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• Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

  Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.

  Study EGAS00001000942

• Whole_exome_sequencing_of_rare_autoimmune_related_phenotypes

  We aim to whole-exome sequence DNA samples from 75 individuals with severe forms of Inflammatory Bowel Disease and related autoimmune diseases to identify the rare, highly penetrant, variants that we believe underlie these phenotypes. Case samples will be obtained from both new and existing (UK IBD Genetics Consortium) collaborators to ensure only the most extreme cases are sequenced.

  Study EGAS00001000228

• Collection of Genotypic and Ethnographic Information from Individuals of South African Ethnic Groups

  The hunter-gatherers and pastoralists of South Africa retain the highest genetic diversity of any population. Genetic determinants of light skin pigmentation, reduced stature etc and other basic biomedical phenotypes are unique to samples with Southern African hunter-gatherer and pastoralist ancestry or retain ancestral haplotypes not found in other populations.

  Study EGAS00001004472

• Aligned reads from specific genomic locations derived from Illumina HiSeqX and HiSeq2000 whole genome sequence data

  This dataset includes bam files from 3,001 samples. These bam files include all read pairs where at least one of the reads aligns within 1kb of the C9orf72 repeat expansion. Additionally, these bam files also contain reads that are aligned to any of 29 pre-determined off target locations where the aligners are known to mis-align reads associated with this repeat expansion. These samples were sequenced using a combination of 2x100bp reads on an Illumina HiSeq2000 and 2x150bp reads on an Illumina HiSeqX sequencer and aligned using the Isaac aligner.

  Dataset EGAD00001003513

• Cell-free DNA TAPS for early cancer detection

  Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection. However, due to technological challenges associated with DNA methylation sequencing in low input cfDNA samples, most studies have been limited by DNA damage caused by bisulfite sequencing, or the qualitative nature of enrichment-based sequencing. Recently, we developed TET-assisted Pyridine Borane Sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and non-cancer controls. From just 10 ng cfDNA (1-3 mL of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.

  Study EGAS00001004962

• Single Cell and Spatial Transcriptomic Profiling of Haemophilus ducreyi Infection

  We investigated the immune response in end-point pustules formed by Haemophilus ducreyi in volunteers using an experimental infection model. Six volunteers were infected in the skin of the upper arm at three sites with 41-85 CFU of H. ducreyi loaded on an allergy testing device; a sham-inoculated (e.g., wound) site was also performed. Five volunteers (4 men and 1 woman; 2 Asians and 3 Whites; aged 27-46 years) formed pustules 6-8 days post infection; 1 volunteer spontaneously resolved all sites. If a volunteer formed pustules, biopsies were performed to collect their pustule and wound sites. Biopsy pairs for all 5 pustule formers were subjected to single cell (sc) RNA-seq. Sequencing libraries were prepared using the 10X Genomics Single-cell 3' RNA-seq kit. Spatial transcriptomics was performed on biopsy pairs from 4 of the 5 pustule formers. Ten micron sections were placed on 10X Genomics Visium slides for fresh-frozen tissue, and libraries were prepared with the 10X Genomics Visium spatial 3' gene expression kit. All samples were sequenced on an Illumina NovaSeq 6000. Count tables were produced with CellRanger and SpaceRanger, respectively, and Seurat was used to analyze the data. We identified 13 major cell types by scRNA-seq; the proportion of some immune cell subsets was increased in pustules compared to wound sites. We also localized the major cell types within the tissue by using the scRNA-seq data to deconvolve the spatial transcriptomic data. The FASTQ files and count tables from CellRanger and SpaceRanger are provided.

  Study phs003754

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

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

  Study JGAS000663

• Transcriptomic changes in amniotic fluid associated with the fetal inflammatory response

  The fetal inflammatory response (FIR) increases the risk of perinatal brain injury, particularly in extremely low gestational age newborns (ELGANs, < 28 weeks of gestation). Most FIR cases are subclinical, i.e., usually FIR does not trigger observable symptoms in the mother beyond those associated with premature birth. The study of transcriptomic changes asssociated with FIR in amniotic fluid could help finding new clinical actionable FIR biomarkers.

  Study EGAS50000000866

• Sequencing data for ICGC Oesophageal Adenocarcinoma tissue samples - 100

  Samples from the "100" project that are in the ICGC PanCancer project.

