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• HIV-phyloTSI: PANGEA (veSEQ-HIV)

  This dataset includes sample numbers TSI_0001 to TSI_0202 and TSI_0316 to TSI_0425 for the PANGEA (veSEQ-HIV) cohort of the study. Samples were sequenced using the Illumina NovaSeq system and the veSEQ-HIV method (see Bonsall, Golubchik et al 2020, DOI: 10.1128/JCM.00382-20). Each sample has a BAM file, and its associated reference file.

  Dataset EGAD50000001309

• CHIP panel sequencing of rheumatoid arthritis patients

  Targeted NGS sequencing data (bam and index files aligned to hg38) a total of 573 newly diagnosed, untreated RA patients and 163 healthy controls. The sequencing panel included 65 genes recurrently mutated in myeloid malignancies, to capture clonal hematopoiesis of indeterminate potential (CHIP) mutations. The median target coverage was 1700x across samples.

  Dataset EGAD50000001300

• Serum Proteome Profiling Identifies Early Markers of Therapeutic Response to Neoadjuvant Chemotherapy of Breast Cancer

  We performed a proteomic serum profiling of patients with non-metastasized breast cancer (BC) who received neoadjuvant chemotherapy (NACT). Samples were collected at three timepoints during NACT. Furthermore, we compared serum samples of BC patients pre-NACT to a control group of healthy volunteers.

  Dataset EGAD00010002330

• SNP_array

  33 ETMR samples were genotyped using Illumina HumanOmni2.5M array. Hybridization and scanning was done according to the manufacturer's instructions (Illumina). Copy number (Log R) and B allele frequency estimates were obtained sing the Genotyping module (v1.9.4) in GenomeStudio v2011.1 (Illumina). Normalized and log2-transformed copy number measurements were imported from genomestudio and analysed using R package CopyNumber to identify segments with similar copy number.

  Dataset EGAD00010001667

• Whole transcriptome sequencing of the dMMR colorectal cancer cohort

  We leveraged the ImmunoID NeXT platform, an Immune-enhanced multiomics platform to profile a cohort of patients with dMMR CRC. This sub-study includes the whole transriptome sequencing data

  Study EGAS50000001742

• Whole exome sequencing of the dMMR colorectal cancer cohort

  We leveraged the ImmunoID NeXT platform, an Immune-enhanced multiomics platform to profile a cohort of patients with dMMR CRC. This sub-study includes the whole exome sequencing data

  Study EGAS50000001744

• Resolution and methylation patterns of supernumerary marker chromosomes

  Herein we study the structure of ring and marker chromosomes in 10 carriers. The aim is to gain understanding of the formation and function of ring and marker chromosomes.

  Study EGAS50000001466

• GENOMIC INSTABILITY IN MISMATCH REPAIR DEFICIENT COLORECTAL CANCER

  Here we performed whole exome sequencing on a series of 47 mismatch repair (MMR) deficient colorectal cancers (CRC) in order to identified key events in tumoral initiation and progression

  Study EGAS00001002477

• Human T-bet governs innate and innate-like adaptive IFN-g immunity against mycobacteria.

  We report a patient with mycobacterial disease due to inherited deficiency of the transcription factor T-bet. PBMCs from the patient was analyzed with scRNA-seq.

  Study EGAS00001004504

• Whole exome and transcriptome sequencing of biliary tract cancer

  To uncover the full repertoire of genetic and transcriptomic landscape of biliary tract cancer (BTC), we molecularly characterized BTC based on genetic and transcriptomic alteration profiles.

  Study EGAS00001000950

• Testing_the_feasibility_of_genome_scale_sequencing_in_routinely_collected_FFPE_cancer_specimens_versus_matched_fresh_frozen_samples

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

  Study EGAS00001000173

• Control human putamen and Substantia Nigra

  The study is affiliated to the UKBEC sample of healthy human putamen and substantia nigra phenotype. The gender is from both male and female samples of the the phenotype.

  Study EGAS00001003065

• Poikiloderma_syndrome_RNAseq

  We will sequence the RNA of lymphoblast samples, transformed with EBV, which have poikiloderma syndrome with mutations in c16orf57. The aim of the experiment is to characterise RNA structural effects in this disease.

  Study EGAS00001000250

• Effect_of_FAM50_knockout_on_the_transcriptome

  A knockout clone has been generated for both FAM50A and FAM50B; knockout of the other gene is then performed and the transcriptome is analysed to look at the effect of dual gene loss.

  Study EGAS00001004836

• Clonal_human_oesophagus_punches

  We wish we perform whole genome sequencing on known clonal libraries of human oesophagus to provide a detailed investigation into differences in mutational burden, copy number and mutational signatures both within and between individuals.

  Study EGAS00001007696

• Targeted_NanoSeq_Buccal

  Targeted NanoSeq in buccal epithelium obtained longitudinally from a number of donors. A custom-designed panel of ~200 genes will be used to achieve high depth coverage (aiming for ~1000X at panel sites).

  Study EGAS00001005925

• Failure of Differentiation of the Rhombic Lip Constitutes Medulloblastoma

  We used single-cell transcriptomics to study cells from the developing human cerebellum, and show that different molecular subgroups of medulloblastoma resemble distinct glutamatergic progenitors.

  Study EGAS00001005826

• H3Africa - Trauma And Neurobiology: Maternal stress and transgenerational impact. Search for Epigenetic Markers

  This project aims to characterize the transgenerational genomic impact of genocide exposure and post-traumatic stress disorder (PTSD) in women survivors of the Rwandan genocide and their offspring.

  Study EGAS00001006645

• Spatial Transcriptomics of Pulmonary Vascular Remodelling in IPAH

  In compliance with the research ethics and governance under which these data and samples have been collected, the transcriptomic data are available through restricted access for approved researchers who agree to the conditions of use, i.e. keeping it secure and only using it for approved purposes. To apply for access please contact either a.lawrie@imperial.ac.uk, m.keles@imperial.ac.uk, b.wojciak-stothard@imperial.ac.uk.

  Dac EGAC50000001023

• Whole genome sequencing data to study therapeutic targeting of ependymoma

  This dataset contains whole genome sequencing data from 24 patients. For each patient a tumour and control sample has been sequenced on a Illumina HiSeq2000 instrument in paired-end mode. Up to three lanes per sample have been sequenced resulting in 112 Fastq files.

  Dataset EGAD00001003940

• Prostate Cancer Whole Genome Validations

  We propose to definitively characterise the somatic genetics of Prostate cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing. This study will aim to validate the findings of the whole genome study by re-sequencing regions of interest using a bespoke pulldown bait. See ICGC website for more information: http://icgc.org/icgc/cgp/70/508/71331

  Dataset EGAD00001000621

• SEQCAP_Internation_1q_Type_2_Consortium - Agilent SureSelec

  The aim of this project is to identify rare variants in the 1q region associated with type 2 diabetes. To this end 651 case samples and 651 control samples from six populations have been pooled (pool sizes range from 27-33 individuals), and are being sequenced. The hybridization solution being used captures the exons and UTRs of genes in the 1q region.

  Dataset EGAD00001000421

• Exome sequencing of serially transplanted genetically marked IC-enriched primary PDAC cultures.

