinants of response to PD-L1 blockade across tumor types

  Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis lead to durable clinical responses in subsets of cancer patients across multiple indications, including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC) and renal cell carcinoma (RCC). Herein, we complement PD-L1 immunohistochemistry (IHC) and tumor mutation burden (TMB) with RNA-seq in 366 patients to identify unifying and indication-specific molecular profiles that can predict response to checkpoint blockade across these tumor types. Multiple machine learning approaches failed to identify a baseline transcriptional signature highly predictive of response across these indications. Signatures described previously for immune checkpoint inhibitors also failed to validate. At the pathway level, significant heterogeneity was observed between indications, in particular within the PD-L1+ tumors. mUC and NSCLC were molecularly aligned, with cell cycle and DNA damage repair genes associated with response in PD-L1- tumors. At the gene level, the CDK4/6 inhibitor CDKN2A was identified as a significant transcriptional correlate of response, highlighting the association of non-immune pathways to the outcome of checkpoint blockade. This cross-indication analysis revealed molecular heterogeneity between mUC, NSCLC and RCC tumors, suggesting that indication-specific molecular approaches should be prioritized to formulate treatment strategies.

  Study EGAS00001004343

• NHLBI TOPMed: HyperGEN - Genetics of Left Ventricular (LV) Hypertrophy

  The Hypertension Genetic Epidemiology Network Study (HyperGEN) - Genetics of Left Ventricular (LV) Hypertrophy is a familial study aimed to understand genetic risk factors for LV hypertrophy by conducting genetic studies of continuous traits from echocardiography exams. The originating HyperGEN study aimed to understand genetic risk factors for hypertension. Data from detailed clinical exams as well as genotyping data for linkage studies, candidate gene studies and GWAS have been collected and is shared between HyperGEN and the ancillary HyperGEN - Genetics of LV Hypertrophy study.

  Study phs001293

• ChIP-Seq (H3K4me3, H3K4me1, H3K9me3, H3K27ac, H3K27me3, H3K36me3, Input) data for HL60 cell line generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency.

  ChIP-Seq (H3K4me3, H3K4me1, H3K9me3, H3K27ac, H3K27me3, H3K36me3, Input) data for HL60 cell line generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency.

