14977 results for "cancer studies using rna-seq"

in 35.97 milliseconds.

• Genome Instability in Mammary Cells of Pathogenic BRCA1/2 Mutation Carriers

  It remains unknown if inherited germline mutations in the BRCA1 or BRCA2 gene increase the risk of breast and ovarian cancer by elevating mutation rate in mammary cells. Here we show, using a single-cell whole genome sequencing approach, that mammary luminal epithelial cells isolated from tissues obtained from preventive mastectomy surgeries in women with a pathogenic BRCA1/2 germline mutation, exhibit a statistically significant, increased mutation frequency as compared to age-matched controls without genetic risk of breast cancer.

  Study phs002411

• Rapid Acceleration of Diagnostics - Underserved Populations (RADx-UP) Collection of General Research Use Datasets

  This individual-level collection of datasets contains all the RADx Underserved Populations (RADx-UP) studies in dbGaP for General Research Use (GRU) and have no further limitations beyond those outlined in the model RADx Data Use Certification Agreement. Access to this study collection will include additional authorized individual-level GRU datasets that become available. Renewal of this study collection is required annually. Access to studies in this collection is on the RADx® Data Hub. To request access to this study collection, select phs003832 in the dbGaP when submitting a data access request.

  Study phs003832

• Rapid Acceleration of Diagnostics - Tech Program (RADx-Tech) Collection of General Research Use Datasets

  This individual-level collection of datasets contains all the RADx® Tech Programs (RADx-Tech) studies in dbGaP for General Research Use (GRU) and have no further limitations beyond those outlined in the model RADx Data Use Certification Agreement. Access to this study collection will include additional authorized individual-level GRU datasets that become available. Renewal of this study collection is required annually. Access to studies in this collection is on the RADx® Data Hub. To request access to this study collection, select phs003831 in the dbGaP when submitting a data access request.

  Study phs003831

• Rapid Acceleration of Diagnostics - Radical (RADx-rad) Collection of General Research Use Datasets

  This individual-level collection of datasets contains all the RADx® Radical (RADx-rad) studies in dbGaP for General Research Use (GRU) and have no further limitations beyond those outlined in the model RADx Data Use Certification Agreement. Access to this study collection will include additional authorized individual-level GRU datasets that become available. Renewal of this study collection is required annually. Access to studies in this collection is on the RADx® Data Hub. To request access to this study collection, select phs003834 in the dbGaP when submitting a data access request.

  Study phs003834

• Targeted re-sequencing of multi-region sampled tumors in PDAC

  Multi-region tumor samples were cut from frozen sections or FFPEs and reviewed from microdissection and H&E staining in order to select ones with high cellularity. DNA extraction was done using DNeasy Blood & Tissue Kits for frozen samples following the manufacturer’s guideline. Extracted DNAs were processed on an Illumina HiSeq 2500 in a paired end mode (100x100) using a custom targeted panel based on the list of all unique somatic mutations from the original WES data by the Integrated Genomics Operation (IGO) at Memorial Sloan Kettering Cancer Center (New York, NY).

  Study EGAS50000000239

• Clonally heritable gene expression imparts a layer of diversity within cell types

  Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells of the same type has been ascribed to stochastic transcriptional bursting and transient cell states. Using high coverage single cell RNA profiling, we asked whether long-term, heritable differences in gene expression can impart diversity within cells of the same type. Studying clonal human lymphocytes and mouse brain cells, we uncovered a vast diversity of heritable gene expression patterns among different clones of cells of the same type in vivo. We combined chromatin accessibility and RNA profiling on different lymphocyte clones to reveal thousands of regulatory regions exhibiting interclonal variation which could be directly linked to interclonal variation in gene expression. Our findings identify a source of cellular diversity, which may have important implications for how cellular populations are shaped by selective processes in development, aging and disease.

  Study EGAS50000000161

• Genetics of gene expression in primary human immune cells

  The purpose of this study was to identify cell specific expression quantitative trait loci in freshly isolated highly purified primary B-cells and monocytes from healthy subjects of European ancestry. Cells were purified from Ficoll gradient prepared peripheral blood mononuclear cell fractions using positive selection via magnetic bead labelling of the B-cell marker CD19 and monocyte marker CD14. RNA was extracted from 287 B-cell samples and 288 monocyte samples. RNA was then hybridised to HumanHT-12 v4 BeadChips whole genome expression arrays (Illumina). Individuals were genotyped on HumanOmniExpress-12v1.0 BeadChips (Illumina) at 733202 genetic markers. Data presented include the raw expression values and Robust Spline Normalised values (RSN) for expression for each cell type per individual. Additional genotype data per individual is available on request.