  In order to elucidate whether newly acquired genetic alterations during serial transplantation of patient derived primary pancreatic cancer cultures contribute to the observed clonal dynamics in vivo, all coding genes of two patient derived primary cultures and derived genetically marked serial xenografts (1°/2°/3°) were sequenced.

  Dataset EGAD00001000884

• Single Cell Transcriptomic Analysis of Cellular Heterogeneity in Human Colorectal Tumours

  1,591 single cells from 11 colorectal cancer patients were profiled using Fluidigm based single cell RNA-seq protocol to characterized cellular heterogeneity of colorectal cancer. 630 single cells from 7 cell lines were profiled similarly to benchmark de novo cell type identification algorithms.

  Dataset EGAD00001002727

• Genomic profiling of patient-derived xenograft models of myxoid liposarcoma either sensitive or resistant to trabectedin

  The dataset consists of two patient-derived xenograft model of myxoid liposarcoma one sensitive and one resistant to trabectedin. Both models underwent the same treatment schedule with trabectedin (tree time points and one treatment with doxorubicin). We performed genomic profiling using Agilent OneSeq assay.

  Dataset EGAD00001005099

• Whole Exome Sequencing of 5 FFPE prostate samples (normal and tumour pairs) to identify mutations

  Whole Exome Sequencing was performed on radical prostatectomy formalin-fixed paraffin-embedded sample pairs (n = 6). Library prep was done by exon capture using the Illumina Truseq Exome kit and sequenced as 75bp paired end on Illumina NextSeq 500. Sequences were aligned to the human genome (hg38) using BWA.

  Dataset EGAD00001006107

• A method for multiplexed full-length single-molecule sequencing of the human mitochondrial genome

  Here we describe a method to target, multiplex and sequence full-length, native single-molecule the human mitochondrial genome utilizing the RNA-guided DNA endonuclease Cas9.

  Study EGAS00001006203

• To reveal the spectrum of gene mutations in grade II/III gliomas, whole exome sequencing of 52 samples including 4 multi-regional and 10 multi-time points sampling cases and 293 SNP-array were performed.

  To reveal the spectrum of gene mutations in grade II/III gliomas, whole exome sequencing of 52 samples including 4 multi-regional and 10 multi-time points sampling cases and 293 SNP-array were performed. Our analysis revealed high degrees of temporal/spatial heterogeneity generated during tumor expansion and relapse.

  Study EGAS00001001045

• We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.

  We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.

  Study EGAS00001002718

• Whole genome sequencing to detect spontaneous acquired mutations in mismatch repair-deficient human colon organoids

  Individual outgrowing organoids surviving the medium-based selection were manually picked and propagated as clonal lines for a couple of passages to avoid unexpected mutation accumulation before being harvested for WGS/WES. 1 µg of DNA was used for WGS/WES by Agilent SureSelect V7 kit, with 8Gb per sample (50X average mapped) data throughput, sequencing on NovaSeq 150PE

  Study EGAS50000000114

• RoCK and ROI single-cell transcriptome of one acute lymphoblastic leukemia patient

  Whole-transcriptome single-cell RNA sequencing (scRNA-seq) was performed following the manufacturer’s protocol (BD Rhapsody, BD Biosciences). Targeted enrichment of BCR::ABL1 transcripts was conducted using the RoCK and ROI-seq approach, based on the barcoded bead technology of the BD Rhapsody platform. In the RoCK and ROI-seq workflow, the template-switch oligonucleotides (TSOs) attached to BD Rhapsody beads were modified with one or multiple capture sequences specific to transcripts of interest, enabling targeted transcript capture during reverse transcription. ROI primers that are added during library preparation to direct amplification and sequencing toward these defined regions of interest (ROIs). Resulting libraries were sequenced on an Illumina sequencer.

  Dataset EGAD50000001976

• We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.

  We performed whole-exome sequencing and whole epigenome sequencing (RRBS) of samples collected from different time points during radiotherapy from thirty-four ESCC patients. We compared the genetic and epigenetic features of the different time biopsy samples to reveal the changes in ESCC received radiotherapy.

  Study EGAS00001002719

• Application of Hi-C sequencing to detect structural variants in B-cell acute lymphoblastic leukemia

  Large structural variants are easily detected by Hi-C sequencing as strong, distant signals on a Hi-C contact map. Translocations are frequently evident in B-ALL and accurate identification of these translocations can guide clinical treatment options. Here were apply shallow Hi-C sequencing as an unbiased, cost-effective approach to identify translocations among B-ALL patients.

  Study EGAS00001005605

• European Prospective Investigation into Cancer and Nutrition BAMs

  516 DNA samples were collected from individuals upon enrollment into the European Prospective Investigation into Cancer and Nutrition study between 1993 and 1998 across 17 different centers. 126bp pair-end reads sequencing data from the Illumina platform were converted to fastq format, the 2bp molecular barcode information at each read of the pair was trimmed and was written in the reads name. The Thymine nucleotide required for ligation was removed from the sequences. Burroughs-Wheeler Aligner (BWA-mem) was used for alignment of the processed fastq files to the reference hg19 genome, following indel-re-alignment using GATK. An in-house algorithm was written to collapse read families that share the same molecular barcode sequence

  Dataset EGAD00001003583

• Whole Genome sequencing of individuals from Val Borbera, Italy

  This study includes Phase 2 whole-genome sequencing data (at 4x depth)of 100 individuals from an Italian genetic isolate population (Val Borbera, abbreviated VBI) of the Italian Network of Genetic Isolates (INGI). The INGI-VBI_SEQ2 project aims to combine available extensive genetic and phenotypic data to the latest high-throughput genome sequencing technology and ad hoc statistical analysis to identify new rare genetic variants underlying complex traits.

  Dataset EGAD00001000731

• Understand Paratyphoid Disease - host responses to human challenge with S. Paratyphi A (2019-08-28)

  This project aims to evaluate the transcriptional response to disease measured in whole blood of participants who developed enteric fever after challenge and, importantly, those who were challenged but stayed well throughout the challenge period. This data will provide unique coverage of the transcriptome and will yield invaluable insight after integration with a wealth of clinical data collected during this trial. 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/ . This dataset contains all the data available for this study on 2019-08-28.

  Dataset EGAD00001005298

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

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

  Dataset EGAD00001005495

• ChIP-seq of primary AML patients with t(3;3)/inv(3)

  ChIP-seq was conducted in blasts from patients with t(3;3) AML to assess differences of the GATA2 super-enhancer between the translocated allele and the non-translocated allele. The dataset includes 2x H3K27ac ChIP-seq and 1x MYB ChIP-seq. ChIP samples were processed according to the Illumina TruSeq ChIP Sample Preparation Protocol (Illumina) or Diagenode Library V3 preparation protocol (Diagenode) and either sequenced single-end (1x 50 bp) on the HiSeq 2500 platform (Illumina) or paired-end (2x100 bp) on the Novaseq 6000 platform (Illumina). Briefly, reads were aligned to the human reference genome build hg19 with bowtie for single-end runs and bowtie2 for paired-end runs.