  Dataset EGAD00001002238

• Oncoarray Consortium - Lung Cancer Studies

  The study was conducted under the auspices of the Transdisciplinary Research In Cancer of the Lung (TRICL) Research Team, which is a part of the Genetic Associations and MEchanisms in ONcology (GAME-ON) consortium, and associated with the International Lung Cancer Consortium (ILCCO). Ethics: All participants provided written informed consent. All studies were reviewed and approved by institutional ethics review committees at the involved institutions. Sequencing data are derived from four substudies. The substudies that contributed include Harvard, Liverpool, Toronto, and IARC. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study is a randomized primary prevention trial including 29,133 male smokers enrolled in Finland between 1985 and 1993. Participants ranged between ages of 50 to 69 at enrollment and were randomized in a factorial design to take either 50 milligrams of d-alpha tocopheryl acetate (Vitamin E), 20 mg of all-trans-beta-carotene, both or placebo. The study continued to monitor cancer incidence through 2012 and total mortality through December 2013. The CAncer de PUlmon en Asturias Study (CAPUA) is a hospital-based case-control study conducted in Asturias, Spain by the University of Oviedo. Lung cancer cases were recruited in three main hospitals of Asturias, following an identical protocol from 2002 to 2012. Eligible cases were incident cases of histologically confirmed lung cancer between 30 and 85 years of age and residents in the geographical area of each participating hospital. Controls were selected from patients admitted to those hospitals with diagnoses unrelated to the exposures of interest and individually matched by ethnicity, gender, age (± 5 years) and hospital. Epidemiologic data were collected personally through computer-assisted questionnaires by trained interviewers during the first hospital admission. Structured questionnaires collected information on sociodemographic characteristics, recent and prior tobacco use, environmental exposure (air pollution and passive smoking), diet, personal and family history of cancer, and occupational history from each participant. Peripheral blood samples (or mouthwash samples when they refused to donate blood) were collected from all participants. Coding of histology was based on 2001 WHO/IASLC. Genomic DNA was extracted based on standard protocol. The Canadian Screening Study includes the nested case-control samples from 3 screening programs: IELCAP-Toronto: Ever smokers of more than 10 pack-years age 50 and above were eligible for the I-ELCAP screening program since 2003, and a total of 4782 individuals have been enrolled in the Greater Toronto Area. Participants were administered a LDCT scan along with a standard study questionnaire at baseline. Blood samples were systematically collected at baseline since 2006. Participants who had an abnormality in a CT scan were followed up every 1 to 2 years. The screening program was organized by the Princess Margaret Hospital. PanCan: Ever smokers between the ages of 50-75 with no previous history of invasive cancer are eligible to participate in the study. The study was carried out across Canada in Vancouver, Calgary, Hamilton, Toronto, Ottawa, Quebec, Halifax, and St. John's. A total of 2537 smokers have been screened from 2008 to 2011. All study participants completed a detailed questionnaire, spirometry, collection of blood specimens for biomarker measurement and LDCT at baseline. All participants are followed for a minimum of 3 years. On yearly follow up, an updated shorter questionnaire is administered, blood is collected and CT scans are performed. Blood samples are available from all 2537 individuals. BCCA Screening Program: From 1990 to 2007, 4274 smokers above 40 years old who had smoked 20 pack-years or more were enrolled at BCCA. Upon enrollment, subjects completed a questionnaire for their lifestyle and medical history. Baseline spirometry was conducted using a flow-sensitive spirometer in accordance with the American Thoracic Society recommendations. Since 2000, a LDCT was obtained in 2440 individuals. The participants were followed prospectively to determine whether they developed lung cancer. A total of 9759 individuals participated in the CT screening program in Canada from these 3 programs. The samples included in this project is based on a subset of nested lung cancer case-control pairs based on 1:2 ratio. The Carotene and Retinol Efficacy Trial (CARET) was a randomized, double-blind, placebo-controlled trial of the cancer prevention efficacy and safety of a daily combination of 30 mg of beta-carotene and 25,000 IU of retinyl palmitate in 18,314 persons at high risk for lung cancer. CARET began in 1985, and the intervention was halted in January 1996, 21 months ahead of schedule, with the twin conclusions for definitive evidence of no benefit and substantial evidence of a harmful effect of the intervention on both lung cancer incidence and total mortality. CARET continued to follow and collect endpoints on their participants through 2005. Pathology reports and medical records were reviewed to confirm cancer endpoints, and death certificates obtained to capture cause of death. During the active intervention phase of CARET, serum, plasma, whole blood, and lung tissue specimens were collected on participants. These biospecimens make up the CARET Biorepository. For the OncoArray Project, CARET provided DNA extracted from whole blood of lung cancer cases and controls matched on age at baseline (± 4 years), sex, race, baseline smoking status, history of occupational asbestos exposure (asbestos vs heavy smoker), and year of enrollment (2-year intervals). The European Prospective Investigation into Cancer and Nutrition (EPIC) study is a multi-center cohort study involving 521,000 study participants from 10 European countries. The current study involved EPIC participants from 7 countries (Greece, Netherlands, UK, France, Germany, Spain, and Italy), including 1223 incident lung cancer cases and 1249 smoking matched controls. The Kentucky Lung Cancer Research Initiative is a study conducted by the Markey Cancer Center Cancer Center and the University of Kentucky using a population-based, case-control framework to study the extraordinarily high rates of lung cancer in Southeastern, Appalachian Kentucky. Cancer cases were recruited from the Kentucky Cancer Registry at the time of diagnosis and controls were recruited from a random digit dialing process from the same region. Study accrual began in January 5, 2012 and completed on September 5, 2014 and 520 subjects were recruited in a 4:1 ratio of controls: cases from Appalachian Kentucky. Of the 520 subjects recruited, 231 are included in the OncoArray analysis, including all 93 cancer cases, and 123 controls. Newly diagnosed lung cancer cases and controls underwent blood, toenail (for trace element analysis), urine, buffy coat, water, soil, and radon collection, residence GPS mapping, as well as an extensive epidemiologic, occupational, and health history questionnaire (Clinical Trials.gov Identifier: NCT01648166). The Harvard Lung Cancer Study (HLCS) is a case-control study based at Mass General Hospital (MGH) in Boston, Massachusetts from 1992 to 2004. Details of the study were described previously. Briefly, eligible cases included any person over the age of 18 years with a diagnosis of primary lung cancer that was further confirmed by an MGH lung pathologist. Controls were recruited from the friends or spouses of cancer patients or the friends or spouses of other surgery patients in the same hospital. Potential controls were excluded from participation if they had a diagnosis of any cancer (other than non-melanoma skin cancer). Interviewer-administered questionnaires, a modified version of the standardized American Thoracic Society respiratory questionnaire, collected information on demographics, medical history, family history of cancer, smoking history, and a detailed work history, including job titles and tasks. Genome-wide genotype data were first generated using Illumina Human 610-Quad BeadChips and then imputed by MACH against the 1000 Genome Project dataset (http://browser.1000genomes.org/index.html). The Institutional Review Board of MGH and the Human Subjects Committee of the Harvard School of Public Health approved the study. The Israel study (NICCC-LCA) is an ongoing case-control study of newly diagnosed lung cancer cases of any histology and population age/sex/ethnicity-matched "healthy" controls. All participants undergo face-to-face interviews, provide a venous blood sample (separated into DNA, Sera, lymphocytes) after signing an IRB-approved form. Histology reports, FFPE blocks and clinical follow-up are available for most cancer cases. The MD Anderson Cancer Center (MDACC) Study. Lung cancer cases and frequency-matched controls were ascertained from a large ongoing case-control study at the University of Texas MD Anderson Cancer Center (UTMDACC) since 1991. Detailed study description was provided previously (Spitz et al 2007). In brief, cases were newly-diagnosed and histologically confirmed lung cancer patients recruited from UTMDACC. Controls were healthy individuals without a history of cancer (except for nonmelanoma skin cancer) and recruited from the Kelsey-Seybold Clinics, the largest private multispecialty physician group in the Houston metropolitan area. Controls were frequency-matched to cases on age (±5 years), sex, and race/ethnicity. After providing written informed consent, each study participants completed an in-person interview by staff interviewers to collect information on demographics, smoking status, etc. Blood samples were also drawn from all the study participants. This study was approved by institutional review boards of UTMDACC and Kelsey-Seybold Clinics. The Malmö Diet and Cancer Study (MDCS) is a population-based prospective cohort study that recruited men and women aged at 44 to 74 years old of living in Malmö, Sweden between 1991 and 1996. The main goal of the MDCS is to study the impact of diet on cancer incidence and mortality. It consists of a baseline examination including dietary assessment, a self-administered questionnaire, anthropometric measurements and collection of blood samples. A total of 165 incident lung cancer cases and 174 individually smoking-matched controls were available for this analysis. The Multiethnic Cohort (MEC) Study includes 215,251 men and women aged 45-74 years at recruitment, primarily from five ethnic/racial groups - African Americans and Latinos mostly recruited from CA (mainly from Los Angeles County) and Japanese Americans, Native Hawaiians and whites (mostly recruited from HI). The cohort was assembled in 1993-1996 by mailing a self-administered questionnaire to persons identified primarily through driver's license files. The baseline questionnaire obtained information on demographics, anthropometry, smoking history, medical and reproductive histories, family history of cancer, diet and physical activity. Incident cancer cases are identified by regular linkage with the State of California Cancer Registry and the Hawaii Tumor Registry, both members of the SEER Program of the NCI. In 2001-2006, a prospective biorepository was assembled by collecting a pre-diagnostic blood specimen from 67,594 surviving MEC members. At the time of blood collection a short questionnaire was administered that included information on smoking during the previous 15 days. For this study, cases were all lung cancer cases incident to blood draw and diagnosed before December 2012. For each case, a control was selected among unaffected MEC participants who were alive at time of the case's diagnosis and matched on study site, sex, race/ethnicity, age (age at diagnosis for cases; age at blood collection for controls), and date of blood collection. The Mount-Sinai Hospital-Princess Margaret Study (MSH-PMH) was conducted in the greater Toronto area from 2008 to 2013. Lung cancer cases were recruited at the hospitals in the network of the University of Toronto. Controls were selected randomly from individuals registered in the family medicine clinics databases and were frequency matched with cases on age and sex. All subjects were interviewed, and information on lifestyle risk factors, occupational history and medical and family history was collected using a standard questionnaire. Tumors were centrally reviewed by the reference pathologist, a member of the International Association for the Study of Lung Cancer (IASLC) committee, and a second pathologist in the University Health Network. If the reviews conflicted, a consensus was arrived at after discussion. Coding of histology was based on 2001 WHO/IASLC. Genomic DNA was extracted based on standard protocol. The New England Lung Cancer Study (NELCS) is a population-based case-control study of lung cancer among residents of Northern and Central New Hampshire counties and the bordering region of Vermont. Cases with histologically confirmed primary incident lung cancer were identified from 2005 to 2007 using the New Hampshire State Cancer Registry and the Dartmouth-Hitchcock Medical Center (DHMC) Tumor Registry. Control participants were identified using a commercial database and matched to lung cancer cases within 5-year age groups, sex and county. Genomic DNA was isolated from blood or buccal specimens provided by consenting participants. The study complied with requirements of the Dartmouth College's Committee for Protection of Human Subjects. The Nijmegen Lung Cancer Study. The Netherlands patients with lung cancer were identified through the population-based cancer registry of the Netherlands Comprehensive Cancer Organisation in Nijmegen, the Netherlands. Patients who were diagnosed in one of three hospitals (Radboud University Medical Center, Canisius Wilhelmina Hospital in Nijmegen, and Rijnstate Hospital in Arnhem) since 1989 and who were still alive at April 15th, 2008 were recruited for a study on gene-environment interactions in lung cancer. 