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• Gene expression QTL mapping in stimulated iPSC-derived macrophages

  Immune cells sense and respond to external stimuli, initiating an inflammatory response, with genetic variants potentially altering these responses. Traditional QTL mapping often uses naïve cells, missing condition-specific variants detectable post-stimulation. Our study uses a high-throughput platform to map eQTLs across 24 conditions using iPSC-derived macrophages, identifying that 76% of eQTLs in stimulated conditions were also present in naïve cells. We found response eQTLs (reQTLs) vary widely across conditions, with rare single-condition reQTLs being overrepresented among disease-colocalizing eQTLs. This study nominates 21.7% more disease effector genes at GWAS loci through reQTL colocalization, with 38.6% not found in the GTEx catalogue, highlighting the importance of condition-specific regulatory variation in understanding disease risk alleles. Our findings underscore the value of condition-specific studies in elucidating the genetic mechanisms underlying complex diseases. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001015380

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

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

  Study EGAS00001004015

• Childhood_arthritis_DNA

  The aim of this study is to describe the transcriptome of single arthritic cells.

  Study EGAS00001002652

• Single_cell_RNA_sequencing_of_rhabdomyosarcoma_tumouroids

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008273

• Single_cell_RNA_sequencing_of_rhabdomyosarcoma_tumour_tissue

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008275

• Single_cell_ATAC_sequencing_of_rhabdomyosarcoma_tumour_tissue

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008276

• De novo modeling of chromoplectic Ewing sarcoma tumors from patient-derived mesenchymal stem cells

  Ewing sarcoma is characterized by pathognomonic translocations fusing most frequently EWSR1 with FLI1 (EF1). In addition, Ewing sarcoma can also display alterations in STAG2, TP53 and CDKN2A (SPC). Starting from Ewing sarcoma derived human mesenchymal stem cells (MSCpat), we recapitulated this translocation and SPC alterations using a CRISPR/cas9 approach and generated a bona fide Ewing sarcoma model (EWIma1) displaying transcriptomic (RNA-seq) and epigenetic (ChIP-seq) hallmarks of EwS.

  Dataset EGAD50000001673

• Genomic Signatures Reveal DNA Damage Response Deficiency in Brain Metastases of Colorectal Cancer

  Brain metastasis (BM) of colorectal cancer (CRC) is rare but lethal and lacks effective therapies or a good understanding of its genomic landscapes. We conduct an analysis of whole-exome sequencing (WES, Illumina HiSeq 2500 sequencing platform) on 11 patient-matched BMs, primary CRC tumours, and adjacent normal tissues; and whole-genome sequencing (WGS, Illumina HiSeq X Ten platform) on 8 patient-matched BMs, primary CRC tumors, and adjacent normal tissues to uncover the whole-genome mutational landscape of colorectal cancer with brain metastasis.

  Dataset EGAD00001005030

• cell-free Nucleosome ChIP-seq

  Dataset includes cell-free ChIP-seq data of 268 samples (from 61 self-declared healthy donors, four patients with acute myocardial infarction, 29 patients suffering from autoimmune, metabolic, or viral liver diseases and 56 metastatic colorectal carcinoma (CRC) patients). DNA libraries preparation is documented in the methods section. Libraries were paired end sequenced by Illumina NextSeq 500 and aligned to the human genome (hg19) using bowtie2 (2.3.4.3) with ‘no-mixed’ and ‘no-discordant’ flags. This dataset includes fastq and BAM files of all samples.

  Dataset EGAD00001006811

• Single-cell bam files and RNA sequencing of viral RNA stocks

  244 infected single-cell alveolar bam files, 48 empty well bam files, and 52 RNA sequencing of amplicons (4 SARS-CoV-2 variants with 12 batches and 4 viral variants pool samples). 244 alveolar single cells were captured over 12 experimental batches and experimental condition is written in metadata uploaded as "infected_cells_final_revision.csv". on github (https://github.com/twkim-0510/SARS-CoV-2_viral_competition). Each bam file name corresponds to the sample_name column of the metadata.