  Dataset EGAD00001006821

• HV31 - Read identifier list for local CCS, CLR, ONT and MGI reads

  This file contains read identifiers for local CCS, CLR, ONT and MGI reads for each of the eight selected genomic regions (HLA, KIR, IGH, IGK, IGL, TRA, TRD, andTRG). We extracted these reads by aligning whole-genome sequencing data to a draft whole-genome de novo assembly, and selecting reads that map to contigs representing each region. These reads were involved in the polishing and validation of the HV31 assembly. Please refer to the relevant manuscript (https://doi.org/10.1101/2021.02.03.429586) for additional details. Read identifiers are stored in JSON format. Along with the full FASTQ files, this file enables convenient re-analysis of the HV31 sequencing data in the eight selected regions.

  Dataset EGAD00001007761

• Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild type primary glioblastoma

  We stratified 69 primary IDH-wt GBM patients into TMZ-resistant (n = 29) and sensitive (n = 40) groups, using TMZ screening of the corresponding patient-derived glioma stem-like cells (GSCs). Genomic and transcriptomic features were then examined to identify TMZ-associated molecular alterations. Subsequently, we developed a machine learning (ML) model to predict TMZ response from combined signatures. Moreover, TMZ response in multisector samples (52 tumor sectors from 18 cases) was evaluated to validate findings and investigate the impact of intra-tumoral heterogeneity on TMZ efficacy.

  Dataset EGAD00001010156

• Genomic gain of EBV's LMP-1 in NKTCL

  The study found a high recurrence of genomic gain of LMP1 locus within EBV-associated NKTCL. The pilot data set and extended dataset of 77 WGS NKTCLs found 18/77 tumoral genomes to harbour genomic gain of LMP-1 locus within the EBV viral genomes within NKTCL tumoral sequencing data. The study also found 1/10 NKTCL cell lines to be positive for LMP-1 locus gain within EBV genomes too. This dataset includes solely the confirmatory WGS data of LMP-1 gain from NKYS cell lines using Oxford Nanopore long-read sequencing technology.

  Study EGAS50000000260

• Myocardial Infarction Genetics Exome Sequencing Consortium: Malmo Diet and Cancer Study

  The Malmo Diet and Cancer Study (MDCS) is a community-based prospective epidemiologic cohort of 28,449 subjects who were recruited for baseline examination between 1991 and 1996. From this cohort, 6103 subjects were randomly selected to participate in a cardiovascular cohort (MDCSCC), which seeks to investigate risk factors for cardiovascular disease. This study is a subset of those samples. All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Illumina's ICE Capture reagent and sequencing was performed on an Illumina HiSeq 2000 or 2500.

  Study phs001101

• Pooled Genome-Wide Analysis of Kidney Cancer Risk (KIDRISK)

  Incidence rates of renal cell carcinoma (RCC) are rising and the latest estimates show that it accounts for over 300,000 cases and 120,000 deaths worldwide each year. Mechanisms underlying RCC occurrence are not fully understood and a large part of the disease heritability remains unexplained. The study aimed at augmenting the size of available RCC genome-wide association studies to increase the statistical power to detect genetic variants associated with the disease. The study includes genome-wide genotyping data from RCC cases (n=2,781) and controls (n=2,526) recruited in Western Europe, Central and Eastern Europe, and Australia.

  Study phs001271

• Transcriptome Sequencing of Pediatric Neuroblastoma

  Neuroblastoma is the most common extra-cranial solid tumor in children. It represents 8% to 10% of all childhood cancers. Stage 4 Neuroblastoma is characterized by its clinical heterogeneous outcome. The special category, stage 4S tumors (2-5% of all NB) are chemo-sensitive, and the patients show spontaneous regression. On the other hand, MYCN amplification (25-30% of all NB) is associated with poor outcome of neuroblastoma, thus we further categorize stage 4 neuroblastoma into MYCN non-amplified and MYCN amplified group. Here we use transcriptome sequencing to characterize the transcriptome in 29 stage 4 Neuroblastoma samples.

  Study phs000868

• Whole Genome Sequencing of Skull-Based Chordoma

  Chordoma is a rare bone tumor, which is believed to originate from notochordal remnants. Based on the United States Surveillance Epidemiology and End Results (SEER) data, the incidence of chordoma varies by gender and race; however, little is known about the etiologic factors that predispose to it. Genomic profiling studies of chordoma are limited, particularly in the Chinese population. We therefore conducted a detailed molecular characterization of paired chordoma tumor/normal tissues using fresh frozen tissues and blood collected from skull-based Chinese chordoma patients. These analyses included whole exome sequencing and RNA sequencing analyses.

  Study phs002301

• High-Throughput RNA Isoform Sequencing using Programmable cDNA Concatenation

  MAS-ISO-seq is a novel technique for programmably concatenating cDNAs into single molecules for optimal long-read sequencing. In practice, this boosts throughput >15 fold to nearly 40 million cDNA reads per run on the PacBio Sequel IIe sequencer. We have validated this method via application to synthetic RNA isoforms and single-cell sequencing of tumor-infiltrating T cells. Results demonstrated a >30 fold boosted discovery of differentially spliced genes and robust cell clustering, as well as canonical PTPRC splicing patterns across T cell subpopulations and the concerted expression of the associated hnRNPLL splicing factor.

  Study phs003200

• Whole Exome Sequencing of Uveal Melanoma

  Uveal melanoma is a rare form of melanoma that occurs in the eye and has no effective treatment once metastatic. To further characterize the genomic events driving uveal melanoma, whole exome sequencing was performed on 61 primary tumors derived from enucleations, 3 liver metasases, and paired normal DNA. Recurrent somatic genetic alterations including point mutations, small insertions and deletions, as well as copy number variations were identified. In addition, RNA sequencing of uveal melanoma cell lines expressing shRNAs was performed from total RNA as well as polysome-associated mRNA in order to identify transcripts regulated by EIF1AX at the level of translation.

  Study phs001370

• Mosaic Chromosomal Aneuploidies Detection in Clinical Samples

  Mosaic chromosomal aneuploidy occurs when only a subset of cells carries an abnormal number of chromosomes. Mosaic aneuploidy has been reported in multiple types of diseases. Here we have developed a new sequencing-based approach to identify, characterize and quantify mosaic aneuploidy events in human tissue samples. This ongoing study has begun with results from sequencing data from two clinical patients, one with autism spectrum disorder (ASD) and the other with hemihyperplasia (OMIM 235000). We captured ~100,000 common SNPs from the samples to identify the nature of the mosaic aneuploidy events in each of the samples.

  Study phs001557

• OCD Collaborative Genetic Association Study (OCGAS)

  The OCD Collaborative Genetics Association Study Group (OCGAS) was funded by NIMH to conduct a genome-wide association study to identify disease susceptibility loci of early-onset obsessive-compulsive disorder (OCD). Collaborators at Johns Hopkins, Brown, Columbia, MGH, UCLA, and NIMH evaluated 2,000 individuals with OCD and collected DNA from these individuals and both their parents. The genotyping and analyses was performed in two stages. In the first stage 1,065 families (comprising 1406 patients with OCD and 2895 individuals in total) were genotyped on the Illumina OmniExpress GWA (SNPs) panel at the JHU SNP Center.