458 patients gave informed consent and donated a blood sample. This case series was expanded with 94 patients to a total of 552 by linking three other studies to the population-based cancer registry in order to identify new occurrences of lung cancer among the participants of these other studies. All three other studies (i.e., POLYGENE, the Nijmegen Biomedical Study, and the Radboudumc Urology Outpatient Clinic Epidemiology Study) were initiated to study genetic risk factors for disease and participants to these studies gave general informed consent for DNA-related research and linkage with disease registries. Information on histology, stage of disease, and age at diagnoses was obtained through the cancer registry. Lifestyle information was collected through a structured questionnaire and whole blood for DNA isolation was collected by the regional thrombosis services. The cancer-free controls (46% males) were selected from participants of the "Nijmegen Biomedical Study" (NBS), an age- and sex-stratified random sample of the general population of the municipality of Nijmegen, The Netherlands. All participants provided extensive lifestyle information by structured questionnaires and blood samples for DNA isolation, serum and plasma. All controls are of self-reported European descent. The study protocols of the NBS were approved by the Institutional Review Board of the Radboudumc and all study subjects signed a written informed consent form. The Northern Sweden Health and Disease Study (NSHDS) encompasses several prospective cohorts. The current study involves participants from the Västerbotten Intervention Project (VIP), a sub-cohort within NSHDS. VIP is an ongoing prospective cohort and intervention study intended for health promotion of the general population of the Västerbotten County in northern Sweden. VIP was initiated in 1985 and all residents in the Västerbotten County were invited to participate by attending a health check-up at 40, 50 and 60 years of age. Participants were asked to complete a self-administered questionnaire including various demographic factors such as education, smoking habits, physical activity and diet. In addition, height and weight were measured and participants were asked to donate a fasting blood sample for future research. A total of 243 incident lung cancer cases and 266 individually smoking-matched controls were available for this analysis. Norway National Institute of Occupational Health Study. Early-stage NSCLC cases and healthy controls at the time of enrollment were Caucasians of Norwegian origin and were recruited from the same geographical region (Western Norway). The patients were enrolled in the study, whenever practically feasible among patients admitted for lung cancer at the Haukeland University Hospital in Bergen, Norway. The informed written consents covering analysis of molecular and genetic markers was signed by the patients prior to surgery. Only patients with histologically confirmed early-stage NSCLC were included in our study. The subjects included in this project are a subgroup recruited into the project "lung cancer genetics" at NIOH. The controls were recruited from the same geographical region of Western Norway and frequency-matched with cases on cumulative smoking dose (pack-years). Pack-years smoked [( 20 cigarettes per day) x years smoked] were calculated to indicate the cumulative smoking dose. The Cases and controls were interviewed using similar questionnaires and were categorized as never smokers, ex-smokers or current smokers. Never smokers are subjects indicating having smoked less than 100 cigarettes in their life time. Ex-smokers were defined as those having quitted at least 1 year before sampling, and current smokers were those indicating that they were smokers at the time of sampling. The project has been approved by the Regional Committee for Medical and Health Research Ethics in Southern Norway in accordance with the WMA Declaration of Helsinki. The ethical approval covered access to the NSCLC databank. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Study, a randomized trial aimed at evaluating the efficacy of screening in reducing cancer mortality, recruited approximately 155,000 men and women age 55 to 74 years from 1992 to 20014. Screening for lung cancer among participants in the intervention arm included a chest x-ray at baseline followed by either three annual x-rays (for current or former smokers at enrollment) or two annual x-rays (for never smokers); participants in the control arm received routine health care. Screening-arm participants provided data on sociodemographic factors, smoking behavior, anthropometric characteristics, medical history, and family history of cancer, as well as blood samples annually for the first 6 years of the study (baseline T0 and T1 through T5). Lung cancers were ascertained through annual questionnaires mailed to the participants, and positive reports were followed up by abstracting medical records or death certificates. Follow-up in the trial as of July 2009 was 96.7%. Patients were excluded because of missing baseline questionnaire, previous history of any cancer, diagnosis of multiple cancers during follow-up, missing smoking information at baseline, missing consent for utilization of biologic specimens for etiologic studies, or unavailability/insufficient quantity of serum or DNA specimens. The Resource for the Study of Lung Cancer Epidemiology in North Trent (ReSoLuCENT) is an ongoing study conducted in Sheffield from 2006 and due to complete recruitment in 2016. The study recruited pathologically confirmed lung cancer cases diagnosed at age 60 years or younger and family matched controls. Lung cancer cases diagnosed at ages older than 60 years were recruited if they reported a family history of lung cancer. The cases and matched controls were recruited through several major cancer treatment centers, however, the majority were recruited in North Trent. All participants completed a detailed lifestyle questionnaire which included questions about occupational exposures, education, medical history and family history of cancer and lung disease. Participants also donated blood samples for DNA extraction. The ReSoLuCENT study has been funded by the Sheffield Hospitals Charity, Sheffield ECMC and Weston Park Hospital Cancer Charity. First degree relatives were removed from the sample deposited to dbGaP. The Roy Castle Lung Study of Liverpool Lung Project (LLP) is a case-control and cohort study which has recruited over 11,500 individuals since 1996 from the Liverpool region in the UK. Detailed epidemiological and clinical data is collected with associated specimens (i.e. tumor tissue, blood, plasma, sputum, bronchial lavage and oral brushings). The participants have completed a detailed lifestyle questionnaire at recruitment, with repeat questionnaires at intervals; updated data on clinical outcome and hospital events are collected through the Health and Social Care Information Center (including Office of National Statistics mortality data, Cancer Registry and Health Episode Statistics). The project is registered on the UK National Institute for Health Research (NIHR) lung cancer portfolio and has all the required ethical approvals and sponsorship arrangements in place. The lung tumors were reviewed by the reference pathologist. The Seoul Bundang Lung Cancer Study was conducted between 2005 and 2010 to discover genetic and environmental factors related with lung cancer development. Lung cancer cases were recruited at the Seoul National University Hospital in Bundang. Controls were selected randomly from individuals participated in health check-up program and were frequency matched with cases on age and sex. All subjects were interviewed, and information on lifestyle risk factors, occupational history and medical and family history was collected using a standard questionnaire. Tumors were reviewed by the pathologists in the hospital. If the reviews conflicted, a consensus was arrived at after discussion. Coding of histology was based on 2001 WHO/IASLC. Genomic DNA was extracted based on standard protocol. The Shanghai Cohort Study (SCS) consisted of 18,244 men in Shanghai, China, who were 45-64 years old at the time of enrollment during 1986-1989. Approximately 80% of eligible men participated in the study. At the time of recruitment, each cohort subject was interviewed in-person by a trained nurse interviewer using a structured questionnaire that included background information, history of tobacco and alcohol use, current diet, and medical history. At the completion of the interview, the nurse collected a 10 ml blood and a single void urine specimen from the study participant. The buccal cell samples were collected from all surviving cohort members (~15,000) in the 2001-2002 follow-up interviews. The cohort has been followed for the occurrence of cancer and death through routine ascertainment of new cases from the population-based Shanghai Cancer Registry and Shanghai Vital Statistics Units. To maximize the cancer findings and minimize the loss of follow-up, we contacted each surviving cohort member annually. Retired nurses visit the last known address of each living cohort member and record details of the interim health history of the cohort member. As of December 31, 2014, cumulatively 612 (3.4%) original subjects were lost to follow-up, and 574 (3.1%) refused to our continued follow-up interview. A nested case-control study of incident lung cancer cases within the Shanghai Cohort Study was used to examine the association between serum levels of vitamin B6 and other compounds in the one-carbon metabolism pathway and risk of lung cancer. Briefly, 516 lung cancer cases were identified among cohort participants with available serum samples as of 12/31/2006. For each case, we randomly selected one control subject from all cohort members who were free of cancer and alive at the time of cancer diagnosis of the index case. Controls were matched to the index case by age at enrollment (±2 years), date of biospecimen collection (±1 month) and neighborhood of residence at recruitment, and smoking status (current, former and never smokers) as established previously for other studies. For former smokers, cases and controls were further matched by years since quitting smoking (<10 vs ≥10 years). One serum vial per subject was retrieved from biorepository and all serum samples were sent to the laboratory (B-vital) for measurements. DNA samples of 250 lung cancer cases and 250 matched controls were available for the present study. The Singapore Chinese Health Study (SCHS) cohort consisted of 63,257 Chinese men and women in Singapore when they were 45-74 years old at the time of enrollment between April 1993 and December 1998. At recruitment, each study subject was interviewed in person by a trained interviewer using a structured questionnaire that emphasized current diet assessed via a validated, 165-item food frequency questionnaire. The questionnaire also requested information on demographics, lifetime use of tobacco, incense use, current physical activity, usual sleep duration, reproductive history (women only), occupational exposure, medical history, and family history of cancer. Blood or buccal cell, and spot urine samples were collected first from a random 3% sample of cohort participants in April 1994, and extended to all surviving cohort participants starting in January 2000. Overall approximately 60% of eligible cohort participants donated biospecimens. The cohort has been passively followed for death and cancer occurrence through regular record linkage with the population-based Singapore Cancer Registry and the Singapore Registry of Births and Deaths. Migration out of Singapore, especially among housing estate residents, was negligible. As of latest update, only 55 individuals from this cohort were known to be lost to follow-up due to migration and other reason. A nested case-control study of incident lung cancer cases within the Singapore Chinese Health Study was used to examine the association between serum levels of vitamin B6 and other compounds in the one-carbon metabolism pathway and risk of lung cancer. As of 12/31/2011, 422 lung cancer cases were identified among cohort participants with available prediagnostic plasma samples. For each case, one control subject was randomly selected from all eligible cohort members who were alive and free of cancer on the date of cancer diagnosis of the index case. The control subject was individually matched to the index case by gender, dialect group (Hokkien, Cantonese), age at enrollment (±3 years), date of baseline interview (±2 year), date of biospecimen collection (±6 months), and smoking status (current, former, and never smokers). For current smokers, cases and controls were further matched by number of cigarettes per day (<15, ≥15 cigarettes/day). For former smokers, cases and controls were further matched by years since quitting smoking (<10, ≥10 years). One plasma aliquot per subject was retrieved from the biorepository and all plasma samples were sent to the laboratory (B-vital) for measurements, and one aliquot of DNA per subject for the present study. The International Agency for Research on Cancer (IARC) L2 Study. Lung cancer cases and controls were recruited through a multicentric case-control study coordinated by the IARC in Russia, Poland, Serbia, Czech Republic, and Romania from 2005 to 2013. Cases were incident cancer patients collected from general hospitals. Controls were recruited from individuals visiting general hospitals and out-patient clinics for disorders unrelated to lung cancer and/or its associated risk factors, or from the general population. Information on lifestyle risk factors, medical and family history was collected from subjects by interview using a standard questionnaire. All study participants provided written informed consent. The current study included 1,133 lung cancer cases and 1,117 controls genotyped on the Oncoarray. The Washington State University Lung Cancer Study is a hospital case-control study of 511 subjects with newly-diagnosed (within 1 year of diagnosis) lung cancer and 820 race-, sex- and age-matched controls. Lung cancer cases were recruited from lung cancer clinics within the H. Lee Moffitt Cancer Center while controls were recruited from the Lifetime Cancer Screening Center, a H. Lee Moffitt Cancer Center affiliate. None of the controls were diagnosed with any form of cancer at the time of screening. Detailed questionnaire data and oral buccal cells were collected for all subjects. The Total Lung Cancer (TLC) Study is a hospital-based study that included 458 lung cancer patients recruited for Moffitt Cancer Center's Total Cancer Care™ protocol between April 2006 and August 2010. Total Cancer Care™ is a multi-institutional observational study of cancer patients that prospectively collects self-reported demographic and clinical data, medical record information and blood samples for research purposes. All patients used in this cohort were recruited from the Thoracic Oncology Clinic at the Moffitt Cancer Center. The Vanderbilt Lung Cancer Study (BioVU) is a case-control study nested within the Vanderbilt University Medical Center biobank, BioVU. BioVU is a biorepository of DNA extracted from blood drawn from patients seeking routine clinical care at Vanderbilt University Medical Center and linked to de-identified electronic health records for research purposes. Lung cancer cases and controls were identified from BioVU participants in February 2014. Lung cancer cases were identified from the Vanderbilt tumor registry. All specimens undergo pathologic review for determination of morphology. Coding of histology was based on SEER Program Coding Guidelines. Controls were randomly selected from BioVU participants, excluding cancer patients, and were matched to cases on age (± 5 years), sex, and race. Relevant covariates were identified from electronic health records using natural language processing. Genomic DNA was extracted based on a standard protocol.