  Dataset EGAD00001001071

• RNA-seq, WGS and WES of Hepatocellular carcinomas, enriched in fibrolamellar carcinomas

  DNAJB1-PRKACA fusion is a specific driver event in fibrolamellar carcinoma (FLC), a rare subtype of hepatocellular carcinoma (HCC) occurring in adolescents and young adults. In older patients, molecular determinants of HCC with mixed histological features of HCC and FLC (mixed-FLC/HCC) remain to be discovered.This study aims to molecularly caracterize mixed fibrolamellar hepatocellular carcinoma (mixed FLC/HCC) within the molecular liver tumors diversity, in respect of pure FLC and different HCC subtypes. This study reunites WGS data (n=3, Tumoral/Non-Tumoral pairs), WES data (n=43, Tumoral/Non-Tumoral pairs) and RNAseq data (n=66, Tumoral only). On a trascriptomic level, most of the mixed-FLC/HCC RNAseq clustered in a robust subgroup of tumors all showing mutation or translocation inactivating BAP1 that codes for the BRCA1 associated protein-1.

  Study EGAS00001003837

• Fine Mapping of Eight Psoriasis Susceptibility Loci

  Psoriasis is a common immune-mediate disease identified through scaly patches of the skin. In this study we collected genotype information on 5,067 samples of European ancestry as a follow-up study of our initial GWAS (Nair et al. 2009). We designed an Illumina iSelect custom genotyping array with 2,269 tagging SNPs in the eight known psoriasis susceptibility regions (MHC, IL12B, IL23R, IL23A, TNFAIP3, IL13, RNF114, and TNIP1). The custom array also included 5,463 SNPs outside the eight known susceptibility regions, which were selected based on their association p-values in a meta-analysis of HapMap-imputed genotypes of two published GWAS-CASP (Nair et al. 2009) and (Ellinghaus et al. 2010). After quality control we analyzed 4,806 samples (2,699 cases and 2,107 controls). Please note: The accession number for this dbGaP study was incorrectly listed in the relevant publication (Das et al., 2015, Eur. J. Hum. Genet 23:844-853) as phs000019.v1.p1.

  Study phs001298

• RNA-seq from human embryonic tissues (additional samples 2018)

  How the genome activates or silences transcriptional programmes governs organ formation. Little is known about this in human post-implantation embryos undermining our ability to benchmark the fidelity of in vitro stem cell differentiation or cell programming, or interpret noncoding variation as potential causes of disease. Here, by studying histone modification we identified genome-wide open chromatin states and active repression across thirteen tissues during human organogenesis. We integrated the data with transcription to build the first view of how promoter states from nearly 20,000 genes differentially regulate alternative organ fates, arguing against bivalency during human organogenesis. The data illustrate tissue-specific as well as complex patterns of enhancer activity functional in zebrafish and impute master transcription factors. Overlaying 739 noncoding de novo mutations in patients allowed phenotypic correlation of developmental disorders to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for understanding normal and abnormal human development.

  Study EGAS00001003738

• HiChIP data and analysis in OCI-AML3

  Data and analysis of HiChIP assay of shZNF143 and shControl in OCI-AML3. CTCF was the ChIP antibody. Data files are paired-end reads in FASTQ format from the Illumina NovaSeq 6000 sequencer. Analysis files are paired-end bed files produced by FitHiChIP.

  Dataset EGAD50000001376

• Multiomics characterisation of the response to stimulation in Long Covid patients

  We generated 10X, droplet-based paired snRNAseq+snATACseq (Multiome) of the response to P. Aeruginosa or RPMI in patients suffering from Long Covid. In total, we included 15 patients. Single nuclei libraries are genetically multiplexed across donors, genotype files are available to enable demultiplexing. Phenotype sheets provide information of pools/donors as well as donor phenotype.

  Dataset EGAD50000000203

• RNA-Seq of GM adipose tissue samples

  This dataset contains 210 fastq files (RNA sequencing was performed in two centers) from 105 individuals (106 files in subcutaneous tissue and 104 files in visceral tissue). Of the 210 fastq files, 129 files are in PEx100 mode (appeared in a single fastq file) and 81 files are in PEx49bp mode (appeared in two separate fastq files). Sequencing was done on the Illumina HiSeq2000 platform.

  Dataset EGAD00001010253

• Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis

  Monozygotic (MZ) twins have been widely employed for dissection of the relative contributions of genetics and environment in disease. In multiple sclerosis (MS), an autoimmune demyelinating disease that commonly causes neurodegeneration and disability in young adults, disease discordance in MZ twins has been interpreted to indicate environmental importance in pathogenesis. However, genetic and epigenetic differences between MZ twins have been described, challenging the accepted experimental paradigm in disambiguating effects of nature and nurture. Here, we report the genome sequences of one MS-discordant MZ twin pair and messenger RNA (mRNA) transcriptome and epigenome sequences of CD4+ lymphocytes from three MS-discordant, MZ twin pairs. No reproducible differences were detected between co-twins among ~3.6 million single nucleotide polymorphisms (SNPs) or ~0.2 million insertion-deletion polymorphisms (indels). Nor were any reproducible differences observed between siblings of the three twin pairs in HLA haplotypes, confirmed MS-susceptibility SNPs, copy number variations, mRNA and genomic SNP and indel genotypes, or expression of ~19,000 genes in CD4+ T cells. Only two to 176 differences in methylation of ~2 million CpG sites were detected between siblings of the three twin pairs, in contrast to ~800 differences in methylation between T cells of unrelated individuals and several thousand differences between tissues or normal and cancerous tissues. In the first systematic effort to estimate sequence variation among MZ co-twins, we did not find evidence for genetic, epigenetic or transcriptome differences that explained disease discordance. These are the first female, twin and autoimmune disease genome sequences reported.