  Study phs000903

• Studies in the Pathogenesis of Systemic Capillary Leak Syndrome (SCLS, Clarkson Disease)

  Systemic capillary leak syndrome (Clarkson disease) is an ultra-rare disease of unknown etiology. Patients experienced transient and recurrent episodes of hypotensive shock and massive peripheral edema due to plasma extravasation, often precipitated by minor viral infections. Disease onset occurs most frequently in middle age, and there is no family history. More than 90% of patients with the disease have monoclonal gammopathy of unknown significance (MGUS). The goal of the study is to determine pathogenic mechanisms and identify genetic underpinnings of the disease. Toward this end, we performed whole genome sequencing (WGS).

  Study phs003261

• NSD2 E1099K Drives Relapse in Pediatric Acute Lymphoblastic Leukemia by Disrupting 3D Chromatin Organization

  NSD2 p.E1099K (EK) is a mutation shown to be enriched in patients that relapse with pediatric Acute Lymphoblastic Leukemia (ALL). This work aims to uncover 3D chromatin architecture-related mechanisms responsible for drug resistance or therapy failure in these patients. We investigated this by performing Hi-C, ATAC-Seq, and RNA-Seq on three B-ALL cell lines heterozygous for EK either expressing a NSD2 targeting small RNA (sRNA) or a non-targeting small hairpin RNAs (shRNA). We also performed RNA-Seq on three matched diagnosis/relapse B-ALL samples with the relapse enriched EK mutation.

  Study phs003195

• NHLBI TOPMed - NHGRI CCDG: The Vanderbilt AF Ablation Registry

  The Vanderbilt Atrial Fibrillation Ablation Registry (VAFAR) was founded in 2011. Patients with AF referred for AF ablation are prospectively enrolled. A detailed clinical history is recorded, along with imaging data (cardiac MRI or CT). Blood samples are obtained for DNA extraction at the time of ablation. Details of the ablation procedure are recorded. Patients are longitudinally followed to monitor for AF recurrence. VAFAR contributed 171 samples submitted to dbGaP for WGS: 115 were from male subjects, of which 113 were white/non-Hispanic and 2 were Hispanic; 56 were from females, of which all 56 were white/non-Hispanic.

  Study phs000997

• The UC San Diego Chronic Lymphocytic Leukemia (CLL) Study

  The UC San Diego Chronic Lymphocytic Leukemia Study is designed to identify genetic, epigenetic, and transcriptional changes important for CLL. This data release consists of samples collected to 1) identify genomic changes associated with CLL progression using serially collected tumor samples; 2) characterize the transcriptional consequences of SF3B1 mutation through RNA-seq; and 3) characterize the expression profiles of ROR1+ vs. ROR1- tumors. The samples were collected from participants at the University of California, San Diego Moores Cancer Center and the data was generated at UC San Diego or in collaboration with the BC Cancer Agency Genome Sciences Centre.

  Study phs000767

• Germline DNA Methylation Associated with Breast Cancer Predisposition

  Understanding and explaining hereditary predisposition to cancer has focused on the genetic etiology of the disease. However, mutations in known genes associated with breast cancer such as BRCA1 and BRCA2 account for less than 25% of familial cases of breast cancer. Heritable epigenetic modifications, in the form of hypermethylated MLH1 promoter alleles, have recently been shown to promote hereditary nonpolyposis colorectal cancer. We investigated the potential for an epigenetic basis for hereditary breast cancer by performing deep bisulfite sequencing of CpG islands and known promoter regions in germline DNA from 100 familial or early-onset breast or ovarian cancer patients.

  Study phs001699

• Multi-Omic Investigation of Beckwith-Wiedemann Syndrome Wilms Tumor

  Wilms’ Tumor (WT), also known as nephroblastoma, is one of the most common malignant kidney tumors diagnosed in children. One of the most common WT predisposition syndromes is Beckwith-Wiedemann Syndrome (BWS, OMIM: 130650), which affects approximately 1/10,000 live births. In this study, we perform Whole Exome Sequencing (WES), DNA methylation array, and messenger RNA-Sequencing (mRNA-Seq), to examine the genomic, methylomic, and transcriptomic signature of BWS WT. We analyzed six tumor-normal paired samples, three BWS tumor only samples, and four non-BWS control samples to identify BWS WT drivers.

  Study phs002769

• FinaleMe: Predicting DNA Methylation by the Fragmentation Patterns of Plasma Cell-Free DNA

  Analysis of DNA methylation in cell-free DNA (cfDNA) reveals clinically relevant biomarkers but requires specialized protocols and sufficient input material that limits its applicability. Millions of cfDNA samples have been profiled by genomic sequencing. To maximize the gene regulation information from existing datasets, we developed FinaleMe, a non-homogeneous Hidden Markov Model (HMM), to predict DNA methylation of cfDNA and, therefore, tissues of origin directly from plasma whole genome sequencing (WGS). We validated the performance with 80 pairs of deep and shallow coverage WGS and whole genome bisulfite sequencing (WGBS) data from both cancer patients and healthy controls.

  Study phs003287

• Whole Genome Sequencing of Bilateral Cleft Lip and Palate Families from Africa: CIDR

  The focus of this study is to identify and test both common and rare genetic variants that elevate risk for CL/P, and to identify genetic variants associated with specific orofacial cleft (OFC) phenotypes in the population that has accumulated the greatest genetic variation in the human race. We hypothesize that bilateral complete cleft lip and palate (BCLP), the most clinically severe form of OFC, is associated with a higher mutation load than less severe forms (cleft lip only and unilateral cleft lip and palate) and focusing on BCLP will facilitate the discovery of novel risk variants.

  Study phs002623

• High Sensitivity ctDNA Analysis Using a Novel Panel and NOIR-SS Technology for Monitoring Advanced Urothelial Carcinoma

  This dataset contains sequencing data generated by targeted amplicon analysis using the NOIR-SS method in 15 patients with advanced urothelial carcinoma. Formalin-fixed paraffin-embedded (FFPE) tumor tissues (15 samples) and plasma cfDNA (50 samples) were analyzed. Tumor tissues were subjected to targeted panel sequencing to identify mutations in TP53, FGFR3, TERT, and KRAS/HRAS. Plasma cfDNA was analyzed using a tumor-informed approach focusing on the mutations identified in matched tumor tissues. Sequencing was performed on the Ion PGM or Ion S5 XL platform. Raw sequencing data are provided in FASTQ format under controlled access.

  Study JGAS000836

• Research for candidate genes of splenic epidermoid cyst

  Splenic epidermoid cyst is a very rare benign tumor-like lesion filled with fluid or semi-fluid material. It occurs mostly in 2nd or 3rd decades of life with some female dominance. Most cases are asymptomatic and the clinical symptoms are dependent on the size of the cyst. Exome re-sequencing is an efficient strategy to selectively sequence the protein-coding regions of the genome, and has increasingly been used to identify novel genetic variants underlying Mendelian diseases. In this study, exome re-sequencing of 8 Japanese patients with splenic epidermoid cyst were conducted.

  Study JGAS000008

• Global Architecture of anti-Tumor B-Cell Immunity against Gastric Cancer

  Recent successes in tumor immunotherapies have warranted the importance of tumor immunity. Compared to the T-cell immunity, B-cell immune system in cancer is largely elusive. Here we immunogenetically profiled tumor-infiltrating B-cell and T-cell repertoires for exome- characterized diffuse-type gastric carcinoma (DGC), which is remarkable for its B-cell infiltrations, unraveling previously un-defined architectures of B-cell immunity and its interplays with T-cell immunity in cancer. We also performed transcriptome analysis to enumerate the proportions of tumor-infiltrating immune cells in the gastric cancer environment .