  Study EGAS00000000109

• Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma

  Background:Malignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. This study focuses on molecular intra-tumor heterogeneity using the largest series to date in MPM and is the first to report on the multi-omics profiling of a substantial series of multi-site tumor samples. Methods:Intra-tumor heterogeneity was investigated in 16 patients from whom biopsies were taken at distinct anatomical sites. The paired biopsies collected from apex, side wall, costo-diaphragmatic or highest metabolic sites as well as 5 derived cell lines were screened using targeted sequencing. Whole exome sequencing, RNA sequencing, and DNA methylation were performed on a subset of the cohort for deep characterization. Molecular classification, recently defined histo-molecular gradients, and cell populations of the tumor microenvironment were assessed. Results:Sequencing analysis identified heterogeneous variants notably in NF2, a key tumor suppressor gene of mesothelial carcinogenesis. Subclonal tumor populations were shared among paired biopsies, suggesting a polyclonal dissemination of the tumor. Transcriptome analysis highlighted dysregulation of cell adhesion and extracellular matrix pathways, linked to changes in histo-molecular gradient proportions between anatomic sites. Methylome analysis revealed contribution of epigenetic mechanisms in two patients. Finally, significant changes in the expression of immune mediators and genes related to immunological synapse, as well as differential infiltration of immune populations in the tumor environment were observed and led to a switch from a hot to a cold immune profile in three patients. Conclusions:This comprehensive analysis reveals patient-dependent spatial intra-tumor heterogeneity at the genetic, transcriptomic and epigenetic levels and in the immune landscape of the tumor microenvironment. Results support

  Study EGAS00001005328

• Ewing and Ewing-like-sarcoma tumoroid biobank reveals distinct drug sensitivities: translocation makes the difference

  Ewing sarcoma (ES) and Ewing-like sarcomas (ELS) are highly aggressive tumors found in soft tissues and bone of mostly children and young adults. Despite being different in many aspects, including genetics, possible cell-of-origin, and pathology, patients with any of these entities all receive the same therapeutic regimen. Currently, there is a lack of preclinical cell models that can predict drug response of these entities in vitro. Here, we describe a pediatric ES and ELS tumor organoid (tumoroid) biobank containing tumoroids with different translocations, including EWSR1::FLI1, EWSR1::ERG, CIC::DUX4, and BCOR-rearrangements. Using histology, whole genome sequencing and RNA sequencing, we demonstrate that these tumoroids retain key properties of their matching patient tumors. In addition, we traced tumor subclones in the tumoroids across patient-matched longitudinal samples, which showed that cellular heterogeneity was maintained. We subsequently performed drug screening on the tumoroid models, which unveiled entity-specific drug sensitivity to various cytotoxic compounds and targeted compounds, including MCL-1 inhibitors for CIC::DUX4 sarcomas. Taken together, this newly established ES and ELS patient-derived tumoroid biobank generates a unique source of material for future basic cancer research and drug-screening.

  Study EGAS00001007941

• Single-cell RNA sequencing of 16 NPM1 mutated AML patients

  NPM1 mutated AML is the largest class in WHO classification, however several subtypes within NPM1 were already reported. Here, we sequence 16 NPM1 mutated AML samples with single-cell RNA-sequencing and multi-color flow cytometry from three major NPM1 subtypes we previously identified, totaling more than half a million cells. We show that the differences among three NPM1 subtypes are mainly driven by cell composition, and these differences are also reflected at cell surface protein level. With the re-analysis of CITE-seq data from another cohort and single cell variant calling on our data, we also report two distinct stem cell phenotypes: one with leukemic (CD34dimCD38-CD45RA+) and another with pre-leukemic (CD34+CD38-CD45RA-) origin. We believe that our data and findings provide novel insights regarding the etiology of NPM1 mutated AML.

  Study EGAS50000000332

• Lymphocyte_LCM_WGS

  Using whole genome sequencing of lymphocytes excised from human tissue using laser capture microscopy (LCM), we identify the mutations arising in these microenvironments. This work will contribute towards developing a catalogue of mutations present in tissue resident lymphocytes across a range of tissues, and will characterize the mutational signatures that result from each microenvironment.

  Study EGAS00001003384

• Liquid Biopsy Detection of Tumor-specific Structural Variants in High Grade Serous Ovarian Cancer

  WGS Liquid Biopsy. Recurrence is frequent for most patients with high grade serous ovarian cancer (HGSOC), even after effective chemotherapy induced remission. However, after achievement of complete clinical response, the minimal residual disease is often insufficient for genomic analysis. Therefore, methods to interrogate the clonal composition and molecular properties of minimal residual disease are needed to better understand the mechanisms of HGSOC relapse. To address this unmet need, we developed and validated a novel cfDNA-based approach for tracking disease burden using NGS-informed tumor specific structural variants (SVs). Methods: The optimization of the methodology was first performed using synthetic cfDNA generated by ultrasonication of gDNA from ovarian cancer cell lines. Following the optimized workflow, whole genome sequencing of multisite biopsies from pre-treatment HGSOC patients were performed and high confidence SVs were called by consensus of multiple published SV callers. Real-time PCR and digital droplet PCR (ddPCR) were used for assays development.