  Study phs000239

• Next Generation Sequencing in an IBD Pedigree Whole Genome Data

  In 2009 we identified a four-generation family with over 700 members and 41 affected with Crohn's disease (CD). At the time we sequenced the exome of 6 affected individuals but did not identify any coding variants which appear to explain the high prevalence of disease. Since then we have collected DNA from a large number of additional family members, genotyped linkage arrays on the entire family to refine genomic regions shared by identity by descent and genotyped affected and unaffected members at known CD risk loci identified by Genome Wide Association Studies (GWAS). These analyses have confirmed that a significant unexplained excess of disease remains after accounting for all known genetic factors, and that several regions of the genome are shared by a large fraction of affected individuals. We therefore perform whole genomes sequencing from 8 individuals which will allow us to impute the complete sequence of nearly all the members of the two largest and most severely affected branches of the family.

  Dataset EGAD00001000399

• A Phase I/II Trial of T Cell Receptor Gene Therapy Targeting HPV-16 E7 for HPV-Associated Cancers

  This is a phase I clinical trial testing the safety and efficacy of gene-engineered T cells expressing a T-cell receptor targeting an HLA-A*02:01-restricted epitope of HPV-16 E7 (E7 TCR T cells) in patients with metastatic HPV-16+ epithelial cancers. A total of 12 patients were treated. The maximum tested dose was tolerated. Side effects were most consistent with the expected toxicities of the lymphocyte-depleting conditioning regimen and high-dose aldesleukin. Six of the 12 patients demonstrated objective clinical responses. Translational studies of the infused T cell characteristics did not correlate strongly with clinical response. Genomic defects in the targeted peptide-HLA complex did demonstrate definitive mechanisms of resistance in some patients.

  Study phs002286

• Repotrectinib in NTRK fusion–positive advanced solid tumors: a phase 1/2 trial

  Early-generation TRK tyrosine kinase inhibitors (TKIs) approved for treating NTRK fusion–positive (NTRK+) solid tumors provide clinical benefit; however, resistance emerges. Repotrectinib is a next-generation ROS1/TRK TKI with a compact macrocyclic structure designed to improve durability of response. TRIDENT-1 is a registrational phase 1/2 trial assessing repotrectinib, a next-generation ROS1/TRK TKI, in adults with advanced solid tumors, including NTRK+ disease. The primary endpoint was confirmed objective response; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival and safety. Median follow-up ranged between 21.3 months and 25.7 months. In the TKI-naive cohort (n = 51; 95% confidence interval (CI)), the response rate was 59% (44–72); the median DOR was not estimable (NE); and the median PFS was 30.3 months (9.0–NE). In the TKI-pretreated cohort (n = 69; 95% CI), the response rate was 48% (36–60); the median DOR was 9.8 months (7.4–13.0); and the median PFS was 7.4 months (3.9–9.7). Of 30 TKI-pretreated patients with NTRK solvent front mutations, 16 had a response (53%; 95% CI: 34–72). Intracranial responses were observed in two of three TKI-naive patients and in four of six TKI-pretreated patients with measurable intracranial disease at baseline. Among all treated patients (n = 565), the most common any-grade treatment-related adverse event (TRAE) was dizziness (57%); most TRAEs were low grade; and 4% discontinued repotrectinib due to a TRAE. Overall, repotrectinib demonstrated durable systemic and intracranial responses with generally low-grade adverse events in patients with NTRK+ solid tumors, including those with previous TRK TKI treatment and solvent front mutations. These results support the use repotrectinib to treat patients with NTRK+ solid tumors. ClinicalTrials.gov identifier: NCT03093116 .

  Study EGAS50000001572

• Genomic landscape of poorly differentiated thyroid carcinoma

  Poorly differentiated thyroid carcinoma (PDTC) is a rare and aggressive subtype of thyroid cancer with limited molecular characterization. This study aims to define the somatic mutational landscape of PDTC using whole-genome sequencing. Paired tumour and matched normal blood samples were collected from six patients undergoing surgery. The overarching goal is to identify recurrent mutations, structural variants, and other genomic alterations associated with tumour aggressiveness and poor clinical outcomes.