  Study JGAS000141

• CAGE analysis for endometrial carcinoma

  For endometrial cancer patients, lymphadenectomy is recommended to exclude rarely metastasized cancer cells. This procedure is performed even in patients with low risk of recurrence despite the risk of complications such as lymphedema. A method to accurately identify cases with no lymph node metastases (LN-) before lymphadenectomy is therefore highly required. We approached this clinical problem by examining primary lesions of endometrial cancers with CAGE (Cap Analysis Gene Expression), which quantifies promoter-level expression across the genome. Fourteen profiles delineated distinct transcriptional networks between LN?+?and LN- cases, within those classified as having the low or intermediate risk of recurrence.

  Study JGAS000124

• Global Architecture of anti-Tumor B-Cell Immunity against Gastric Cancer

  Recent successes in tumor immunotherapies have warranted the importance of tumor immunity. Compared to the T-cell immunity, B-cell immune system in cancer is largely elusive. Here we immunogenetically profiled tumor-infiltrating B-cell and T-cell repertoires for exome- characterized diffuse-type gastric carcinoma (DGC), which is remarkable for its B-cell infiltrations, unraveling previously un-defined architectures of B-cell immunity and its interplays with T-cell immunity in cancer. We also performed transcriptome analysis to enumerate the proportions of tumor-infiltrating immune cells in the gastric cancer environment .

  Study JGAS000103

• 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

• Single B cell analysis in pemphigus patients

  pemphigus is caused by autoantibodies that target cell-cell adhesion molecules, desmoglein(Dsg). Clinical effect of anti-CD20 antibody therapy suggtests that Dsg-specific memory B cell, the precursor of autoantigen secreting plasmablast, may play an important role of disease activity. This study aimed to isolate Dsg-specific memory B cell using recombinant labeled Dsg proteins and performed single cell RNA-sequence to detect autoimmune B cell specific gene expression. For control, we also isolate non-Dsg specific memory B cells from same patients, or forein antigen (Flu HA) specific memory B cells from vaccinated healthy volunteers.

  Study JGAS000281

• Japanese Reference Genome JG1

  The complete human genome sequence is used as a reference for next-generation sequencing analyses. However, some ethnic ancestries are under-represented in the reference genome (e.g., GRCh37) due to its bias toward European and African ancestries. Here, we perform de novo assembly of three Japanese male genomes using >100�� Pacific Biosciences long reads and Bionano Genomics optical maps per sample. We integrate the genomes using the major allele for consensus and anchor the scaffolds using genetic and radiation hybrid maps to reconstruct each chromosome. The resulting genome sequence, JG1, is contiguous, accurate, and carries the major allele for a Japanese population.

  Study JGAS000259

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

  To elucidate the regulation of B cell recptor repertoire in B cell subsets and its contribution to autoimmune diseases, B cell subsets from 36 Systemic Lupus Erythematosus(SLE), 90 Systemic Sclerosis(SSc), 85 Myositis(IIM), 21 Mixed Connective Tissue Disease(MCTD), 18 Sjogren's syndrome(SjS), 27 Rheumatoid Arthritis(RA), 23 Behcet's disease(BD), 18 Adult Onset Still���s Disease(AOSD), 24 ANCA-associated Vasculitis(AAV), 16 Takayasu���s Arteritis(TAK) and 137 healthy controls(HC) were collected (Naive_B, USM_B, SM_B, DN_B, Plasmablast. RNA-seq and BCR-mapping was performed with each B cell subset samples.

  Study JGAS000485

• Whole_Exome_Sequencing_for_Characterization_of_Disease_Causing_Mutations_in_two_Pakistani_Families_Suffering_from_Autosomal_Recessive_Ocular_Disorders_

  We propose to use whole exome Agilent solutionprobes and paired end Illumina sequencing to sequence 4 individualsfrom two families suffering from novel autosomal recessive disease[microphthalmia, MOP (OMIM %251600) and non-syndromic persistenthyperplastic primary vitreous, PHPV (OMIM %611311)]. Selectedcandidate variants will subsequently be genotyped in the remainingfamily members in Pakistan with the aim of identifying the rarehomozygous recessive mutations responsible for the disease phenotype. 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 EGAS00001000026

• Human four week embryo head as reference for generating an enhancer compendium for neuronal and neural crest development using neural tube organoids.

  This study has the aim of generating an enhancer code compendium of early human neuronal and neural crest development. For this purpose, we generated human neural tube organoids from single cells from two induced pluripotent stem cell lines. The organoids were subject to combined single cell multiomics at four time points of differentiation. To evaluate the biological relevance of the cell types and states obtained from the organoids, we compared with data obtained from 10XGenomics single cell multiomics on the head of a single four weeks post conception human embryo.

  Study EGAS50000001031

• Whole-Genome Shotgun Metagenomic Analysis of Rectal Mucus for Colorectal Cancer Detection

  This study evaluates the use of rectal mucus as a minimally invasive biospecimen for colorectal cancer (CRC) detection through whole-genome shotgun metagenomic sequencing. 408 rectal mucus samples were collected from patients suspected to have colorectal cancer and sequenced. These samples were analyzed to characterize microbial community composition and its association with CRC stage and anatomical site. These data provide insights into tumor-proximal microbiome signatures and demonstrate the potential of rectal mucus sampling for early and accurate CRC diagnosis. This is 1 of 4 sequencing experiments on the same sample type.

  Study EGAS50000001310

• Single cell transcriptomics of human kidney organoid endothelium reveals vessel growth processes and arterial maturation upon transplantation

  Human induced pluripotent stem cell-derived kidney organoids have potential for disease modeling and regenerative medicine purposes. However, they lack a functional vasculature in in vitro culture. Here, we transplanted kidney organoids at day 7+12 of differentiation in the coelomic cavity of chicken embryos. We then compared human endothelial cells from transplanted organoids to their respective untransplanted controls at d7+13 and d7+20 using scRNAseq. We demonstrate metabolic and phenotypic effect of transplantation with increased endothelial cell proliferation and differentiation to a fetal-like renal arterial/afferent arteriolar phenotype.

  Study EGAS50000001068

• Test Study for EGA using data from 1000 Genomes Project - Big CRAM, BAM, VCF and BCF files used for testing

  This is a test study for EGA using data from 1000 Genomes Project, specifically created to add more diversity to the existing dataset EGAD00001003338. This Test Study should NOT be confused with the real study of 1000 Genomes Project - Phase 3. Specifically, this study encompasses 4 CRAM, 4 BAM, 2 VCF and 2 BCF files, of different sizes (all above 1 GB), used for testing downloads and monitoring services. It also contains their respective indexes: crai for crams, bai for bams, tbi for vcfs and csi for bcfs.