  Study phs001273

• NHLBI TOPMed: Pulmonary Fibrosis Whole Genome Sequencing

  This is a set of cases diagnosed with idiopathic pulmonary fibrosis, a fatal interstitial lung disease. These cases were included in the TOPMed phase three studies. The planned study will compare these cases to within-TOPMed controls for genome-wide association studies.

  Study phs001607

• MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Colorectal

  he 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. 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.

  Study EGAS00001003774

• MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__Colorectal_LCM

  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. 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.

  Study EGAS00001003455

• MutWP1__CRUK_Grand_Challenge_Mutographs_of_Cancer__clear_cell_renal_cell_carcinoma___2

  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. 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.

  Study EGAS00001003542

• The dataset for Detection of brain cancer using genome-wide cell-free DNA fragmentomes

  The dataset for “Detection of brain cancer using genome-wide cell-free DNA fragmentomes” includes 310 bam files from whole genome next-generation sequencing on the Illumina Novaseq 6000. The dataset analyzed include plasma cfDNA samples from patients with cancer, patients with neurological conditions, and healthy individuals.

  Dataset EGAD50000001445

• Testing_the_feasibility_of_genome_scale_sequencing_in_routinely_collected_FFPE_cancer_specimens_versus_matched_fresh_frozen_samples

  Testing the feasibility of genome-scale sequencing in routinely collected formalin-fixed paraffin-embedded (FFPE) cancer specimens versus matched fresh-frozen samples using whole exome and targeted exome capture prior to Illumina sequencing.

  Study EGAS00001000173

• Integrated RNA-seq analysis of tumor thrombus

  We prospectively enrolled 83 patients with a renal mass and TT scheduled to undergo surgical resection. To accurately integrate genomic and transcriptomic findings and enable histological co-registration, simultaneous isolation of DNA and RNA was performed from individual samples characterized histologically through immediately flanking sections

  Study EGAS00001005512

• Whole Exome and RNA-Sequencing of Germline, Small Bowel Carcinoid Primary Tumor, and Liver Metastasis Trios

  This dataset includes trios of germline/constitutional, primary tumor (small bowel carcinoid), and metastatic tumor (liver) trios for 5 patients (i.e. 15 samples total). Constitutional, primary tumor, and metastatic tumor samples all underwent whole exome sequencing (WES or WXS). Primary and metastatic tumor samples underwent RNA sequencing (RNA-seq).

  Dataset EGAD00001010036

• Single-cell RNA-seq of cervical smears and early placental material

  Fastq files of single-cell RNA-sequencing data generated with 10X Genomics of twelve non-invasive cervical samples from pregnant women (7-12 weeks gestational age) and six placental biopsies from patients who had a recurrent miscarriage early during gestation (<12 weeks gestational age).

  Dataset EGAD00001010094

• Integrated analysis of whole genome and RNA sequencing in 22 HBV-associated HCCs

  RIKEN collection WGS and RNA-seq reads for 66 HBV-associated HCC and matched blood or liver samples from 22 donors.

  Dataset EGAD00001001035

• Using_genetics_to_identify_cell_types_and_mechanisms_underlying_susceptibility_to_primary_sclerosing_cholangitis

  Primary sclerosing cholangitis (PSC) is a T-cell mediated, chronic inflammatory condition of the biliary tree that is strongly associated with inflammatory bowel disease. Genome-wide association studies have identified 22 non-HLA genetic risk variants associated PSC. Identifying the genes impacted by these variants has proven difficult as the majority lie in non-coding regions of the genome. Knowledge of the genes and biological pathways these non-coding variants are perturbing is vital to understanding the disease biology. One means of assessing the impact of non-coding variants within disease associated loci upon genes is via colocalisation with eQTL. Many eQTL are cell-type specific, requiring the analysis of disease relevant cell types to detect colocalisation. We have collected PSC-relevant T-cell-subtypes from the peripheral blood of PSC patients via fluorescence activated cell sorting in preparation for RNA sequencing and mapping of eQTL. Samples were collected at the Norfolk and Norwich University Hopital, for which local ethical approval has been granted. Lysed cell samples will be transferred to WTSI and DNA/RNA will be extracted from lysed cell samples by T143 before genotyping (DNA) and custom library preparation and sequencing (RNA). 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 EGAS00001002643

• Using_genetics_to_identify_cell_types_and_mechanisms_underlying_susceptibility_to_primary_sclerosing_cholangitis

  Primary sclerosing cholangitis (PSC) is a T-cell mediated, chronic inflammatory condition of the biliary tree that is strongly associated with inflammatory bowel disease. Genome-wide association studies have identified 22 non-HLA genetic risk variants associated PSC. Identifying the genes impacted by these variants has proven difficult as the majority lie in non-coding regions of the genome. Knowledge of the genes and biological pathways these non-coding variants are perturbing is vital to understanding the disease biology. One means of assessing the impact of non-coding variants within disease associated loci upon genes is via colocalisation with eQTL. Many eQTL are cell-type specific, requiring the analysis of disease relevant cell types to detect colocalisation. We have collected PSC-relevant T-cell-subtypes from the peripheral blood of PSC patients via fluorescence activated cell sorting in preparation for RNA sequencing and mapping of eQTL. Samples were collected at the Norfolk and Norwich University Hopital, for which local ethical approval has been granted. Lysed cell samples will be transferred to WTSI and DNA/RNA will be extracted from lysed cell samples by T143 before genotyping (DNA) and custom library preparation and sequencing (RNA). 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 EGAS00001002642

• Genomic Origins and Admixture in Latinos (GOAL)

  The GOAL Study was designed to comprehensively evaluate the genomic architecture of diverse Hispanic/Latino individuals with origins from the Caribbean, Central and South America, and to understand the impact of this diversity on genetic disease studies. Population structure and admixture are key confounders in genome-wide association and medical resequencing studies. In particular, accounting for difference in ancestry among cases and controls, both in terms of genomic and geographic location, is critical for proper analysis and interpretation of studies with multi- and trans-ethnic samples. Genomic studies of Hispanics/Latinos, the largest and fastest growing minority group in the US, reveal that they are a highly genetically heterogeneous admixed group with immense variation among individuals and populations in the proportions of African, European, and Native American ancestry. Knowledge of the underlying complex genetic structure of US Hispanic/Latino and Caribbean populations is, therefore, essential to ensuring robustness of genotype-phenotype associations and understanding the medical relevance of associated variants across diverse populations in the US and throughout the Americas. Furthermore, since much is known about the African and European migrations into the Americas over the past 500 years, population genetic studies of Hispanics/Latinos serve as an excellent model for developing novel algorithms and approaches for characterizing fine-scale genetic structure of admixed populations, in general. This project extends current studies of population genetic structure in US Hispanics/Latinos by densely genotyping parent-offspring triads from individuals (sampled in the US) of Caribbean-descent from six Latin American countries: Puerto Rico, Cuba, Dominican Republic, Haiti, Honduras and Colombia. This study will provide immediate insights and new statistical methods to improve study design and genetic analysis for medical genomic studies in Hispanics/Latinos, other complex admixed groups, and multi- and trans-ethnic studies.