  Study EGAS50000001134

• MOSAIC - Multi-Omics Spatial Atlas In Cancer

  MOSAIC is a collaborative initiative founded by Owkin, Lausanne University Hospital (CHUV), Charité Universitätsmedizin Berlin, University Hospital Erlangen (UKER), Gustave Roussy Institute in Paris, and University of Pittsburgh. The goal of MOSAIC is to build the largest collection of spatial omics data in cancer. By integrating comprehensive high quality clinical annotations with advanced deep profiling techniques, MOSAIC aims to uncover novel cancer subtypes and identify key drug targets and biomarkers within them.

  Study EGAS50000000689

• Phylogenetic reconstruction of adult blood cancer reveals early origins and lifelong evolution - TGS

  Mutations in cancer-associated genes drive tumour outgrowth. However, the timing of driver mutations and dynamics of clonal expansion that lead to human cancers are largely unknown. We used 580,133 somatic mutations from whole-genome sequencing of 1013 clonal haematopoietic colonies to reconstruct the phylogeny of haematopoiesis, from embryogenesis to clinical disease, in 12 patients with myeloproliferative neoplasms which are blood cancers more common in older age. JAK2V617F, the pathognomonic mutation driving the majority of these cancers, was acquired in utero or childhood, with upper estimates of age of acquisition from 33 weeks gestation to 10.8 years, in all 5 patients in whom JAK2V617F was either the only or the first driver event.  Driver mutations associated with age-related clonal haematopoiesis occurred prior to or following JAK2V617F,  as independent clonal expansions in JAK2V617F-mutated patients, and as large clonal expansions in JAK2V617F-unmutated patients . These mutations were also acquired in utero or childhood, with DNMT3A mutations occurring by 8 weeks of gestation to 7.6 years across 4 patients, and PPM1D mutation occurring by age 5.8yrs in a patient with MPN lacking phenotypic driver mutations. Sequential driver mutation acquisition was common, separated by decades across life, and often outcompeted ancestral clones. The mean latency between JAK2V617F acquisition and clinical presentation was 30 years (range 11-54 years). Rates of clonal expansion were inferred from phylogenetic trees and varied substantially (3% to 190% expansion/year), were affected by additional driver mutations, and were predictive of latency to clinical presentation. Driver mutations and rates of expansion would have been detectable in blood one to four decades before clinical presentation. This study reveals how driver mutation acquisition early in life with life-long growth and evolution underlie adult myeloproliferative neoplasms, providing opportunities for early detection and intervention and a new paradigm for cancer development.

  Dataset EGAD00001007715

• Phylogenetic reconstruction of adult blood cancer reveals early origins and lifelong evolution - WGS

  Mutations in cancer-associated genes drive tumour outgrowth. However, the timing of driver mutations and dynamics of clonal expansion that lead to human cancers are largely unknown. We used 580,133 somatic mutations from whole-genome sequencing of 1013 clonal haematopoietic colonies to reconstruct the phylogeny of haematopoiesis, from embryogenesis to clinical disease, in 12 patients with myeloproliferative neoplasms which are blood cancers more common in older age. JAK2V617F, the pathognomonic mutation driving the majority of these cancers, was acquired in utero or childhood, with upper estimates of age of acquisition from 33 weeks gestation to 10.8 years, in all 5 patients in whom JAK2V617F was either the only or the first driver event.  Driver mutations associated with age-related clonal haematopoiesis occurred prior to or following JAK2V617F,  as independent clonal expansions in JAK2V617F-mutated patients, and as large clonal expansions in JAK2V617F-unmutated patients . These mutations were also acquired in utero or childhood, with DNMT3A mutations occurring by 8 weeks of gestation to 7.6 years across 4 patients, and PPM1D mutation occurring by age 5.8yrs in a patient with MPN lacking phenotypic driver mutations. Sequential driver mutation acquisition was common, separated by decades across life, and often outcompeted ancestral clones. The mean latency between JAK2V617F acquisition and clinical presentation was 30 years (range 11-54 years). Rates of clonal expansion were inferred from phylogenetic trees and varied substantially (3% to 190% expansion/year), were affected by additional driver mutations, and were predictive of latency to clinical presentation. Driver mutations and rates of expansion would have been detectable in blood one to four decades before clinical presentation. This study reveals how driver mutation acquisition early in life with life-long growth and evolution underlie adult myeloproliferative neoplasms, providing opportunities for early detection and intervention and a new paradigm for cancer development.