  Study EGAS00001006718

• WGS of MPNSTs and ANNUBPs

  Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly aggressive soft-tissue sarcomas with a poor prognosis and a lack of therapeutic options. In this study, we analyse the whole genomes of 20 MPNSTs and 7 ANNUBPs to find recurrent genomic alterations that can help us better understand the biology of MPNSTs. Merging this data with another public dataset, we are able to identify three genomic MPNST subgroups with distinct biological and clinicopathological features that can inform management and precision treatments. Published in "Identification of Malignant Peripheral Nerve Sheath Tumor (MPNST) subtypes with distinct genomic identities."

  Study EGAS50000001734

• Discordant_Monozygotic_Twins_ALS(Transcriptomics)

  Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration. Despite known genetic contributions to both familial and sporadic ALS cases, much of ALS heritability remains unexplained, suggesting the involvement of other genetic and epigenetic factors. To address this gap, we used a comprehensive multi-omics approach, in a pair of Italian monozygotic twins discordant for ALS, integrating DNA methylation, transcriptomics, and whole exome sequencing (WES). Here we share transcriptomic data derived from bulk RNA-seq on RNA extracted from PBMCs of the twin pair. This analysis revealed distinct transcriptomic profiles underlying the discordant disease phenotypes.

  Study EGAS50000000909

• Bleomycin Induced Pneumonitis cohort of the Exceptional Responders Program of the Garvan Institute of Medical Research

  Bleomycin is a cytotoxic antibiotic and forms a key component of the curative-intent chemotherapy regimens for germ cell tumours (GCT) and lymphoma. However, the drug can be associated with a range of lung toxicity, including idiosyncratic inflammation termed bleomycin induced pneumonitis (BIP), which can lead to irreversible interstitial fibrosis and death. This study aims to identify germline genomic changes associated with BIP in patients receiving bleomycin as treatment for GCT or lymphoma, who develop clinically significant BIP despite low predicted risk based on absence of traditional risk factors.

  Study EGAS50000001545

• Transcriptomic profiling of skin biopsies from psoriasis patients following treatment with Zasocitinib

  The objective of this study is the exploratory analysis and characterization of psoriasis using RNA-seq-based profiling. Specifically, the cutaneous and serum biomarker profiles associated with the molecular, histological and clinical effects of Zasocitinib treatment in patients with moderate-to-severe plaque psoriasis were characterized. To evaluate differences between the transcriptomic profiles of Zasocitinib- and placebo-treated patients, exploratory biomarker endpoints included quantification of skin biomarkers, such as immune cell infiltration and mRNA expression levels in lesional and non-lesional skin, as well as quantification of circulating cytokines and other inflammatory biomarkers.

  Study EGAS50000001548

• The variable genomic landscape during osteosarcoma progression: insights from a longitudinal WGS analysis

  Osteosarcoma is a primary bone tumor that exhibits a complex genome characterized by gross chromosomal abnormalities. Osteosarcoma patients often develop metastatic disease, resulting in limited therapeutic options and poor survival rates. To gain knowledge on the mechanisms underlying osteosarcoma heterogeneity and metastatic process, it is important to obtain a detailed profile of the genomic alterations that accompany osteosarcoma progression. Therefore, in this study we performed WGS on multiple tissue samples from six patients with osteosarcoma, including the treatment naïve biopsy of the primary tumor, resection of the primary tumor after neoadjuvant chemotherapy, local recurrence and distant metastases.

  Study EGAS50000000329

• Disease recurrence after pathologic response (Recurrence DNAseq)

  In this study we aim to gain insight into the mechanisms of immune evasion after initial pathologic response to neoadjuvant immune checkpoint inhibition in macroscopic stage III melanoma by pooling data of the neoadjuvant OpACIN, OpACIN-neo and PRADO trials(EGAD00001012116, EGAS00001004832, EGAD00001006730, EGAS50000000268). Therefore we analyzed in-depth paired baseline(n=10) and recurrent tumor samples of the lymph nodes(n=10) and brain metastasis (n=2) through Whole Exome Sequencing (WES) analyses. Additionally we incorporated transcriptome sequencing data from 22 patients (21 paired-end samples and one single end sample)

  Study EGAS50000000488

• Immune signature of malignant melanoma in pregnancy

  Melanoma is a highly immunogenic malignancy and there is a deep-rooted notion among clinicians that a probable systemic immunosuppressed state during pregnancy would negatively influence melanoma related prognosis. To test this hypothesis on a more fundamental level, we collected a unique set of melanoma tumor samples and performed RNAseq to draw comparisons between the immune cell infiltrate of pregnant patients and non-pregnant matched controls. We found that there is indeed no differential expression of any immune cell subset. This underscores the notion that the supposed immunosuppressive state of pregnancy does not hamper the anti-tumor immune response.

  Study EGAS50000000492

• human CMV-specific CD8+ T cells

  In this study we established a comprehensive workflow to collect multi-omics single-cell data using a commercially available micro-well based platform. This included whole transcriptome, cell surface markers (targeted sequencing-based cell surface proteomics), T cell specificities, adaptive immune receptor repertoire (AIRR) profiles and sample multiplexing. With this technique we identified novel paired T cell receptor sequences for three prominent human CMV epitopes. In addition, we review the ability of dCODE dextramers to detect antigenspecific T cells at low frequencies by estimating sensitivities and specificities when used as reagents for single-cell multi-omics.

  Study EGAS50000000633

• A non-canonical lymphoblast in refractory childhood T-cell leukaemia

  Refractory cancers may arise either through the acquisition of resistance mechanisms by cancer cells or represent distinct diseases. The origin of childhood T-cell acute lymphoblastic leukaemia (T-ALL) that does not respond to initial treatment, i.e. refractory disease, is unknown. Refractory T-ALL carries a poor prognosis and cannot be predicted at diagnosis. Here, we performed single cell mRNA sequencing of T-ALL from children who did or did not respond to initial treatment. We identified a transcriptionally distinctive blast population, exhibiting features of innate-like lymphocytes, as the major source of refractory disease.

  Study EGAS50000000767

• Oncogene activated human breast luminal progenitors contribute basally located myoepithelial cells

  Basal-like breast cancer originates in luminal progenitors, frequently with an altered PI3K pathway, and focally in close association with genetically altered myoepithelial cells at the site of tumor initiation. The exact trajectory behind this bi-lineage phenomenon remains poorly understood. Here we used a breast cancer relevant transduction protocol including hTERT, shp16, shp53, and PIK3CA(H1047R) to immortalize FACS isolated luminal cells, and we identified a candidate multipotent progenitor. We found that the apparent luminal phenotype of these oncogene transduced progenitors was metastable giving rise to basal-like cells dependent on culture conditions.

  Study EGAS50000000505

• PD-associated regulatory variants in human dopaminergic neurons reveals modulators of SCARB2 and BAG3 expression

  SNPs have been associated with the risk of Parkinson’s disease but not in regulatory regions. While those potentially disrupt TFBS altering gene expression and contributing to cis-regulatory variation. To study changes in A and B compartment interactions and in topologically associated domains (TADs), we sequenced: - 3D chromatin contact using LowC, 6 samples. 3 replicates for each condition: smNPC (controls) cells and differentiated neurons after 30 days. Resulting paired-end are provided as BAM files. In order to confirm the predicted impact of the PD-associated allele of rs144814361 on BAG3 promoter, we proceeded with genome editing of the TH-REP1 cell line by using prime editing to insert the “T” allele at the position chr10:119651405 in the BAG3 promoter. - Chromatin accessibility using ATAC-seq, 9 samples of derived cell line TH-REP1. 3 replicates for each condition: 1) iPSC Wild Type 2) SNP-BAG3 variant in iPSC 3) SNP-BAG3 variant in smNPC. BAG3 variant: heterozygous for the SNP variant: rs144814361 (chr10 119651405) Resulting sequencing are provided as paired-end FASTQ files.