  Dataset EGAD00001009711

• Whole Genome Sequencing of Liver Cancers

  Genomic alterations driving tumorigenesis result from the interaction of environmental exposures and endogeneous cellular processes. With a diversity of risk factors including viral infection, carcinogenic exposures and metabolic diseases, liver cancer is an ideal model to study these interactions. Whole genome sequencing of liver tumors identified 10 mutational signatures showing distinct relationships with environmental exposures, replication and transcription. Transcription-coupled damage was specifically associated with the liver-specific signature 16 and alcohol intake. Flood of indels were identified in very highly expressed hepato-specific genes, likely resulting from replication-transcription collisions. Reconstruction of sub-clonal architecture revealed mutational signature evolution during tumor development exemplified by the vanishing of aflatoxin-B1 signature in African migrants. These findings shed new light on the natural history of liver cancers

  Study EGAS00001002408

• Whole Genome and Exon Capture Sequencing of Bladder Cancers

  One primary bladder cancer and paired peripheral blood sample were subjected to whole genome sequencing on an Illumina HiSeq 2000 platform. This technology was utilized to investigate the genetic basis of a durable remission of metastatic bladder cancer in a patient treated with everolimus, a drug that inhibits the mTOR (mammalian target of rapamycin) signaling pathway. Among the somatic mutations found was a loss-of-function mutation in TSC1 (Tuberous Sclerosis Complex 1), a regulator of mTOR pathway activation. Targeted sequencing using an exon capture and sequencing assay was performed on 13 tumors derived from patients on the same everolimus trial as the index patient and the sequencing data from these tumors is included. TSC1 mutation status was correlated with response to everolimus. The index patient responder tumor and peripheral blood DNA were also subjected to exon capture and sequencing.

  Study phs000535

• Genetic and Genomic Analysis of Primary Human Chondrocytes

  Osteoarthritis (OA) is a common, degenerative joint disease characterized by the gradual breakdown of the cartilage in the joints. Despite osteoarthritis affecting over 500 million individuals, the lack of a comprehensive mechanistic understanding of the disease has greatly hindered the development of adequate treatment options. To address this, we generated RNA-seq, Hi-C, and ATAC-seq data in primary human chondrocytes treated with either PBS as resting or a fibronectin fragment (FN-f) to model the OA chondrocyte phenotype. We mapped expression quantitative trait loci and splicing quantitative trait loci, and performed colocalization with OA GWAS data to identify putative OA risk genes. Integration of ATAC-seq and Hi-C data provided insights into the regulatory mechanisms. This study revealed both expression-based and splicing-based OA risk genes, several of which had not been previously identified in chondrocyte studies.

  Study phs003581

• Evolutionary analysis of pancreatic cancer and coexistent precursor lesions using whole exome sequencing data

  Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. Further, the evolution of these lesions contextualizes the dynamics of advanced stage disease. We analyzed the somatic variants of co-existing pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to a pancreatic cancer. We also found that this multi-step progression generally spans many years. Our data suggest that independent, high-grade pancreatic lesions observed in a histologic cross section often represent a single neoplasm that can spread and colonize the ductal system, accumulating spatial and genetic divergence over time.

  Study EGAS00001002778

• Single-cell analysis reveals transcriptomic and epigenomic impacts on the maternal-fetal interface upon SARS-CoV-2 infection

  During pregnancy, the maternal-fetal interface plays vital roles in fetal development. Its disruption is frequently found in pregnancy complications. Recent works show increased incidences of adverse pregnancy outcomes in COVID-19 patients; however, the mechanism remains unclear. Here, we analyzed the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface. Generating bulk and single-nucleus transcriptomic and epigenomic profiles from COVID-19 patients and control samples, we discovered aberrant immune activation and angiogenesis patterns in distinct cells from patients. Surprisingly, retrotransposons were also dysregulated in specific cell types. Notably, reduced enhancer activities of LTR8B elements were functionally linked to the downregulation of Pregnancy-Specific Glycoprotein genes in syncytiotrophoblasts. Our findings revealed that SARS-CoV-2 infection induced significant changes to the epigenome and transcriptome at the maternal-fetal interface, which may be associated with pregnancy complications.