  Study phs000750

• DNA methylation database for gynecological cancer detection, classification and assay development

  MeD-seq data (fastq files) from gynecological cancers and associated healthy tissues. In total 292 fastq files generated by MeD-seq are deposited consisting of: healthy tissues (vulva n=11, cervix n=15, endometrium n=13, fallopian tube n=18 and ovary n=13), precursor lesions of cancer (vulva n=23 and cervix n=46) and cancer (vulva n=21, cervix n=45, endometrium n=26, fallopian tube n=8 and ovary n=33)

  Dataset EGAD50000000611

• To_profile_the_landscape_of_sebaceous_tumours___RNA

  Sebaceous tumours are a rare cutaneous cancer with potential for aggressive behaviour. However, limited information is available on these cancers with few published cases. Here we wish to exome sequence these cancers to define the first genomic landscape for this malignancy. We will extract RNA from formalin-fixed, paraffin-embedded (FFPE) cores. Cores may be obtained from lesional and non-lesional tissues of primaries as well as matching metastases. The extracted RNA will be used for RNA sequencing.

  Study EGAS00001007803

• Single-cell/single-nucleus RNA-seq of Embryonal Tumor with Multilayered Rosettes (ETMR)

  Embryonal tumor with multilayered rosettes (ETMR) is a pediatric brain tumor with dismal prognosis. We analyzed eleven ETMR patient samples using single-cell transcriptomics. We reveal a spatially distinct cellular hierarchy that spans highly proliferative neural stem-like cells and more differentiated neuron-like cells. C19MC is predominantly expressed in stem-like cells and controls a transcriptional network governing stemness and lineage commitment. Systematic analysis of receptor-ligand interactions between malignant cell types reveals FGFR and NOTCH signaling as oncogenic pathways. Our study provides fundamental insights into ETMR pathobiology and a powerful rationale for more effective targeted therapies.

  Study EGAS50000000937

• single cell data from HPV-positive head and neck cancer patients receiving induction CTLA-4 and PD-1 immune checkpoint blockade

  Baseline and on-treatment tumor samples from human papillomavirus-positive oropharynx cancer patients receiving anti-CTLA-4 and anti-PD-1 immune checkpoint blockade were analyzed by single-cell RNA and TCR sequencing.

  Study EGAS50000000335

• Dataset for GIST-EXON

  Rare cancer sequencing data of 64 runs in tumor/control pairs, which were uploaded to umbrella studies. The sequencing was always paired

  Dataset EGAD00001008875

• PDAC organoid genomic heterogeneity

  The establishment of patient-derived pancreatic cancer organoid culture in recent years creates an exciting opportunity for researchers to perform a wide range of in vitro studies on a model that closely recapitulates the tumor. Among the outstanding questions in pancreatic cancer biology are the causes and consequences of genomic heterogeneity observed in the disease. However, to use pancreatic cancer organoids as a model to study genomic variations, we need to first understand the degree of genomic heterogeneity and its stability within organoids. Here, we used single-cell whole-genome sequencing to investigate the genomic heterogeneity of two independent pancreatic cancer organoids, as well as their genomic stability with extended culture. Clonal populations with similar copy number profiles were observed within the organoids, and the proportion of these clones was shifted with extended culture, suggesting the growth advantage of some clones. However, sub-clonal genomic heterogeneity was also observed within each clonal population, indicating the genomic instability of the pancreatic cancer cells themselves. Furthermore, our transcriptomic analysis also revealed a positive correlation between copy number alterations and gene expression regulation, suggesting the “gene dosage” effect of these copy number alterations that translates to gene expression regulation.

  Study EGAS00001006782

• Transcriptome of CD4+ T cells and CD8+ T cells in glioblastoma multiforme

  Patients included in this study were over 18 years of age and had a histology-confirmed diagnosis of glioblastoma multiforme (GBM). Exclusion criteria were the previous administration of any anti-tumor therapy including radiation therapy. All patients gave written informed consent. The study was approved by the local ethics committee (TUM Medical school) and conducted following the Declaration of Helsinki. During resection of the tumors, tumor tissue and tissue from normal appearing brain within the operative channel was collected. Blood was drawn during the surgical procedure. Single cell suspensions were prepared from the tumor tissue, the normal appearing brain, and the blood. CD4+ T cells and CD8+ T cells were sorted by flow cytometry. Only patients with a complete set of specimens (CD4+ tumor infiltrating lymphocytes (TIL), CD8+ TIL, CD4+ T cells from normal appearing brain, CD8+ T cells from normal appearing brain, blood-derived CD4+ and CD8+ T cells) containing a minimum of 1000 cells in each sorted sample were further analyzed (n=9). Total RNA was isolated from sorted cell populations using the RNAeasy Plus micro kit (Qiagen, 74034). Quality and integrity of total RNA was controlled on a Bioanalyzer 2100 (Agilent Technologies). Library preparation for bulk-sequencing of poly(A)-RNA was done as described previously (Parekh et al., 2016). Briefly, barcoded cDNA of each sample was generated with a Maxima RT polymerase (ThermoFisher Scientific, EP0742) using oligo-dT primer containing barcodes, unique molecular identifiers (UMIs) and an adaptor. Ends of the cDNAs were extended by a template switch oligo (TSO) and full-length cDNA was amplified with primers binding to the TSO-site and the adaptor. NEB UltraII FS kit was used to fragment cDNA. After end repair and A-tailing, a TruSeq adapter was ligated and 3'-end-fragments were finally amplified using primers with Illumina P5 and P7 overhangs. In comparison to previous descriptions (Parekh et al., 2016), the P5 and P7 sites were exchanged to allow sequencing of the cDNA in read 1 and barcodes and UMIs in read 2 to achieve a better cluster recognition. The library was sequenced on a NextSeq 500 (Illumina) with 59 cycles for the cDNA in read 1 and 16 cycles for the barcodes and UMIs in read 2. Data were processed using the published Drop-seq pipeline (v1.0) to generate sample- and gene-wise UMI tables (Macosko et al., 2015). Reference genome (GRCh38) was used for alignment. Transcript and gene definitions were used according to the Genecode Annotation Version 35.

  Dataset EGAD50000000226

• Plasma-Seq follow-up CSPC4

  We performed serial plasma-Seq analyses on a male who progressed from castration-sensitive to castration-resistant prostate cancer within 10 months following treatment with androgen-deprivation therapy.

  Dataset EGAD00001000396

• Whole exome sequencing (WES), shallow whole genome sequencing (sWGS), ultra-deep targeted sequencing (TS), RNA whole transcriptome sequencing (RNAseq), targeted TCR sequencing in RNA (RNA-TCRseq) from breast cancer samples.

  Whole exome sequencing (WES), shallow whole genome sequencing (sWGS), ultra-deep targeted sequencing (TS), RNA whole transcriptome sequencing (RNAseq) bam files. Targeted TCR sequencing in RNA (RNA-TCRseq) cram files.

  Dataset EGAD00001003933

• Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma - RNA validation cohort

  This reposiroty contains bulk RNA data generated by Blood Cancer Research Group (Ostrava, Czech Republic) as a part of publication named "Elevated circulating tumor cells reflect high proliferation and genomic complexity in multiple myeloma" published in Hemapshere.