  Dataset EGAD50000002258

• Multiomic characterization of clonotypic B cells

  DNA was purified using AMPure XP magnetic beads (Beckman Coulter [BC] Life Sciences, Indianapolis, IN) and its quality was evaluated in an Agilent 4200 Tapestation using the Genomic DNA ScreenTape system (Agilent, Santa Clara, CA). DNA was quantified using the Qubit System (Invitrogen). Extracted DNA from AL patients was fragmented to 200bp by a Covaris S220 ultrasonicator (Covaris, Woburn, MA) and used to generate and capture libraries following the manufacturer’s indications from Twist Bioscience’s Human Core Exome Enrichment Kit (Twist Bioscience). Extracted DNA from MM patients and HA was fragmented to an average size of 225 bp using a Covaris S220 ultrasonicator (Covaris, Woburn, MA) and subjected to DNA library construction using Chromium Genome Reagent Kit V2 for Exome Assays (10X Genomics). Target enrichment was performed with SureSelectXT Human All Exon V6 Capture Library (Agilent) or SureSelectXT2 Human All Exon V5+UTRs (Agilent), and sequence targets were captured and amplified in accordance with the manufacturer’s protocol. Final libraries were combined with standard Illumina sequencing primers and paired-end sequenced (150bp) on a HiSeq X platform (Illumina, CA) or in a NovaSeq 6000 (Illumina).

  Dataset EGAD50000002162

• Whole exome sequencing (WES) of EBV- primary central nervous system lymphoma (PCNSL)

  This dataset contains whole exome sequencing (WES) of 29 HIV- EBV- primary central nervous system lymphoma (PCNSL) tumors and 5 activated B-cell-like PCNSL (ABC-PCNSL) and activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) cell lines (TK, HKBML, OCI-Ly3, HBL-1, TMD-8). Cases with secondary involvement of the CNS were excluded. DNA was extracted with AllPrep DNA/RNA FFPE kit and libraries were prepared using the Agilent SureSelect Human All Exon v6 + UTR kit. Paired end reads were aligned to GRCh37 using bwa mem v.0.7.17, and reads were sorted and duplicated were marked in the final BAM files. Access to this data is controlled. There are a number of steps that a researcher must take to obtain access to this data, including execution of a Data Access Agreement between the institutions. The process is overseen by the Technology Development Office; please contact our general email address TDOadmin@phsa.ca. Please only click the "request data" button on the EGA website after a Data Access Agreement is fully executed.

  Dataset EGAD50000000451

• ScRNA-seq of human kidney immune cells of patients with ANCA-associated glomerulonephritis, Lupus Nephritis against a healthy nephrectomy control

  ANCA-associated glomerulonephritis (AGN) associates with a high risk of end-stage kidneydisease. The role of kidney immune cells in local inflammation remains unclear. This study investigates kidney immune cell diversity and function. Kidney tissue from AGN patients (n=5) and a lupus nephritis (LN) patient (n=1) were aquired during a biopsy procedure for a clinical indication. Needle-core biopsies were obtained for histopathological examination, and an additional pass was performed to retrieve kidney tissue for scRNA-seq. Healthy kidney tissue (n=1) was obtained from a kidney that was surgically removed do tue due to a (non-invasive) papillary urothelial carcinoma. Immediately after collection, kidney tissue was processed into a single-cell suspension and sorted using a 4-color flow cytometry panel to isolate living, CD45+immune cells. To aid in the multi-omic characterization, surface markers and T and B cell repertoires were sequenced in 2 samples (1 AGN patient and the nephrectomy control). These samples were incubated with an oligo-antibody TotalSeq-C cocktail containing 130 unique cell surface antigens.

  Dataset EGAD50000000229

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

  The abscopal effects of radiation may sensitize immunologically “cold” tumors to immune checkpoint inhibition (ICI). We investigated the immunostimulatory effects of radiotherapy leveraging multi-omic analyses of serial tissue and blood biospecimens (n=293) from a phase 2 clinical trial of stereotactic body radiation therapy (SBRT) followed by pembrolizumab in metastatic non-small cell lung cancer (NSCLC; NCT02492568). Patients with immunologically-cold tumors (low tumor mutation burden, null PD-L1 expression, WNT-pathway mutated) in the SBRT arm had significantly longer progression-free survival compared to ICI alone (P<0.05). Induction of interferon-gamma, interferon-alpha, and antigen processing and presentation gene sets was significantly enriched post SBRT in non-irradiated tumor sites (FDR adjusted P<0.01). Significant on-therapy expansions of new and pre-existing TCR clones in both the tumor and blood compartments were noted in the SBRT arm (P<0.05). These findings support the systemic anti-tumor effects of immuno-radiotherapy and may open a therapeutic window of opportunity to overcome resistance to ICI.

  Dataset EGAD50000000404

• A conserved enhancer in ecDNA-containing Medulloblastoma

  Extrachromosomal DNA (ecDNA) fundamentally reshapes the regulatory landscape of cancer cells by providing a platform for massive oncogene amplification and heightened chromatin accessibility. This research investigates how ecDNA-resident enhancers operate within large-scale molecular hubs to drive potent, long-range transcriptional activation that transcends standard chromosomal boundaries. By analyzing the unique structural configurations of these elements, the work identifies key mechanisms that contribute to rapid tumor evolution and significant phenotypic plasticity. These findings highlight the critical role of non-chromosomal regulatory elements in maintaining oncogenic signaling and suggest new avenues for therapeutic intervention in aggressive, ecDNA-driven malignancies.

  Study EGAS50000001609

• A conserved enhancer in ecDNA-containing Medulloblastoma

  Extrachromosomal DNA (ecDNA) fundamentally reshapes the regulatory landscape of cancer cells by providing a platform for massive oncogene amplification and heightened chromatin accessibility. This research investigates how ecDNA-resident enhancers operate within large-scale molecular hubs to drive potent, long-range transcriptional activation that transcends standard chromosomal boundaries. By analyzing the unique structural configurations of these elements, the work identifies key mechanisms that contribute to rapid tumor evolution and significant phenotypic plasticity. These findings highlight the critical role of non-chromosomal regulatory elements in maintaining oncogenic signaling and suggest new avenues for therapeutic intervention in aggressive, ecDNA-driven malignancies.

  Study EGAS50000001610

• A conserved enhancer in ecDNA-containing Medulloblastoma

  Extrachromosomal DNA (ecDNA) fundamentally reshapes the regulatory landscape of cancer cells by providing a platform for massive oncogene amplification and heightened chromatin accessibility. This research investigates how ecDNA-resident enhancers operate within large-scale molecular hubs to drive potent, long-range transcriptional activation that transcends standard chromosomal boundaries. By analyzing the unique structural configurations of these elements, the work identifies key mechanisms that contribute to rapid tumor evolution and significant phenotypic plasticity. These findings highlight the critical role of non-chromosomal regulatory elements in maintaining oncogenic signaling and suggest new avenues for therapeutic intervention in aggressive, ecDNA-driven malignancies.