  Study EGAS50000001044

• Characterization of CNS Metastases

  Metastatic disease to the central nervous system (CNS) is devastating, with a poor prognosis. There are limited treatment options for patients with CNS metastases, and in particular with leptomeningeal carcinomatosis (LMD). In this study, we evaluated the molecular and cellular features of parenchymal brain metastases and LMD. We used single-cell RNA and cell-free DNA profiling of CSF from patients with LMD receiving immunotherapy to demonstrate shifts in the liquid LMD tumor microenvironment. We also characterize the tumor microenvironment of parenchymal brain metastases using single cell sequencing, before and after treatment with immunotherapy.

  Study phs002416

• Characterization of the molecular signature of human monocytes in aging and myelodysplastic syndrome

  Deep immunophenotypic profiling of peripheral blood immune cells from young and older control subjects as well as patients with MDS was initially performed, using mass cytometry to identify monocyte subpopulations. Abundance of monocyte subpopulations separated the samples from patients with MDS from elderly control subjects was identified. Therefore, targeted immunophenotyping of monocytes was also performed with flow cytometry and RNA sequencing from isolated CD14+ peripheral blood longitudinally in 26 subjects, six young healthy individuals, nine older healthy individuals and eleven patients with MDS.

  Study EGAS00001007676

• Epigenetic landscape reorganization and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma

  Accurate grading of IDH-mutant gliomas is crucial for determining patient prognosis and guiding treatment decisions. However, histological grading can be challenging, so we aimed to identify objective molecular markers. To this end, we conducted bulk RNA sequencing on primary IDH-mutant astrocytomas (n=138) from the prospective CATNON trial, which evaluated the prognostic impact of adjuvant and concurrent temozolomide. Using this data, we sought to identify molecular markers linked to increased malignancy in IDH-mutant astrocytomas to establish objective grading criteria.

  Study EGAS50000000381

• RNAseq data from human colon organoid infected by KP

  The aim of this study is to identify the specific bacteria that are responsible for pathological bacterial translocation and subsequent Th17 priming in the liver in primary sclerosing cholangitis (PSC). To clarify the mechanism of how microbiota interacts with the intestinal epithelial barrier, monolayered human intestinal organoids were cultured with the specific bacteria. Gene expression analysis using RNA sequencing in epithelial cells cultured with Klebsiella pneumoniae derived from a PSC patient (KP-P1) or commercially obtained Klebsiella pneumoniae strain (KP JCM1662) was performed in this study.

  Study EGAS00001003332

• Mapping genetic variants that underlie gene regulation in intestinal cell types to identify novel, validated, Crohn’s disease drug targets

  Biopsies from the terminal ileum and rectum of healthy individuals and terminal ileum and blood from Crohns disease patients are collected and processed single cells and processed for single-cell RNA-sequencing using 10X Genomics 3' v3 and v3.1 and Illumina sequencing. 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 EGAS00001003647

• NHLBI TOPMed: Pediatric Cardiac Genomics Consortium (PCGC)'s Congenital Heart Disease Biobank

  The Pediatric Cardiovascular Genetics Consortium (PCGC) proposes to define genetic causes for congenital heart defects (CHD) as part of the TOPMed Program are the most common form of heart disease in childhood and are also the most prevalent form of birth defects, occurring in 2-3% of live births. The PCGC has recruited and clinically characterized = 10,000 CHD probands and parents (CHD trios). From whole exome sequencing (WES) of >2800 CHD trios, we identified a substantial enrichment of damaging de novo mutations in genes important for cardiogenesis, particularly implicating histone modifier enzyme gene defects. Analysis of whole genome sequencing (WGS) of 350 probands with CHD unexplained by WES and their parents preliminarily implicated de novo mutations in enhancers of genes previously shown to cause CHD in mouse knock out models. Sequencing of RNA (RNAseq) from discarded cardiac tissues from CHD probands has revealed likely causal allele-specific expression (ASE) as well as biallelic loss of expression (LOE). We have also discovered de novo epimutations, differentially methylated regions (DMRs), some with underlying de novo DNA variation, that are detectable in peripheral blood leukocytes and appear to underlie 10% of CHD. Of note, these assorted 'omic' approaches have enabled one another, both for attributing causality and assessing functional impact. Based on these extensive preliminary data, we hypothesize that PCGC probands with uninformative exomic analyses (WES-negative) harbor de novo genetic and/or epigenetic mutations in critical regulatory elements that participate in developmental expression of cardiac genes. To identify these etiologies, we propose analyses of WGS in 1000 WES-negative CHD trios, prioritizing those with probands with banked CHD tissues (n=78), one damaging variant in a recessive CHD gene, and older fathers (age>45). We also request WGS for 230 probands, for whom we have cardiac tissues but not parental DNAs. We request RNAseq for 308 cardiac tissues. For DNA methylation, which TOPMed will offer through the Illumina 850k array platform, we are requesting analysis of DNAs from peripheral blood leukocytes for all probands for whom WGS will be performed (1000 from trios, 230 singletons) as well as DNAs from cardiac tissues (n=308) to pair with the WGS, RNAseq and blood DNA methylation data. We will use existing resources and capabilities of the PCGC to confirm relevant mutations and those of its companion consortium in the Bench to Bassinet Program, the Cardiovascular Development Consortium, to inform analyses of non-coding mutations as well as to perform confirmatory functional genomics studies using cell and animal models. We expect that the studies resulting from data generated through TOPMed will provide novel insights into the molecular basis for CHD and fundamental knowledge about genes and pathways involved in cardiac development. Aside from being relevant to CHD, we anticipate that our findings will inform the understanding of later-onset cardiovascular diseases, including some arising in adulthood.