  Study EGAS00001006263

• DAC: Antisense long non-coding RNAs are deregulated in skin tissue of patients with systemic sclerosis

  Dac EGAC00001000788

• Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis

  Study EGAS00001006781

• 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

• Paediatric IBD Mosaicism

  This is a DNA sequencing study investigating genetic mechanisms underpinning childhood inflammatory bowel disease.

  Study EGAS00001002489

• Whole_genome_sequencing_of_rhabdomyosarcoma_tumouroids

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008270

• Blina_Tumour_project

  The aim of this study is to reconstruct the embryology of childhood tumours.

  Study EGAS00001006486

• Orphan_Tumour_Study_NB_sNuc_WGS

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001006837

• Whole_Genome_sequencing_of_rhabdomyosarcoma_tumour_tissue

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008274

• Somatic mutant selection is altered by prior NOTCH1 mutation in ageing esophageal epithelium

  Authors: Charlotte King1, Emilie Abbie1, Joanna C. Fowler1, Irina Abnizova1, Roshan K. Sood1, Swee Hoe Ong1, Michael W. J. Hall1,2, Faye Lynch-Williams3, Benjamin A. Hall4, Philip H. Jones1,2,5 Abstract: In cancer evolution, genome alterations often occur in a specific order, implying selection depends on the prior clonal genotype 1-3. It is unknown if similar constraints operate in normal epithelia. Here, we mapped mutations in normal mid-esophagus of aged UK subjects. Mutant NOTCH1 clones colonized most of the epithelium by age 60 and above 70 tissue was saturated with mutants under strong competitive selection. Mutant TP53 was more strongly selected in donors over 60 years of age. Samples predominantly mutant for NOTCH1 showed increased selection of NOTCH2 mutants and weaker selection of mutant TP53 compared with samples that were mostly NOTCH1 wild type. In mouse esophagus lacking Notch1 we observed strong selection of mutant Notch2 and other genes not selected in wild type esophagus. In normal ageing esophagus, the first driver mutation may change the trajectory of subsequent somatic evolution by altering mutant selection.

  Dataset EGAD00001015258

• Somatic mutant selection is altered by prior NOTCH1 mutation in ageing esophageal epithelium

  Authors: Charlotte King1, Emilie Abbie1, Joanna C. Fowler1, Irina Abnizova1, Roshan K. Sood1, Swee Hoe Ong1, Michael W. J. Hall1,2, Faye Lynch-Williams3, Benjamin A. Hall4, Philip H. Jones1,2,5 Abstract: In cancer evolution, genome alterations often occur in a specific order, implying selection depends on the prior clonal genotype 1-3. It is unknown if similar constraints operate in normal epithelia. Here, we mapped mutations in normal mid-esophagus of aged UK subjects. Mutant NOTCH1 clones colonized most of the epithelium by age 60 and above 70 tissue was saturated with mutants under strong competitive selection. Mutant TP53 was more strongly selected in donors over 60 years of age. Samples predominantly mutant for NOTCH1 showed increased selection of NOTCH2 mutants and weaker selection of mutant TP53 compared with samples that were mostly NOTCH1 wild type. In mouse esophagus lacking Notch1 we observed strong selection of mutant Notch2 and other genes not selected in wild type esophagus. In normal ageing esophagus, the first driver mutation may change the trajectory of subsequent somatic evolution by altering mutant selection.