  Study EGAS50000001608

• 503 genotypes from Inner Asia used in 'Close inbreeding and low genetic diversity in Inner Asian human populations despite geographical exogamy' publication

  Inner Asia is particularly interesting to understand human history and evolution, as two groups presenting contrasting cultural traits (notably their language, their social organisation and matrimonial system) cohabit. We sampled 503 individuals from these two groups, belonging to 17 populations from 11 distinct ethnic groups (AltaiKizhi, Kazakh, Khakas, Kyrgyz, Mongolian, Shore, Tajik, Telengit, Tubalar, Turkmen and Uzbek). The samples were then genotyped with 5 different DNA-arrays and, after quality-control, the 253,532 autosomal SNPs present in all the arrays were merged together in the present dataset.

  Study EGAS00001002951

• Lethal malformation syndrome

  Identification of the genetic basis of rare monogenic diseases can provide insights into disease mechanisms, biological pathways and potential therapeutic targets. Exome sequencing has proven to be a powerful, efficient strategy for the identification of the genes underlying rare Mendelian disorders. The genetic defect behind the lethal malformation syndrome under study is known in some cases and has proven useful in revealing the primary underlying defect. We have six typical unrelated families with no known mutation. The aim of this study is to identify the locus associated with this lethal malformation syndrome in these families using exome sequencing.

  Study EGAS00001000061

• Genetic determinants of glycated hemoglobin levels in the Greenlandic Inuit population

  We recently showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at investigating the genetic determinants for glycated hemoglobin (HbA1C). We found no novel associations but saw that for 10 out of 15 known HbA1C loci that the effects in Greenlandic Inuit were similar to previously reported. One locus, ANK1, showed a significant ancestral population specific effect. Our results shed light on the genetics effects across ethnicites.

  Study EGAS00001002641

• Novel Epigenetic Markers for Toxicity after Intraoperative and Conventional Radiotherapy for Breast Cancer

  Ionizing radiation is a common treatment option for cancer but its use is limited by the unpredictable and highly heterogeneous onset of late side effects, especially radiation-induced fibrosis. Clinically applicable biomarkers and effective treatments for radiation fibrosis are currently unavailable. In order to identify novel markers we ran a genome-wide DNA methylation screen in primary dermal fibroblasts obtained from breast cancer patients before intraoperative radiotherapy. Cells from patients developing fibrosis within a three-year follow up were compared to those without fibrosis (12 individuals per group). Illumina Infinium HumanMethylation450 BeadChip Technology was used.

  Study EGAS00001001279

• HipSci___RNAseq___Rare_BBS

  The HipSci project brings together diverse constituents in genomics, proteomics, cell biology and clinical genetics to create a UK national iPS cell resource and use it to carry out cellular genetic studies. In this sub-study we perform RNAseq on iPS cells generated from skin biopsies or blood samples from rare disease patients diagnosed with Bardet-Biedl syndrome 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 EGAS00001001318

• Chracterising_cellur_pathways_underlying_CD3_CD28_activation_of_human_CD4__cells

  We devised an approach to disentangle the TCR and CD28 pathways upon stimulation in naive and memory primary human CD4+ T cells (Tcons) in response to defined stimulatory signals. Isolated memory and naïve T cells were activated using anti-CD3, anti-CD28 or both in combination. As a control we cultured cells in the same conditions but without the stimuli. We carried Chipmentation using the H3K27ac antibody on 200,000 cross-linked cells. 1) 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 please see http://www.sanger.ac.uk/datasharing/

  Study EGAS00001002599

• Ibrutinib induces a global chromatin reorganisation in chronic lymphocytic leukaemia

  Chronic lymphocytic leukaemia (CLL) is the most common haematological malignancy in developed countries. Ibrutinib (PCI-32765), a specific and irreversible inhibitor of Bruton's Tyrosine Kinase (BTK) represents a major step forward in the treatment of CLL. We have undertaken a detailed analysis of the changes happening to the chromatin structure in CLL cells from patients continuously receiving oral doses of ibrutinib. ChIP-seq has been performed for H3K4me3, H3K27ac, H3K27me3 and EZH2 . We observed that Ibrutinib-dependent lymphocytosis correlates with a global and transient recruitment of EZH2 to active cis-regulatory elements and increased H3K27me3.

  Study EGAS00001002827

• 502 present-day genotypes included in the '137 ancient human genomes from across the Eurasian steppe' publication

  For thousands of years, the Eurasian steppe has been a centre for human migrations and cultural changes. To understand its population history following the Bronze Age migrations, 137 ancient humans were sequenced. These ancient DNA sequences were notably compared to the genetic data of present-day populations from Eurasia. Besides already published data, 502 individuals currently living in Inner Asia and Jordania were sampled and newly genotyped on diverse DNA-arrays. These new data, merged as a single dataset of 242,406 autosomal SNPs, are included in the present ENA study.

  Study EGAS00001002926

• CCND1-negative MCL

  A subset of CCND1-negative mantle cell lymphoma MCL (CCND1- MCL) has been recognized, and around half of them harbor CCND2 translocations. To identify other potential mechanisms driving MCL pathogenesis we investigated CCND1− MCL by by whole genome/exome sequencing. We identified a cryptic insertion of IGK and IGL enhancer regions near the CCND3 gene in three cases. Specific FISH probes detected 10 additional cryptic IGK juxtapositions to CCND3 (6 cases) and CCND2 (4 cases). In conclusion, virtually all CCND1-/SOX11+ MCL carry CCND2/CCND3 rearrangement with IG genes, including cryptic IGK/L enhancer regions not detected with currently used FISH probes.

  Study EGAS00001003060

• Unraveling metastatic progression of breast cancer

  To reconstruct the trajectories of BC progression, we performed exome sequencing (Illumina HiSeq2000, Truseq DNA sample preparation kit v2 and Exome Enrichment Kit v2; alignement done with BWA, substitutions and indels called with GATK and DINDEL respectively) coupled to validation by Sequenom and deep re-sequencing (ongoing), as well as copy number (CN) analyses (Oncoscan, Affymetrix) on DNA from matched primary (n=1-6/pt), axillary lymph node (ALN, n=1-6 for 4 pts), local recurrence (for 1 pt) and distant metastatic (n=1-5/pt) FFPE samples obtained from an autopsy series of 10 BC pts.

  Study EGAS00001000760

• WXS of 147 lung cancer patients treated with immunotherapy

  We first attempted to predict MHC-binding neoantigens at high accuracy with convolutional neural networks. This prediction model outperformed previous methods in &gt; 70% of test cases. Importantly, our method remarkably increased the predictive value of neoantigen load especially in combination with known resistance parameters. We then developed a classifier that can predict resistance from point mutations that are deleterious to protein function. Notably, genes involved in the adaptive immune response, cytokine signaling,and EGFR signaling held high explanatory power. Furthermore, when integrated with our neoantigen profiling, these anti-immunogenic mutations revealed significantly higher predictive power than known resistance factors.

  Study EGAS00001003781