  Study phs001735

• Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer

  Background: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited. Objective: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC by tumour RNA sequencing, and to determine their association with overall survival (OS).

  Study EGAS50000001269

• Comprehensive molecular profiling of high-grade serous ovarian cancer

  The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC) is not well understood. Here, we performed comprehensive molecular analysis, including high-pass whole genome sequencing, targeted deep sequencing, RNA sequencing, reverse phase protein arrays and immune assessment, on primary and metastatic sites from highly clinically annotated HGSC samples. Samples were obtained pre-treatment based on a laparoscopic triage algorithm from patients who underwent R0 tumor debulking, or received neoadjuvant chemotherapy (NACT) with excellent or poor response.

  Study EGAS00001003804

• Functional Variant rs9344 at 11q13.3 Regulates CCND1 Expression in Multiple Myeloma with t(11;14)

  Multiple myeloma (MM) is a plasma cell (PC) malignancy characterized by cytogenetic abnormalities, such as t(11;14)(q13;q32), resulting in CCND1 overexpression. The rs9344 G allele within CCND1 is the most significant susceptibility allele for t(11;14). We have found the G risk allele is enriched in both healthy individuals of African ancestry and African American individuals with MM. The overall aim of this study was to identify the mechanism behind why the G allele is enriched in t(11;14) MM. To reach this goal, we performed ATAC-seq from 100,000 CD138+ tumor cells from 26 patients with MM. In addition, we performed ChIP-seq using antibodies against H3K4me1, H3K27ac and H3K4me3 from 100,000 CD138+ tumor cells from 8 patients with MM. We used these data to evaluate whether the G allele of rs9344 is associated with elevated chromatin accessibility, H3K27ac and H3K4me3 in t(11;14) MM.

  Study phs003997

• Whole-genome sequencing of normal Singaporean volunteers

  Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, along with questionnaire responses and multi-modal phenotypic data generated from 482 normal volunteers. First, we compared wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived TST. Among others, male gender (β = -15.539, 95% confidence interval [CI] = -26.245 - -4.832, p = 0.005), older age (β = -0.493, CI = -0.941 - -0.044, p = 0.032) and manual labor (β = -26.856, CI = -49.715 - -3.997, p = 0.022) were associated with reduced TST, whereas alcohol consumption (β = 19.247, CI = 8.008 - 30.486, p = 8.54x10-04) was associated with increased TST. Multi-modal phenotypic data analysis showed that wearable-derived TST and SE were associated with various cardiovascular disease risk markers such as body mass index (β = -0.006, CI = -0.00 - -0.000, p = 0.040) and waist circumference (β = 0.001, CI = -0.015-0.017, p = 0.893), whereas self-reported measures were not. We then showed that insufficient sleep was associated with premature telomere attrition, using telomere length estimated using whole-genome sequencing (β = 1.275, CI = 0.187 - 2.363, p = 0.023) and quantitative PCR (β = 0.001, CI = 8.318x10-05 - 0.001, p = 0.028). Our study highlights the potential for sleep metrics from consumer wearables to provide novel insights into data generated from population cohort studies.