  Dataset EGAD00001007714

• Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation Part 2

  This is 2nd part of data for original Control iPSC lines with clinically annotated genetic variants for versatile multi-lineage differentiation,

  Dataset EGAD00001005359

• T-cell receptor sequencing of tumor-infiltrating lymphocytes (TIL) in breast cancer

  The spatial distribution of tumor-infiltrating lymphocytes (TIL) predicts breast cancer outcome and response to systemic therapy, highlighting the importance of an intact tissue structure for characterizing patients’ tumors. Here, we present ST-FFPE, a spatial transcriptomics method for the analysis of formalin-fixed paraffin-embedded samples, which opens the possibility of interrogating widely available archival tissue. The method involves extraction, exome capture and sequencing of RNA from different tumor compartments microdissected by laser-capture, and can be used to study the cellular composition of various tumor environments. Focusing on triple-negative breast cancer (TNBC), we characterized T cells, B cells, dendritic cells, fibroblasts and endothelial cells in both stromal and intra-epithelial compartments. We found a highly variable spatial distribution of immune cell subsets among tumors. This analysis revealed that the immune repertoires of intra-epithelial T and B cells were consistently less diverse than those of stromal T and B cells. T-cell receptor (TCR) sequencing confirmed a reduced diversity and revealed higher clonality of intra-epithelial T cells relative to the corresponding stromal T cells. Analysis of the top ten dominant clonotypes in the two compartments showed a majority of shared but also some unique clonotypes both in stromal and intra-epithelial T cells. Hyperexpanded clonotypes were more abundant among intra-epithelial than stromal T cells. These findings validate the ST-FFPE method and suggest an accumulation of antigen-specific T cells within tumor core. Because ST-FFPE is readily applicable for analysis of previously collected tissue samples, it could be useful for rapid assessment of intratumoral cellular heterogeneity in multiple disease and treatment settings.

  Study EGAS00001007125

• Multiomic Sequencing of Paired Primary and Metastatic Small Bowel Carcinoids

  Small bowel carcinoids are insidious tumors that often have metastatic spread at the time of diagnosis. Limited studies on the mutational landscape of carcinoids indicate that the tumors have a relatively low mutational burden. Loss of chromosome 18q and loss of CDKN1B have been reported in a minority of tumors. The development of targeted therapies will depend upon the identification of mutations that drive the pathogenesis and metastasis of carcinoid tumors.

  Study EGAS00001006988

• Whole exome sequencing of uterine adenomyosis

  Uterine adenomyosis, defined by proliferation of the ectopic endometrial glands in myometrium, is a common benign uterine disorder that significantly impairs the quality of life of the women it affects. Adenomyosis lesions have chronic inflammatory reactions as well as cancer-like features such as invasive capacity into the normal myometrium. In contrast to endometriosis and leiomyoma, the genomic characterization of adenomyosis has yet to be reported. We conducted high-coverage whole exome sequencing analyses of freshly frozen adenomyosis samples, as well as co-occurring leiomyoma. Our WES analyses showed that adenomyosis is a clonal disorder with somatic mutations.

  Study JGAS000169

• Hereditary Gastric Cancer Syndromes: An Integrated Genomic and Clinicopathologic Study of the Predisposition to Gastric Cancer

  Gastric cancers are cancers of the stomach. Hereditary cancers are passed from parent to child. Researchers want to gather data about hereditary gastric cancers. Bulk RNA sequencing (RNA-seq) of signet ring cells (SRCs) and adjacent non-SRC epithelium (NEP) was performed on laser-capture microdissected (LCM) regions of interest found in risk-reducing total gastrectomy specimens from hereditary diffuse gastric cancer (HDGC) patients (Clinicaltrials.gov ID: NCT03030404). Twenty patients (6 male, 14 female) with confirmed HDGC were identified. Analysis of differentially expressed genes (DEGs) demonstrated upregulation of certain individual epithelial&#8211;mesenchymal transition (EMT) and proliferation genes. SRC regions had significant enrichment in pathways involved in T cell signaling. CIBERSORTx predicted significant increases in the presence of regulatory T cells (Tregs) specific to SRC regions.

  Study phs003422

• 47 urothelial cancer patients WES and 38 RNAseq

  We performed a global mutational landscape analysis using tumor samples from the 47 urothelial cancer patients included in MATCH-R or MOSCATO studies, with advanced metastatic disease and WES available (RNAseq is included for 38 patient samples).

  Dataset EGAD00001011063

• Benchmarking CRISPR Whole-genome Drop-out Screen - B&amp;S (2019-08-07)

  This study is a benchmarking exercise to explore potential source of variation between different CRISPR drop out libraries. . This dataset contains all the data available for this study on 2019-08-07.

  Dataset EGAD00001005233

• Engineering large chromosomal deletions by CRISPR-Cas9

  Arm-level chromosomal deletions are a prevalent and defining feature of cancer. A high degree of tumor-type and subtype specific recurrencies suggest a selective oncogenic advantage. However, due to their large size it has been difficult to pinpoint the oncogenic drivers that confer this advantage. Suitable functional genomics approaches to study the oncogenic driving capacity of arm-level deletions are limited. Here we present an effective technique to engineer arm-level deletions by CRISPR-Cas9 and create isogenic cell line models. We simultaneously induce double-strand breaks (DSBs) at two ends of a chromosomal arm and select the cells that have lost the intermittent region. Using this technique, we induced arm-level deletions on chromosome 11q (65 MB) and chromosome 6q (53 MB) in neuroblastoma cell lines. Such isogenic models enable further research on the role of arm-level deletions in tumor development and growth, and their possible therapeutic potential.