  Dataset EGAD00001015259

• Somatic mutant selection is altered by prior NOTCH1 mutation in ageing esophageal epithelium

  Authors: Charlotte King1, Emilie Abbie1, Joanna C. Fowler1, Irina Abnizova1, Roshan K. Sood1, Swee Hoe Ong1, Michael W. J. Hall1,2, Faye Lynch-Williams3, Benjamin A. Hall4, Philip H. Jones1,2,5 Abstract: In cancer evolution, genome alterations often occur in a specific order, implying selection depends on the prior clonal genotype 1-3. It is unknown if similar constraints operate in normal epithelia. Here, we mapped mutations in normal mid-esophagus of aged UK subjects. Mutant NOTCH1 clones colonized most of the epithelium by age 60 and above 70 tissue was saturated with mutants under strong competitive selection. Mutant TP53 was more strongly selected in donors over 60 years of age. Samples predominantly mutant for NOTCH1 showed increased selection of NOTCH2 mutants and weaker selection of mutant TP53 compared with samples that were mostly NOTCH1 wild type. In mouse esophagus lacking Notch1 we observed strong selection of mutant Notch2 and other genes not selected in wild type esophagus. In normal ageing esophagus, the first driver mutation may change the trajectory of subsequent somatic evolution by altering mutant selection.

  Dataset EGAD00001015260

• WES to explore mutational landscape of blood and non blood liquids in female patients with metastatic breast cancer.

  Whole Exome Sequencing (WES) to explore mutational landscape of blood and non blood liquids in female patients with metastatic breast cancer. 11 patients. 86 liquid samples, 11 matched normal samples. Median coverage 67X. Illumina paired-end sequencing. Fastq files are provided. WES from Richard et al., Nature Communications, 2025 low-pass Whole Genome Sequencing (lpWGS) to assess the representativeness of seven body liquids from female patients with metastatic breast cancer. 216 liquid samples, 745 solid samples, 20 matched normal samples. 0.5X coverage. lpWGS from Richard et al., Nature Communications, 2025.

  Dataset EGAD50000001852

• RNAseq profiles from the CheckMate-274 clinical trial

  The dataset contains RNAseq profiles of 370 patients from the CA209-274 clinical trial. The Allprep DNA/RNA FFPE kit was used to simultaneously purify genomic DNA and total RNA from formalin-fixed, paraffin embedded (FFPE) tissue sections. RNAseq libraries (75PE, 50M) were sequenced on Illumina NovaSeq 6000 at a plex-level appropriate to the coverage of 2 × 50 base pair (bp) paired end (PE) 50M reads. Fastq files are included.

  Dataset EGAD50000000793

• A compendium of mutational signatures due to environmental exposures

  Analysis of mutational signatures caused by exposure to known mutagens in human induced pluripotent stem (iPS) cells. A reference human iPS cell-line will be exposed to 100 chemicals known or proposed to be mutagenic. Following exposure to mutagen, cells will undergo a period of recovery before sub clones are generated and sequenced. The progenitor "parental" IPS cell-line will be used to generate reference sequence data, in order to determine the mutational signatures acquired as a result of exposure to different mutagens.

  Dataset EGAD00001005351

• Somatic mutations reveal embryonic genetic bottlenecks generating placental mosaicism

  The human placenta harbours chromosomal aberrations that are absent from the fetus in one to two percent of pregnancies. This confined mosaicism suggests that embryonic genetic bottlenecks exist, which phylogenetically segregate placental tissue. Here, we studied the somatic genetic landscape of human placentas by whole genome sequencing of 86 placental biopsies and of 106 microdissections.

  Dataset EGAD00001006337

• two tables containing RNASeq expression values to patients with RNA-Seq data in the study "Comprehensive genomic characterization of refractory multiple myeloma (H067)"

  two tables containing RNASeq expression values to patients with RNA-Seq data in the study "Comprehensive genomic characterization of refractory multiple myeloma (HIPO_067)". From the bam files gene expression was calculated with the annotation of Gencode.v19. Raw Counts and TPM values are given in one table, the other contains filtered TMM normalized CPM values (genes < 1CPM omitted).