  Study EGAS50000001212

• Combination pembrolizumab and radiotherapy induces systemic anti-tumor immune responses in immunologically-cold non-small cell lung cancer

  This data set includes sequence files from whole exome sequencing and RNA sequencing from serial tissue and blood biospecimens from a phase 2 clinical trial of stereotactic body radiation therapy (SBRT) followed by pembrolizumab in metastatic non-small cell lung cancer (NSCLC; NCT02492568).

  Study EGAS50000000277

• EM-seq data from plasma cfDNA samples of ALS patients, control and C9-carriers

  This dataset contains targeted EM-seq data from 61 plasma cfDNA samples spanning 20 sporadic ALS, 10 C9orf72-ALS, 10 asymptomatic C9orf72 expansion carriers, and 21 non-disease controls. Libraries were prepared with the NEBNext Enzymatic Methyl-seq (EM-seq) kit, captured using the Twist Human Methylome Panel (3.98 M CpGs; 123 Mb), and sequenced on Illumina NovaSeq 6000 (150 bp paired-end; ~45× on-target depth) with unmethylated lambda DNA spike-in and a 20% PhiX balance library. The dataset includes per-sample gzipped FASTQ files (R1/R2) and minimal metadata.

  Dataset EGAD50000001808

• Risk and modifying factors in Frontotemporal Dementia

  Understanding the molecular mechanisms underlying frontotemporal dementia (FTD) is essential for the development of successful therapies. Here, we present Phase 1 of a multi-omics, multi-model data resource for FTD research which will allows in-depth molecular research into these mechanisms. We have integrated and analysed data from the frontal lobe of FTD patients with mutations in MAPT, GRN and C9orf72 and detected common and distinct dysregulated cellular pathways. Our results highlight that excitatory neurons are the most vulnerable neuronal cell type and that vascular aberrations are a common hallmark in FTD. Via integration of multi-omics data, we detected several transcription factors and pathways which regulate the strong neuroinflammation observed in FTD-GRN. Finally, using small RNA-seq data and verification experiments in cellular models, we identified several up-regulated miRNAs that inhibit cellular trafficking pathways in FTD and lead to microglial activation. In this work we shed light on novel mechanistic and pathophysiological hallmarks of FTD. In addition, we believe that this comprehensive, multi-omics data resource will further mechanistic FTD research by the community.

  Study EGAS00001004895

• AML Proteogenomic Landscape Whole-transcriptome RNA-Sequencing

  Whole transcriptome RNA-sequencing of purified bone marrow blasts of 136 de novo, treatment naive AML patients. For further details, we refer to the manuscript "The Proteogenomic Landscape of AML" by Jayavelu, Wolf, Buettner et al. mRNA extraction and whole transcriptome sequencing For transcriptome analysis the TruSeq Total Stranded RNA kit was used, starting with 250ng of total RNA, to generate RNA libraries following the manufacturer’s recommendations (Illumina, San Diego, CA, USA). 100bp paired-end reads were sequenced on the NovaSeq 6000 (Illumina) with a median of 57 mio. reads per sample. RNA Data Analysis Data quality control was performed with FastQC v0.11.9. Reads were aligned to the human reference genome (Ensembl GRCh38 release 82) using STAR v2.6.1. Gene count tables were generated while mapping, using Gencode v31 annotations. All downstream analyses were carried out using R v4.0 and BioConductor v3.12 (Huber et al., 2015; R Core Team, 2020). Size-factor based normalization was performed using DESeq2 v1.28.1(Love et al., 2014).

  Dataset EGAD00001008484

• Kidney_tumour_RNA

  This is a bulk DNA and RNA sequencing study of human renal tumours

  Study EGAS00001002487

• RaScALL: Rapid screening of RNA-seq in acute lymphoblastic leukaemia

  RNA-sequencing (RNA-seq) efforts in acute lymphoblastic leukaemia (ALL) have identified numerous prognostically significant genomic alterations which can guide diagnostic risk stratification and treatment choices when detected early. However, a full RNA-seq Bioinformatics workflow is time-consuming and costly in a clinical setting where rapid detection and accurate reporting of clinically relevant alterations are essential. To accelerate the identification of ALL-specific alterations (including gene fusions, single nucleotide variants and focal gene deletions), we developed the rapid screening tool RaScALL, capable of identifying more than 100 prognostically significant lesions directly from raw sequencing reads. RaScALL uses the k-mer based targeted detection tool km and known ALL variant information to achieve a high degree of accuracy for reporting subtype defining genomic alterations compared to standard alignment-based pipelines. Gene fusions, including difficult to detect fusions involving EPOR and DUX4, were accurately identified in 98% (164 samples) of reported cases in a 180-patient Australian study cohort and 95% (n=63) of samples in a North American validation cohort. Pathogenic sequence variants were correctly identified in 75% of tested samples, including all cases involving subtype defining variants PAX5 p.P80R (n=12) and IKZF1 p.N159Y (n=4). Accurate detection of intragenic IKZF1 deletions resulting in aberrant transcript isoforms was also detectable with 98% accuracy. Importantly, the median analysis time for detection of all targeted alterations averaged 22 minutes per sample, significantly shorter than standard alignment-based approaches, ensuring accerelated risk-stratification and therapeutic triage.

  Study EGAS00001006460

• Supraphysiologic MDM2 Expression Impacts P53-Independent Chromatin Networks and Therapeutic Responses in Sarcoma

  We collected multiple liposarcoma samples from different patients, including different subtypes (DD, WD) and normal adipose tissue as control. This study provides the biggest liposarcoma cohort to date, and examined the molecular regulatory circuits associated with MDM2 overexpression. To this end, we obtained not only RNA-seq data, but also ChIP-seq from Jun, RUNX, MDM2, P53 and H3K27ac, as well as hiChIP from tumor samples and cell lines. We found that MDM2 binds to thousands of genes involved in cellular growth and stress response in a P53-independent manner. Furthermore, we described these active genes engaged in multi-way topological interactions that resemble transcriptional hubs.

  Study phs003272

• Genome-wide chromatin accessibility profiling of primary human glomerular and kidney cortex tubular outgrowth cultures

  We generated primary cultures from mechanically isolated kidney glomeruli (filtration unit of the nephron) which are composed of podocytes and mesangial cells. In parallel, we generated primary kidney cortex tubule cell cultures, which are composed primarily of proximal tubule cells. Early passage cultures of these two cell types were subjected to chromatin accessibility profiling (DNase-Seq) and gene expression profiling (RNA-Seq). We found thousands of dynamically regulated enhancers in both cell types that potentially regulate nearby and distal target genes that are differentially expressed. These data will be useful for understanding the epigenomic regulation of gene transcription in key kidney cell types.

  Study phs001720

• NextGen Consortium: GENESiPS Study: Identifying the Gene Networks of Insulin Resistance

  Variability in induced pluripotent stem cell (iPSC) lines remains a roadblock for disease modeling and regenerative medicine. Through linear mixed models we have described different sources of gene expression variability from RNA sequencing data in 317 human iPSC lines from 101 individuals. We found that ~50% of genome-wide expression variability is explained by variation across individuals and identified a set of expression quantitative trait loci that contribute to this variation. These analyses coupled with allele specific expression show that iPSCs retain a subject-specific gene expression pattern. Pathway enrichment and key driver analyses, based on predictive causal gene networks, found that Polycomb targets explain a significant part of the non-genetic variability present in iPSCs within and across individuals. These publically available iPSC lines and genetic datasets will be a resource to the scientific community and will open new avenues to reduce variability in iPSCs and improve their utility in disease modeling. SNP array data from individuals included in RNA-seq transcriptome profiling study of human induced pluripotent stem cells to characterize gene expression variation across individuals and within multiple iPSC lines from the same individual. Genotyping was performed on patient blood. Data availability: SNP-genotyping: dbGaP - current study RNA-seq counts: GEO - GSE79636 FASTQ files: SRA - SRP072417

  Study phs001139

• RNA sequencing of primary B-cells infected with Epstein-Barr virus (EBV), treated with heat-inactivated EBV, CpG or BCR-crosslinking in presence or absence of Linrodostat

  B cells were isolated from buffy coat preparations of healthy donors using CD19 magnetic beads. B cells were then infected with EBV using spinoculation or activated with heat-inactivated EBV, respectively. Additionally cells were treated with 5ng/ml CpG or a BCR-crosslinking mixture in presence or absence of 10 µM Linrodostat (IDO1 inhibitor). RNA samples were isolated at 2 days post-infection / post-activation and one day 0 control with non-infected B cells was included.