  Study EGAS00001004007

• Low-coverage whole genome sequencing for a highly selective cohort of severe COVID-19 patients

  Background Despite advances in identification of genetic markers associated to severe COVID-19, the full genetic characterisation of the disease remains elusive. Imputation of low-coverage whole genome sequencing (lcWGS) has emerged as a competitive method to study such disease-related genetic markers as they enable genotyping of most common genetic variants used for genome wide association studies. This study aims at exploring the potential use of imputation in lcWGS for a highly selected severe COVID-19 patient cohort. Findings We generated an imputed dataset of 79 variant call format (VCF) patient files using the GLIMPSE1 tool, each containing, on average, 9.5 million single nucleotide variants. The validation assessment of imputation accuracy yielded a squared Pearson correlation of approximately 0.97 across sequencing platforms, showing that GLIMPSE1 can be used to confidently impute variants with minor allele frequency up to approximately 2% in Spanish ancestry individuals. We conducted a comprehensive analysis on the patient cohort, examining hospitalisation and intensive care utilisation, sex and age-based differences, and clinical phenotypes using a standardised set of medical terms specifically developed to characterise severe COVID-19 symptoms for this cohort. Conclusion This dataset highlights the utility and accuracy of lcWGS imputation in the study of COVID-19 severity, setting a precedent for other applications in resource-constrained environments. The methods and findings presented here may be leveraged in future genomic projects, providing vital insights for health challenges like COVID-19.

  Study EGAS00001007573

• Genomic DNA of tumor tissues, adjacent normal tissues, and peripheral blood were extracted using QIAamp DNA mini Kit (QIAGEN, cat. #51306)

  Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single cell resolution. Using optimized single cell multiomics sequencing together with multiregional sampling of the primary tumor, lymphatic and distant metastases, we provide insights beyond intratumoral heterogeneity. Genome wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 sequenced patients. The cancer cells’ DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue, and those of repetitive element Long Interspersed Nuclear Element 1. Our work demonstrates the feasibility of reconstructing genetic lineages, and tracing their epigenomic and transcriptomic dynamics with single cell multiomics sequencing.

  Study EGAS00001003242

• Highly complex single-cell mixture of 5 individuals of high cell number

  Mixture of 5 unrelated individuals sequenced by 10x as a scATAC-seq. The dataset was then processed by Cell Ranger and deconvoluted to yield each individuals genetic profile using the De-goulash pipeline. The separation file is submitted as the processed file. The bam are submitted as unprocessed files.

  Dataset EGAD50000000480

• scRNA-seq of first and second trimester human gonads - HUGODECA dataset

  Comprehensive map of first- and second-trimester gonadal development in humans using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays, and imaging. ArrayExpress Accession: E-MTAB-10551

  Dataset EGAD00001009386

• Transcriptomic characterization of the histopathological growth patterns in breast cancer liver metastases

  20 fastq files of RNA-sequencing of the 2 main histopathological grow patterns observed in liver metastases.

  Dataset EGAD50000000331

• Transcriptome data of WS patients and controls

  Fibroblasts of 4 WS patients and 4 sex matched controls were transformed into iPSCs, which were then differentiated to Neuroepithelial Stem Cells (NESCs), and further differentiated into neurons. RNA sequencing was performed at the NESC stage and after 4 and 8 weeks of neural development for 3 replicates per individual using the Illumina TruSeq stranded library polyA method on the NovaSeq6000 platform at NGI Stockholm. The data was preprocessed using the nf-core/rnaseq (https://nf-co.re/rnaseq) that includes quality control, data cleaning, and read alignment to GRCh38 (STAR, v2.6.1d)

  Dataset EGAD50000001728

• scRNAseq of ALS patients

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

  Dataset EGAD00001009623

• National Cancer Institute (NCI) Head and Neck Cancer Study

  Head and neck cancers have well-documented associations with tobacco and alcohol exposure, but the disease develops in only a small fraction of users, which implies an important role for genetic susceptibility. Therefore, head and neck cancers are an excellent model for studying genetic susceptibility to environmental carcinogens. The primary goal of this study is to perform a comprehensive two-stage, high-density, genome-wide single-nucleotide polymorphism (SNP) analysis of head and neck cancer cases and corresponding frequency matched controls to identify novel genetic risk factors for head and neck cancer. In the study, we genotyped 2242 head and neck cancer cases and 1198 controls using Illumina HumanOmniExpress-12v1 BeadChip.

  Study phs001173

• Genomics of Relapsed Small Cell Lung Cancer Progression

  Small cell lung cancer (SCLC) accounts for nearly 15% of all patients with lung cancer. Though the response to initial therapy is favorable in many patients, a majority of patients go on to develop recurrent disease which is very difficult to treat. The response rates to chemotherapy are very low and most patients succumb to relapsed SCLC within a few months. Virtually no progress has been made in the treatment of SCLC in the last three decades. In order to better understand the molecular alterations in relapsed SCLC, we have generated exome and RNA sequence from normal, primary tumor and relapse tissues of SCLC patients.

  Study phs001049

• Evaluation of size selection on cancer specific sequencing libraries

  A couple of previously characterized and sequenced libraries will be repeated using a couple of differing size selection criteria and skim sequenced using an Illumina HiSeq. The resulting sequence will be analyzed to determine the optimal DNA library size for our specific downstream analysis.