  Study EGAS00001005134

• Bulk RNA-seq of human muscle-invasive bladder cancer tissue samples before and after platinum-based chemotherapy (Chelushkin, van Dorp, et al., 2024)

  The current dataset represents bulk RNA-Seq gene expression profiling (with an exome library preparation kit) of muscle-invasive bladder cancer tissue samples obtained before and after platinum-based chemotherapy. 89 samples are pre-treatment transurethral resection of the bladder tumor (TUR-BT) tissue at diagnosis (baseline), 86 are post-treatment cystectomy tissue (resected tumor bulk), comprising 76 pairs of samples from the same patients. FASTQ files contain gene expression data.

  Dataset EGAD50000000446

• Fragmentomics analyses of urinary cell-free DNA permit multi-urologic cancer detection and reduction in tissue biopsies for prostate cancer

  This study demonstrated the close association between urinary cell-free DNA (cfDNA) methylation status and the fragmentation patterns in healthy controls and patients with various diseases. Fragmentomics-based methylation analysis (FRAGMA) enables accurate estimation of methylation levels in urinary cfDNA, which is proved by paired bisulfite sequencing and non-bisulfite sequencing data. FRAGMA showed high accuracy in deducing tissue-of-origin of urinary cfDNA in transplantation patients and pregnant women. Moreover, FRAGMA showed great potential in the detection and classification of multiple cancers from the urinary system, including bladder, kidney, and prostate cancer. This study demonstrated that FRAGMA could be applied to improve current diagnostic strategies based on urine samples.

  Study EGAS50000001431

• Sequence-Based Analysis of Human Breast Tumors

  The goal of this study is to study gene expression patterns in tumors, normal tissues, and cell lines.

  Study phs000676

• NPY methylated ctDNA is a promising biomarker for treatment response monitoring in metastatic colorectal cancer

  Study EGAS00001006820

• Rapid Acceleration of Diagnostics - Digital Health Technologies (RADx-DHT): NIH Digital Health Solutions for COVID-19: SAFER-COVID - Integration of Testing and Digital Health

  SAFER-COVID provides a set of self-management tools to consumers to track symptoms, test results, vaccine record, and environmental factors, such as exposure to others. Consumers may choose to integrate data from wearables and electronic health records (EHR) for self management. These data are used to enable multiple use cases such as return-to-work, activity risk assessment and self-management within SAFER-COVID.DOI: https://rapids.ll.mit.edu/10.57895/cmt5-gh78

  Study phs002540

• SG10K_Pilot - Large-scale whole-genome sequencing of three diverse Asian populations in Singapore

  Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions/deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore, and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ~24,800 years ago, and experienced significant admixture with East Asians ~1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, among which 14 harbored robust associations with complex traits and diseases. Finally, we showed that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions.

  Study EGAS00001003875

• Genetic and immune landscape evolution defines subtypes of MMR deficient colorectal cancer

  Mismatch repair deficient colorectal cancers have high mutation loads and many respond to immune checkpoint-inhibitors. We investigated how genetic and immune landscapes co-evolve in these tumors. All cases had high truncal mutation loads. Driver aberrations showed a clear hierarchy despite pervasive intratumor heterogeneity: Those in WNT/βCatenin, mitogen-activated protein kinase and TGFβ receptor family genes were almost always truncal. Immune evasion drivers were predominantly subclonal and showed parallel evolution. Pan-tumor evolution, subclonal evolution, and evolutionary stasis of genetic immune evasion drivers defined three MMRd CRC subtypes with distinct T-cell infiltrates. These immune evasion drivers have been implicated in checkpoint-inhibitor resistance. Clonality and subtype assessments are hence critical for predictive immunotherapy biomarker development. Cancer cell PD-L1 expression was conditional on loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD-L1 expression by cancer cells and likely contributes to the high recurrence risk of MMRd CRCs with impaired CDX2 expression.