  Dataset EGAD50000000306

• Identification of the cause of juvenile parkinsonism in a case_SYNJ1

  This study aimed to elucidate the genetic causes underlying the Juvenile Parkinsonism diagnosed in a girl using whole-exome sequencing, analysis of CAG repeats, RNA sequencing analysis on fibroblasts, and metabolite identification. As a result, a homozygous missense mutation SNP T/C (rs2254562) in SYNJ1 and alteration in metabolism were identified.

  Study EGAS00001007686

• Multiomic Dissection of Movement and Neurocognitive Toxicity Following BCMA-Targeting CAR T Therapy

  We report a case of parkinsonism following treatment with ciltacabtagene autoleucel. To investigate underlying mechanisms, we performed a multi-pronged longitudinal analysis using single-cell RNA/TCR-sequencing including both cerebrospinal fluid (CSF) and peripheral blood samples, spanning a time frame over 6 month after CAR T cell therapy.

  Study EGAS50000001634

• 112 "KOREAN" never-smoker female adenocarcinoma exome-seq

  All sequencing was performed within the DNAlink (Korea) by using the Solexa sequencing technology (Illumina, San Diego, CA). 1 ug of genomic DNA was sheared to an average size of 150 bp by using the Covaris System. The libraries were prepared by using TruSeq DNA Sample Prep Kit (Illumina). The purified DNA library was hybridized with the SureSelect Human All Exon V3 probe set (Agilent Technologies) to capture 50 Mb of targeted exons following the manufacturer’s instructions. Exome capture was carried out using the Agilent SureSelect Human All Exon 50Mb Kit. The captured exome libraries were sequenced on the Illumina HiSeq2000 using the manufacturer’s recommended protocols.

  Dataset EGAD00001005126

• Liquid biopsy to identify taxane resistance in castration-resistant prostate cancer patients

  Taxanes are life-prolonging treatments for patients with advanced prostate cancer. However, treatment resistance and lethal disease invariably develops. We here used liquid biopsies to identify and characterize resistance to cabazitaxel using a targeted sequencing panel (PCF-SELECT).

  Study EGAS50000001292

• Botensilimab, an Fc-enhanced Anti-CTLA-4 Antibody, is Effective Against Tumors Poorly Responsive to Conventional Immunotherapy

  This study explores the genomic landscape associated with a novel Fc-engineered anti-CTLA-4 antibody (botensilimab) in advanced solid tumors. We seek to understand if enhancing the Fc-region affinity of anti-CTLA-4 antibodies can improve anti-tumor efficacy and expand clinical benefit to tumors poorly responsive to conventional immunotherapy. As part of an ongoing open-label, Phase 1, multicenter study, we conducted an exploratory sub-analysis of genomics data. The primary study evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of botensilimab monotherapy and in combination with an anti-PD-1 antibody (balstilimab) in participants with advanced solid tumors. RNA from formalin-fixed paraffin-embedded (FFPE) tumor biopsies and matched normal blood samples were isolated and subjected to RNA-sequencing using the Personalis ImmunoID NeXT Platform. We demonstrated that anti-CTLA-4 engineered for enhanced FcγR affinity leverages FcγR-dependent mechanisms to potentiate T cell responsiveness, reduce intratumoral Tregs, and enhance antigen presenting cell activation. This genomic analysis contributes to our understanding of the molecular mechanisms underlying patient responses to Fc-engineered anti-CTLA-4 therapy and may inform future strategies to expand the clinical benefit of immune checkpoint blockade in cancer immunotherapy.

  Study phs003704

• Single cell RNAseq of PBMC from bladder cancer patients

  This dataset contains single cell RNA sequencing data of PBMC samples from 20 bladder cancer patients. cDNAs and single cell RNA libraries were prepared following manufacturer’s user guide (10x Genomics). Each library was sequenced in HiSeq4000 (Illumina) to achieve ~300 million reads following manufacturer’s sequencing specification.

  Dataset EGAD00001006182

• small RNA next generation sequencing in head and neck cancer

  small RNA next generation sequencing in head and neck cancer

  Dataset EGAD00001008402

• Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR)

  The Pediatric Investigation for Genetic Factors Associated with Renal Progression (PediGFR) (RO1-DK082394) is an international collaborative study among three large prospective cohort studies of children with chronic kidney disease. The participating parent cohort studies are the Chronic Kidney Disease in Children (CKiD), the Effect of Strict Blood Pressure Control and ACE Inhibition on CRF Progression in Pediatric Patients (ESCAPE), and the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study. In these cohorts, pediatric subjects with CKD have been prospectively followed with standardized measurements for renal progression. The dbGaP data upload will utilize the structure of sub-studies to include the genotype and baseline phenotype for the three cohorts, as well as the RBC trait and anemia data for a sub-study under PI Susan Furth: Role of Genetic Variation in the Anemia of Chronic Kidney Disease (K24DK078737). In brief PediGFR is a prospective study of children with chronic kidney disease (CKD) to determine genetic factors associated with kidney function measured by the estimated glomerular filtration rate (eGFR) by Schwartz equation. The PediGFR_v2 Cohort is utilized in the following dbGaP sub-studies. To view genotypes, other molecular data, and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" box located on the right hand side of this top-level study page phs000842 PediGFR_v2 Cohort. phs000843 4C phs000650 CKiD phs000844 ESCAPE

  Study phs000842

• circulating cell-free RNAs, CF-miRNAs, Sequencing with Qiaseq and NextSeq 550

  This dataset includes small RNA sequencing data from circulating cell-free RNAs (CF-miRNAs). miRNA libraries were prepared using the Qiaseq miRNA Library Kit with adaptations for low RNA input and sequenced on the Illumina NextSeq 550 platform

  Dataset EGAD50000001503

• Single cell RNA sequencing of CD34+ CB and BM samples in SLE and healthy controls

  Single cell RNA paired-end sequencing was performed on CD34+ progenitor cells derived from 4 SLE patients, 6 healthy control samples and 2 umbilical cord blood samples using Illumina MiSeq/NextSeq 500.

  Dataset EGAD00001011277

• Single-cell proteogenomics of MDS upon AZA

  To study the evolution of the clonal molecular and cellular architecture of MDS upon the treatment with AZA, we performed scDNA-seq of an amplicon panel of 53 genes recurrently mutated in myeloid malignancies, as well as typically lost or gain DNA regions, and scProt-seq of 42 cell-surface proteins to provide a simultaneous landscape of the genetic setting and immunophenotype using the Tapestri platform (MissionBio). We sequenced thousands of cells from 14 MDS patients, where paired bone marrow samples were obtained at the timepoint of diagnosis and after AZA treatment.

  Study EGAS00001007427

• cfDNA methylation dataset for colon cancer

  Enzymatic conversion-based methylation sequencing data (EM-seq) for colon cancer used in the MESA study

  Dataset EGAD50000000075

• Reconstructed BCRs

  Computationally reconstructed B-cell receptor sequences (using BraCeR) from scRNA-seq data for all cells passing quality control.

  Dataset EGAD00001008456

• Human Blastocyst 10X Single Cell RNA Sequencing

  Recent advances in human blastoids have opened new avenues for modeling early human development and implantation. One limitation of our first protocol for human blastoid generation was relatively low efficiency. We now report an optimized protocol for the efficient generation of large quantities of high-fidelity human blastoids from naive pluripotent stem cells. This enabled proteomics analysis that identified phosphosite-specific signatures potentially involved in the derivation and/or maintenance of the signaling states in human blastoids. Additionally, we uncovered endometrial stromal effects in promoting trophoblast cell survival, proliferation, and syncytialization during co-culture with blastoids and blastocysts. Side-by-side single-cell RNA sequencing revealed similarities and differences in transcriptome profiles between pre-implantation blastoids and blastocysts, as well as post-implantation cultures, and uncovered a population resembling early migratory trophoblasts during co-culture with endometrial stromal cells. Our optimized protocol will facilitate broader use of human blastoids as an accessible, perturbable, scalable, and tractable model for human blastocysts. In addition, this study is the first to use the 10X Genomics platform for human blastocysts, and we anticipate this resource will be widely used by the community as a reference for future studies.