  Dataset EGAD00001000301

• WES data from primary CRC

  Whole exome sequencing from ffpe samples DNA was extracted from FFPE tissue samples from colorectal cancer biopsies. Exome libraries where prepared using the KAPA Hyper Plus Kit (Roche Diagnostics) followed by target enrichment by hybridisation capture using the Roche Hyper Exome Kit. Sequenced on NovaSeq6000 to generated 2x 151 paired-end reads.

  Dataset EGAD50000000924

• Dataset for early breast cancer samples

  This dataset contains WGS data for 27 tumor, control and patient derived culture samples of patients with breast cancer. Sequencing was performed on Illumina NovaSeq 6000 and HiSeq X using TruSeq Nano DNA Kit. The sequencing was always paired

  Dataset EGAD50000000860

• CLL targeted exome sequencing (2018-03-14)

  Aim to characterise cancer gene landscape in CLL, particularly in cases with mutated POT1 gene. Treatment-naive CLL cases will be interrogated by targeted exome sequencing using a cancer gene panel. . This dataset contains all the data available for this study on 2018-03-14.

  Dataset EGAD00001004037

• Asthma in the Lives of Families Today (ALOFT)

  Social interactions and the overall psychosocial environment have a demonstrated impact on health, particularly for people living in disadvantaged urban areas. Here we investigated the effect of psychosocial experiences on gene expression in peripheral blood immune cells of 251 children with asthma in Metro Detroit. Participants were included from an ongoing longitudinal study Asthma in the Lives of Families Today (ALOFT; recruited from November 2010-July 2018. The ALOFT project was established to identify the behavioral and biological pathways through which family social environments impact youth with asthma.In version 1 we used RNA-sequencing and a new machine learning approach to identify transcriptional signatures of 19 variables including psychosocial factors, blood cell composition and asthma symptoms. Using longitudinal data collected from a subset of the participants we showed that transcriptional signatures track the longitudinal changes in measured phenotypes. Importantly, we found 169 genes associated with asthma that are regulated by psychosocial factors, and 344 significant gene-environment interactions for gene expression levels. These results demonstrate that immune gene expression mediates the link between negative psychosocial experiences and asthma risk.In version 2, we focused on pubertal development. We identified substantial gene expression changes associated with age and pubertal development. We showed that genetic effects on gene expression change dynamically during pubertal development. Gene expression changes during puberty are correlated with gene expression changes associated with asthma and may explain sex differences in prevalence. Our results show that molecular data used to study the genetics of early onset diseases should consider pubertal development as an important factor that modifies the transcriptome.Version 3 uses single cell RNA-seq to study the dynamics of the transcriptional response to glucocorticoids in activated Peripheral Blood Mononuclear Cells from 96 African American children. We employed novel statistical approaches to calculate a mean-independent measure of gene expression variability and a measure of transcriptional response pseudotime. Using these approaches, we demonstrated that glucocorticoids reverse the effects of immune stimulation on both gene expression mean and variability. Our novel measure of gene expression response dynamics, based on the diagonal linear discriminant analysis, separated individual cells by response status on the basis of their transcriptional profiles and allowed us to identify different dynamic patterns of gene expression along the response pseudotime. We identified genetic variants regulating gene expression mean and variability, including treatment-specific effects, and demonstrated widespread genetic regulation of the transcriptional dynamics of the gene expression response.Version 4 adds scATAC-seq in activated peripheral blood mononuclear cells (PBMC) from 16 children with asthma with phytohemagglutinin (PHA) or lipopolysaccharide (LPS), and treated with dexamethasone (DEX), an anti-inflammatory glucocorticoid. We analyzed changes in chromatin accessibility, measured transcription factor motif activity, and identified treatment and cell-type specific transcription factors that drive changes in both gene expression mean and variability. We observed strong positive linear dependence between motif response and their target gene expression changes, but negative in variability changes. This result suggests that an increase of transcription factor binding tightens the variability of gene expression around the mean. We then annotated genetic variants in chromatin accessibility peaks and response motifs followed by computational fine-mapping of eQTL signals from a pediatric asthma cohort. We found that eQTLs were 5-fold enriched in peaks with response motifs and refined the credible set for 410 asthma risk genes, with 191 having the causal variant in response motifs. These results enhance the understanding of molecular mechanisms for asthma risk variants mediated by gene expression.

  Study phs002182

• Genome-wide Association Study and Meta-Analysis of Ewing Sarcoma

  We combined a set of 122 French Ewing sarcoma (EWS) cases from the Institut Curie, 19 EWS cases from the National Cancer Institute (NCI) Center for Cancer Research (CCR), and 29 EWS cases from the NCI Bone Disease and Injury Study. All EWS cases were confirmed by medical record review and the presence of a specific EWSR1-ETS translocation were noted when data was available. Each participant provided informed consent and each participating study was approved by the Institutional Review Boards of their study center. DNA was extracted using standard methods from blood, saliva (Oragene), or buccal cells. All de novo genotyping of EWS cases was performed at the NCI CGR on the Illumina OmniExpress-24 v1.1 array. Genotyping was performed according to manufacturer's guidelines using the Infinium HD Assay automated protocol.