  Study EGAS00001005769

• Population Architecture using Genomics and Epidemiology (PAGE): Causal Variants Across the Life Course (CALiCo): Coronary Artery Risk Development in Young Adults (CARDIA)

  CALiCo CARDIA The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a study examining how heart disease develops in adults. It began in 1986 with a group of 5115 black and white men and women aged 18-30 years. The participants were selected so that there would be approximately the same number of people in subgroups of race, gender, education (high school or less and more than high school) and age (18-24 and 25-30) in Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. These same participants were asked to participate in follow-up examinations during 1987-1988 (Year 2), 1990-1991 (Year 5), 1992-1993 (Year 7), 1995-1996 (Year 10), 2000-2001 (Year 15), and 2005-2006 (Year 20). A majority of the group has been examined at each of the follow-up examinations (90%, 86%, 81%, 79%, 74%, and 72%, respectively). While the specifics of each examination has differed somewhat, data have been collected on a variety of factors believed to be related to heart disease. These include conditions with clear links to heart disease such as blood pressure, cholesterol and other lipids. Data have also been collected on physical measurements such as weight and skinfold fat as well as lifestyle factors such as substance use (tobacco and alcohol), dietary and exercise patterns, behavioral and psychological variables, medical and family history, and other chemistries (e.g., insulin and glucose). In addition, subclinical atherosclerosis was measured via echocardiography during Years 5 and 10, computed tomography during Years 15 and 20, and carotid ultrasound during Year 20. A detailed description of the study and results from the first examination are summarized in Cutter et al (Controlled Clinical Trials, Volume 12, Number 1 [supplement], pages 1S-77S, 1991).

  Study phs000236

• Reasons for Geographic and Racial Differences in Stroke Cardiorenal GWAS

  REGARDS is a national, population-based, longitudinal study of incident stroke and associated risk factors including over 30,000 Black and White adults aged 45 years or older from all 48 contiguous U.S. states and the District of Columbia. The study was designed to investigate reasons underlying the higher rate of stroke mortality among Black participants compared to White participants and among residents of the Southeastern U.S. compared to other U.S. regions. By design, Black adults and residents of the deep south were oversampled. Between 2003 and 2007 (baseline visit) participants completed a computer-assisted telephone interview to collect demographic information and medication adherence, and an in-home visit for blood pressure measurements and collection of blood and urine samples. Following the baseline visit, participants have been contacted by phone at six-month intervals to obtain information on incident stroke or secondary outcomes. Additionally, samples and data were collected on about 50% of the original cohort during a second study visit an average of 10 years after the baseline visit. Genotyping was performed as part of an ancillary study on 10,788 (84% Black) participants using Illumina MEGA arrays.

  Study phs002719

• UCSF-CASCADE analysis of metastatic prostate cancer

  Targeted cancer therapy inevitably selects for tumor cells that harbor some form of therapy resistance. This phenomenon is a principle reason why advanced prostate cancer, which can be treated with agents targeting androgen signaling dependency and DNA repair failure, is a lethal condition. The influence of a patient's clinical history and disease evolution on how their disseminated tumors develop resistance has been difficulty to study, because few autopsy studies have been performed in heavily treated patients with DNA-repair deficient metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed how resistance to targeted cancer therapies evolved in an autopsy cohort of 54 mCRPC tumors from six men. This dataset includes targeted sequencing, exome sequencing, and RNA-seq conducted on these biopsies.

  Dataset EGAD00001010275

• An RCOR1 loss-associated gene expression signature identifies a prognostically significant DLBCL subgroup

  Effective treatment of diffuse large B cell lymphoma (DLBCL) is plagued by heterogeneous responses to standard therapy, and molecular mechanisms underlying unfavorable outcomes in lymphoma patients remain elusive. Here, we profiled 148 genomes with 91 matching transcriptomes in an R-CHOP-treated DLBCL cohort to uncover molecular subgroups linked to treatment failure. Systematic integration of high-resolution genotyping arrays and RNA-seq data revealed novel deletions in RCOR1 to be associated with unfavorable progression free survival (P = 0.001). Integration of expression data from the clinical samples with data from RCOR1 knockdowns in the lymphoma cell lines KM-H2 and Raji yielded an RCOR1 loss-associated gene signature comprising of 233 genes. This signature identified a subgroup of patients with unfavorable overall survival (OS) (P = 0.023). The prognostic significance of the 233-gene signature for OS was reproduced in an independent cohort comprising of 195 R- CHOP treated patients (P = 0.039). Additionally, we discovered that within the IPI low risk group, the gene signature provides additional prognostic value that was independent of the cell-of-origin phenotype. Taken together, we present a novel and reproducible molecular subgroup of DLBCL, impacting risk-stratification of R- CHOP treated DLBCL patients and revealing a new avenue for therapeutic intervention strategies.

  Study EGAS00001001000

• Pre_clinical_evolution_of_haematological_malignancies

  Deep targeted sequencing of 291 peripheral blood samples taken 1-20 years prior diagnosis of a haematological malignancy alongside age- and sex-matched controls. Key objective is to distinguish indolent age-related clonal haematopoiesis from pre-cancer and to derive predictive models for early risk-stratification.