  Study phs003122

• Single-cell RNA-seq from tumor-on-chip (TOC)

  8 Fastq files of single-cell RNAseq data from tumor-on-chip (TOC) after 42h of TNBC and CAF mono- or co-culture

  Dataset EGAD50000001296

• Pineoblastoma Single-Nuclei RNA-seq Data Access Committee (St. Jude)

  Committee responsible for reviewing and approving external access requests to controlled-access pediatric brain tumor transcriptomic datasets from St. Jude Children's Research Hospital, ensuring alignment with patient consent and institutional ethics policies.

  Dac EGAC50000000839

• Esophageal Adenocarcinoma Organoid scRNAseq data

  This is 10X single cell RNA-seq data of esophageal adenocarcinoma organoids.

  Dataset EGAD00001007525

• 2_cortical-neurons_HD_vs_Ctrl_DMSO_Branaplam

  n=3 Ctrl and n=3 HD iPSC lines differentiated into cortical neurons were treated with DMSO or 10nM Branaplam for 72h and RNA-seq was performed.

  Dataset EGAD00001008808

• Human Epidermis scRNA

  Single cell RNA-seq analysis of human skin.

  Dataset EGAD00001004367

• smMIP-seq of 18 FFPE prostate samples (normal and tumour pairs) to identify mutations

  smMIP-Seq was performed on radical prostatectomy formalin-fixed paraffin-embedded sample pairs (n = 18). Library prep was done by capture of targeted sequences with single molecule (unique molecular index) tagged molecular inversion probes (MIP) and sequenced as 75bp paired end on Illumina NextSeq 500. Sequences were aligned to the human genome (hg38) using BWA.

  Dataset EGAD00001006109

• Evaluation of somatic mutations in urine samples as a non-invasive method for the detection and molecular classification of endometrial cancer

  Purpose: Current diagnostic methods for endometrial cancer lack specificity, leading to many women undergoing invasive procedures. The aim of this study was to evaluate somatic mutations in urine to accurately discriminate endometrial cancer patients from controls. Experimental Design: Overall, 72 samples were analyzed using next-generation sequencing with molecular identifiers targeting 47 genes. We evaluated urine supernatant samples from women with endometrial cancer (n=19) and age-matched controls (n=20). Cell pellets from urine and plasma samples from seven cases were sequenced; further, we also evaluated paired tumor samples from all cases. Finally, immunohistochemical markers for molecular profiling were evaluated in all tumor samples. Results: Overall, we were able to identify mutations in DNA from urine supernatant samples in 100% of endometrial cancers. In contrast, only one control (5%) showed variants at a variant allele frequency (VAF)≥2% in the urine supernatant samples. The molecular classification obtained by using tumor samples and urine samples showed good agreement. Analyses in paired samples revealed a higher number of mutations and VAFs in urine supernatants than in urine cell pellets and blood samples. Conclusions: Evaluation of somatic mutations using urine samples may offer a user-friendly and reliable tool for endometrial cancer detection and molecular classification. The diagnostic performance for endometrial cancer detection was very high, and cases could be molecularly classified using these noninvasive and self-collected samples. Additional multi-center evaluations using larger sample sizes are needed to validate the results and understand the potential of urine samples for the early detection and prognosis of endometrial cancer.

  Study EGAS00001007396

• Prime-seq of human term placenta-derived trophoblast organoids

  To study the one of the mechanisms through which obesity could affect placental cells, we used a novel microfluidic organs-on-a-chip device fabricated for co-culturing adipose spheroids and trophoblast organoids. The organoids were derived from the term placenta of a over-weight women. The adipose spheorids were derived from the white adipose tissue of a woman. And we sequenced the RNAs from the trophoblast organoids. The RNA extracted were subjective to Prime-seq library preparation protocol and being sequenced on Illumina NovaSeq 6000 at Novogene.

  Study EGAS50000000833

• 300BCG study: human population variation of trained immunity

  To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live attenuated vaccine induces not only an adaptive immune response against tuberculosis, but also triggers innate immune activation and memory. We established personal chromatin accessibility maps over a time course of BCG vaccination in the 300BCG cohort using ATAC-seq.

  Study EGAS50000000090

• 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

• Separation, characterization, and identification of individuals from multi-person blood mixtures with single cell transcriptome sequencing and a novel bioinformatics pipeline

  We report a deconvolution and identification strategy of scRNA-seq datasets using mixed PMBCs data. After sequencing the data were processed with the de-goulash pipeline and analyzed with aim to identify and aquire biogeogrpahical ancestry of the involved individuals. The study includes samples of biological mixtures and in silico mixtures.

  Study EGAS00001006202

• Cambridge COVID-19 Single-cell PBMC

  Single-cell multi-omic profiling of healthy controls, asymptomatic and hosptial-admitted COVID19 patients recruited from Addenbrookes and Royal Papworth hospitals, in collaboration with the NIHR Cambridge Bioresource. Data represent RNA-seq, surface protein measurements (CITE-seq) of 192 antibody targets, along with VDJ-seq profiling of single T cell and B cell receptors. Samples are pooled, with 4 donors per pool. Germ-line genotypes are provided (VCF) to aid demultiplexing of single-cell and assignment to specific patient donor samples.

  Dataset EGAD00001007867

• DNA WGS Long Read Sequence (PromethION) for manuscript titled: "Performance of Somatic Structural Variant Calling in Lung Cancer using Oxford Nanopore Sequencing Technology"

  DNA WGS Long Read Sequence (PromethION) for manuscript titled: "Performance of Somatic Structural Variant Calling in Lung Cancer using Oxford Nanopore Sequencing Technology"

  Dataset EGAD00001015400

• Baylor College of Medicine Advancing Sequencing in Childhood Cancer Care (BASIC3) Clinical Exome Sequencing Study - Clinical Sequencing Exploratory Research Consortium

  The BASIC3 (Baylor College of Medicine Advancing Sequencing in Childhood Cancer Care) study is a National Genome Human Research Institute (NHGRI) and National Cancer Institute-funded Clinical Sequencing Exploratory Research (CSER) consortium project that focuses on prospective implementation of clinical whole exome sequencing in the pediatric oncology clinic. The primary study objective are to integrate information from CLIA-certified germline and tumor exome sequencing into the care of newly diagnosed solid tumor patients at Texas Children's Cancer Center, and to perform parallel evaluation of the impact of tumor and germline exomes on families and physicians. Blood and frozen tumor (if available) samples are collected from children undergoing surgery or biopsy of newly diagnosed solid tumors and subjected to exome sequencing in a CLIA-certified laboratory. Germline and tumor (if applicable) exome sequencing reports are generated and submitted into the electronic health record and returned to each patient/family by their primary oncologist. If specific (optional) consent is obtained, research sequencing studies (including transcriptome sequencing) are performed in addition to the clinical exome sequencing.

  Study phs001026

• Aggregated panel-seq VCF for initial cohort screened for BoB

  Aggregated VCF file from cancer genes panel seq for the initial (n=500) cohort of solid tumors screened for the Basket of Baskets study

  Dataset EGAD00001008437

• The dataset for Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers

  The dataset for “Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers” includes 409 cram files from whole genome next-generation sequencing on the Illumina HiSeq2500. The samples analyzed include plasma samples from healthy individuals and patients with cancer.

  Dataset EGAD50000000695

• RNA sequencing of serial samples from patients enrolled in the NA-PHER2 trial

  Improved outcomes in HER2+ breast cancer have resulted from chemotherapy and anti-HER2 therapies. However, HER2+ER+ cancers exhibit lower response rates. The NA-PHER2 trial investigated chemo-free preoperative HER2 and CDK4/6 blockade with or without endocrine therapy in HER2+ER+ breast cancer. Through RNA sequencing and tumour infiltrating lymphocytes (TIL) assessment in serial biopsies we identified predictive biomarkers of pCR, Day 14 Ki67 response, and unveiled treatment-induced molecular changes.

  Study EGAS50000000248

• Childhood Cancer Model Atlas

  we establish a single-site collection of 243 cell lines, including 207 paediatric cancer cell lines representing 14 distinct extracranial and brain childhood tumour types. We subjected 164 paediatric cancer cell lines to multi-omic analyses across three dimensions (DNA-sequencing, RNA-sequencing, DNA methylation) to classify them based on clinically relevant molecular subtypes.

  Study EGAS00001006320