  Study phs001549

• DAC for Rare Disease Studies from the Broad Institute

  Dac EGAC00001000566

• RNAseq data of polyA+ RNA from Leukocytes from 624 individuals of the ProgeNIA cohort.

  We sequenced the polyA+ fraction of the RNA of the leukocytes from 624 sardinian individuals with RNAseq. Prior to library preparation we added either ERCC ExFold RNA Spike-In. An average of 60M reads per samples with 51 bp paired-end reads were generated on a HiSeq 2000 (Illumina). Sequencing reads were then aligned using STAR-2.2.0c2 to the h37d5 reference genome supplemented with the ERCC spike-ins sequences. We further provided an exon-exon junction database that we generated from the GENCODE v14 annotation. In order to remove a contamination from a parallel experiment, we discarded any reads that mapped to the genomic regions of CBLB (chr3:105370773-105592330) and BCL11A (chr2:60672555-60784156). Filtered aligned reads (bam format) are shared.

  Dataset EGAD00001003102

• EGA synthetic data

  Synthetic Data One of the limitations in genomics research is that human genomics data is not openly available; access must be controlled according to participant consent agreements and data protection regulations such as GDPR. Obtaining authorization to access such data can sometimes take a long time, resulting in delays to important research work. In this context, synthetic genomic and phenotype data can be useful resources for researchers to avoid these delays. Synthetic data are artificially generated datasets, often created with algorithms, which can be used without the need for authorization to test new products and tools, build technical demonstrators, validate data models, and train AI models. The EGA provides access to synthetic cohort datasets augmented with rich synthetic metadata that overcomes these real data usage restrictions. Whilst synthetic datasets are not included in the general EGA mandate and services, we can consider such submissions and evaluate their acceptance on the basis of their unique use cases not already covered by existing synthetic datasets. Access to synthetic data studies is managed by the EGA Helpdesk Data Access Committee. Study ID Title Located in EGAS00001002472 CINECA synthetic cohort EUROPE UK1 referencing fake samples Central EGA EGAS00001005591 Synthetic data - Genome in a Bottle Central EGA EGAS00001005042 Test Study for EGA using data from 1000 Genomes Project - Phase 3 Central EGA EGAS00001005702 Human genomic and phenotypic synthetic data for the study of rare diseases Central EGA EGAS50000000190 EOSC4Cancer Synthetic Colorectal Cancer Genomic data Central EGA EGAS50000000086 Synthetic - FEGA Sweden Heilsa synthetic dataset December 2023 Federated EGA Sweden EGAS50000000678 Synthetic - GDI synthetic data Federated EGA Spain

  Documentation synthetic-data

• Analysis of DNA methylation in normal B cells and chronic lymphocytic leukemia

  Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes.As second study using these samples focued on evolution and resulting intra-tumor heterogeneity in CLL. We used 450k bead-chip arrays to study DNA methylomes in 68 chronic lymphocytic leukemia (CLL) cases, including 28 serial cases. The result establishs linked evolution of epigenetic and genetic alterations in progressive disease, revealing an important aspect of the biology of epigenetics in cancer.

  Study EGAS00001000534

• Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer

  The dataset for the study Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer includes 207 bam files from hybrid capture targeted error-correction next-generation sequencing (TEC-Seq) from plasma cell-free DNA and matched white blood cell DNA from 30 individuals with non-small cell lung cancer, alongside 46 bam files from whole exome sequencing of tumor and matched normal DNA for 21 individuals with non-small cell lung cancer who received immunotherapy-containing regimens.

  Dataset EGAD00001011991

• Inferring causal genes at type 2 diabetes GWAS loci through chromosome interactions in islet cells

  Resolving causal genes for type 2 diabetes at loci implicated by genome-wide association studies (GWAS) requires integrating functional genomic data from relevant cell types. Chromatin features in endocrine cells of the pancreatic islet are particularly informative and recent studies leveraging chromosome conformation capture (3C) with Hi-C based methods have elucidated regulatory mechanisms in human islets. However, these genome-wide approaches are less sensitive and afford lower resolution than methods that target specific loci. Methods: To gauge the extent to which targeted 3C further resolves chromatin-mediated regulatory mechanisms at GWAS loci, we generated interaction profiles at 23 loci using next-generation (NG) capture-C in a human beta cell model (EndoC-βH1) and contrasted these maps with Hi-C maps in EndoC-βH1 cells and human islets and a promoter capture Hi-C map in human islets. Results: We found improvements in assay sensitivity of up to 33-fold and resolved ~3.6X more chromatin interactions. At a subset of 18 loci with 25 co-localised GWAS and eQTL signals, NG Capture-C interactions implicated effector transcripts at five additional genetic signals relative to promoter capture Hi-C through physical contact with gene promoters. Conclusions: High resolution chromatin interaction profiles at selectively targeted loci can complement genome- and promoter-wide maps.