  Study EGAS00001002964

• Somatic Copy Number Analysis of Endometrial Carcinomas

  Endometrial cancer (EC) is the most commonly diagnosed gynecologic malignancy in the United States and is the sixth leading cause of cancer death amongst American women. The purpose of this study was to identify somatic (tumor-specific) copy number alterations in 7 clear cell ECs, 31 serous ECs, 17 endometrioid ECs, and the clear cell components of 2 endometrioid/clear cell ECs. To this end, DNAs from de-identified primary endometrial tumors and matched non-tumor tissues or blood were hybridized to high-density Illumina Infinium HumanHap650Y Beadchips or to high-density Human660W-Quad Beadchips and the data analyzed to annotate somatic copy number alterations throughout the genome.

  Study phs001690

• Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

  The human placenta is a dynamic and cellular heterogeneous organ, which is critical in fetomaternal homeostasis and the development of preeclampsia. Previous work has shown that placenta-derived cell-free RNA increases during pregnancy. We applied large-scale microfluidic single-cell transcriptomic technology to comprehensively characterize cellular heterogeneity of the human placentas and identified multiple placental cell-type–specific gene signatures. Analysis of the cellular signature expression in maternal plasma enabled noninvasive delineation of the cellular dynamics of the placenta during pregnancy and the elucidation of extravillous trophoblastic dysfunction in early preeclampsia.

  Study EGAS00001002449

• Acquired Copy Number Alterations in Adult Acute Myeloid Leukemia Genomes

  We performed genome-wide copy number analysis with paired normal and tumor DNA obtained from 86 adult patients with de novo AML using the Affymetrix Genome-Wide Human SNP array 6.0 containing 1.85 million features. Acquired copy number alterations (CNA) were confirmed using an independent, higher resolution, custom array comparative genomic hybridization platform. A total of 201 somatic CNA were found in the 86 AML genomes (mean 2.34 CNA/genome), with FAB M6 and M7 AML genomes containing the most changes (10-29 CNA/genome). Twenty-four percent of AML patients with normal cytogenetics had CNA, while 40% of patients with an abnormal karyotype had additional CNA detected by SNP array, and several regions contained CNA in multiple AML genomes. The mRNA expression levels of 57 genes were significantly altered in 27 of 50 recurrent CNA regions &lt;5 megabases in size. Array data are available online at http://www.ncbi.nlm.nih.gov/geo/ as GEO accession #GSE10358. A total of 8 uniparental disomy (UPD) segments were identified in the 86 genomes and 6/8 UPD regions occurred in samples with a normal karyotype. Collectively, 40% of AML genomes contained alterations not found with cytogenetics, and 96% of these regions contained known or novel AML associated genes. 43/86 AML genomes had no CNA or UPD at this level of resolution. The number of CNA per genome was not associated with overall survival, independent of cytogenetic classification. In this study of 86 adult AML genomes, subcytogenetic CNAs or UPD did not add prognostic information to standard cytogenetics. However, arrays identified many somatically mutated oncogenes and tumor suppressor genes, and also genes not previously implicated in AML that may be relevant for pathogenesis. AML CNA segments from 86 adult AML patients are available through dbVar at ftp://ftp.ncbi.nlm.nih.gov/pub/dbVar/data/Homo_sapiens/nstd11_Walter_et_al_2009.

  Study phs000201

• SAPCS Blood RNA-seq of prostate cancer patients

  The study aims to quantify the gene expression in blood samples in 20 prostate cancer patients under the Southern African Prostate Cancer Study (SAPCS). The objective is to identify a list of differentially expressed genes.

  Study EGAS50000000702

• The Influence of Gut Microbiota on the Speciation and Toxicity of Mercury During Pregnancy

  There are few studies that have characterized maternal gut microbiota and fetal methylmercury exposure, yet microbes likely modulate this relationship. The primary objective of our pilot study was to determine associations between gut microbial taxa and mercury concentrations in multiple biomarkers (stool, hair, and cord blood). Our secondary objective was to determine the contribution of gut microbial mercury methylation to stool methylmercury.

  Study phs000970

• Case-control study with RNA-seq transcriptome between ASD patients and non ASD controls.

  Aim: To elucidate gene expression differences in the cerebellar tissues between ASD and normal control segmented by age. Object: The cerebellar tissues used in our study are from 16 autistic patients and 17 control patients. Method: We investigated the mRNA expression differences using RNA-seq between ASD and controls by age. We further investigated mRNA isoform expressions segmented by age.

  Study JGAS000668

• B Cell Receptor Study From Metastatic Breast Cancer Tumour Samples

  B and T cells are key components of the adaptive immune system and play an important role in anti-cancer immunity. In this study, we performed an integrative analysis of the B cell and T cell repertoires across 27 metastatic breast tumours obtained from 8 donors with therapy-resistant lethal metastatic breast cancer at the time of a warm autopsy.

  Study EGAS00001006976