  Dataset EGAD50000000517

• Tumor-resident T-cell regulate responses to checkpoint blockade immunotherapies

  In cancer models, CD103+CD8 TRM cells are implicated in the response to anti-PD-1 immunotherapy, and a subset of CD4 TRM cells expressing the integrin CD49a is required for response to anti-CTLA-4 immunotherapy. We performed single-cell RNA sequencing on tumour-infiltrating T lymphocytes (TILs) isolated from colon carcinoma et unsupervised analyses reveal several TRM populations.

  Study EGAS50000000826

• Exome and RNA sequencing of pancreatic cancer biopsies and PDX models

  Pancreatic cancer biopsies and matching normal controls from 10 patients were exome sequenced. The same biopsies and PDX models derived from these were also subject to RNA sequencing.

  Dataset EGAD00001008113

• Understanding the development of resident memory T cells (Trm) in the human small intestine using integrative multiomic approaches: Paediatric RNA (2026-01-15)

  This study involves atlasing the development of the postnatal gut nervous system in order to elucidate the pathogenic mechanisms of Hirschsprung disease. . This dataset contains all the data available for this study on 2026-01-15.

  Dataset EGAD00001015797

• Integrative analysis of whole genome sequencing, RNA sequencing and methylome array of 20 carcinosarcomas.

  Carcinosarcomas of the female genital tract, or GCS, are uncommon but clinically highly aggressive neoplasms with biphasic histology of carcinomatous (C) and sarcomatous (S) elements. These tumors represent a unique model to study the genetic and phenotypic diversity of cancer cells and the link between cellular plasticity and resistance to therapy. The aim of ICGC GCS program is to genomically characterize C and S components of 20 tumors, from endometrium or ovary, through an integrative analysis of whole genome sequencing, RNA sequencing and methylome array.

  Study EGAS00001002271

• Somatic Mutations in Individual Skin Cells

  Ultraviolet (UV) radiation is the primary cause of melanoma through the acquisition of driver mutations in melanocytes. It also plays a significant role in oncogenesis in other skin cells, such as keratinocytes. However, the mutational profiles vary widely among different skin cancers, and the early mutational processes in different cell types from the same skin, is not well understood. Additionally, our preliminary studies also suggest that the mutation burden in different skin cells vary significantly based on risk factors such as the anatomical site and the use of tanning beds. To explore this, we employed innovative Next Generation Sequencing (NGS) tools to perform a site-matched comparison of the genomic landscapes of melanocytes, keratinocytes, and fibroblasts. From 20 biopsies of physiologically normal skin, collected from various anatomical sites across 16 donors, we have performed DNA-sequencing on 106 melanocytes, 78 keratinocytes and 13 fibroblasts. Of these samples, we have also simultaneously performed RNA-sequencing on 78 melanocytes, 46 keratinocytes and 9 fibroblasts. For normal bulk DNA, we also performed targeted (UCSF500; n=9) or exome sequencing (n=8) of skin or saliva samples from the donors.

  Study phs003683

• The impact of BNT162b2 mRNA vaccine against SARS-CoV-2 on adaptive and innate immune responses

  The mRNA-based BNT162b2 protects against severe disease and mortality caused by SARS-CoV-2 through induction of specific antibody and T-cell responses. Much less is known about its broad effects on immune responses against other pathogens. In the present study, we investigated the specific adaptive immune responses induced by BNT162b2 vaccination against various SARS-CoV-2 variants, as well as its effects on the responsiveness of human immune cells upon stimulation with heterologous viral, bacterial, and fungal pathogens. BNT162b2 vaccination induced effective humoral and cellular immunity against SARS-CoV-2 that started to wane after six months. We also observed long-term transcriptional changes in immune cells after vaccination, as assessed by RNA sequencing. Additionally, vaccination with BNT162b2 modulated innate immune responses as measured by the production of inflammatory cytokines when stimulated with various microbial stimuli other than SARS-CoV-2, including higher IL-1/IL-6 release and decreased production of IFN-α. Altogether, these data expand our knowledge regarding the overall immunological effects of this new class of vaccines and underline the need of additional studies to elucidate their effects on both innate and adaptive immune responses.

  Study EGAS00001006818

• Duplex sequencing of selected breast cancer patients

  Investigation of post-zygotic and germline variants using whole exome and ultra-deep duplex sequencing in paired uninvolved margin and primaty tumor samples from 126 breast cancer patients with differing survival outcomes, with skin or blood samples as reference. Pairs of uninvolved margin and blood samples were also collected for 15 reduction mammoplasty patients without personal or familial history of cancer, serving as controls.

  Dataset EGAD50000000769