  Dataset EGAD00001008363

• CRISPR iPSC methods paper

  This submission is of the sequencing data used in the CRISPR iPSC methods paper. Specifically it is 3 fastq files that each represent a replicate of an experiment to transduce the Toronto KnockOut CRISPR Library - Version 3 (TKOv3) into inferred pluripotent stem cell (iPSC) derived macrophages. The sequencing is of the guide RNAs from the TKOv3 having been extracted from the transduced iPSC derived macrophages.

  Dataset EGAD00001007020

• WGS short read and 10X linked read sequencing of HR Deficient breast cancers

  A set of tumor/normal paired sequencing experiments, performed in short read WGS and 10X linked read whole genomes. BAM files aligned to hg19 are provided. Sample Alias number and Subject ID reflects patient of origin. T/N distinction discriminates between tumor and normal (peripheral blood) tissue.

  Dataset EGAD00001010326

• RNA sequencing in primary inflammatory (TPP) macrophages treated with a MEK1/2 inhibitor

  This dataset comprises raw RNA sequencing from inflammatory (TPP) macrophages that were treated with the MEK inhibitor PD-0325901 (100nM or 500nM) or vehicle control (n=3 donors). MEK inhibitor or vehicle control was added on day 4 and cells were harvested on day 6 and lysed. RNA was extracted from cell lysates using an AllPrep DNA/RNA Mini Kit (Qiagen). Sequencing libraries were prepared from 10ng RNA using the SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian (Takara) following the manufacturer’s instructions. The quality and molarity of all libraries was assessed using a BioAnalyzer 2100 and the libraries were sequenced on a NextSeq500. Raw data are provided as 50 bp paired-end Illumina reads.

  Dataset EGAD00001011337

• Chromothripsis followed by circular recombination drives oncogene amplification in human cancer

  The mechanisms behind the evolution of complex genomic amplifications in cancer have remained largely unclear. We here identified a type of amplification, termed as “seismic amplification”, that is characterized by multiple rearrangements and discontinuous copy number levels. Seismic amplifications occurred in 9.9% (274/2,756) of cases across 38 cancer types and were associated with massively increased copy numbers and elevated oncogene expression. Reconstruction of the development of seismic amplification revealed a stepwise evolution, starting with a chromothripsis event, followed by formation of circular extrachromosomal DNA that subsequently underwent repetitive rounds of circular recombination. The resulting amplicons persisted as extrachromosomal DNA circles or had reintegrated into the genome in overt tumors. Together, our data indicate that the sequential occurrence of chromothripsis and circular recombination drives oncogene amplification and over-expression in a substantial fraction of human malignancies.

  Study EGAS00001005424

• POPCOL: population-based colonoscopy.

  PopCol is a cohort study in Stockholm, Sweden that includes a data-rich set of individuals with data available from bowel symptoms questionnaires, gastroenterology visits and biospecimens (genotype and 16S sequencing from blood and stool samples, respectively). Genotyping was carried out using the Illumina HumanOmniExpressExome-8v1 arrays at the SciLifeLab NGI facility in Uppsala, Sweden. Fecal DNA was extracted from samples kept at -80°C using Qiagen 5 QIAamp DNA Stool Mini Kits and analyzed using 16S rRNA gene amplicon sequencing (in the V1-V2 hypervariable region). This was performed on the Illumina MiSeq platform at the Institute of Clinical Molecular Biology (IKMB) in Kiel, Germany. Of these, six PopCol participants were PPI users and 12 used antibiotics. The study was approved by the local Committee of Research Ethics (Forskningskommitté Syd) at Karolinska Institutet, Stockholm, in November 2001. Written informed consent was obtained from all participants

  Study EGAS00001004869

• Cell-Free DNA Genomic and Fragmentomic Features for Early Outcome Prediction in Diffuse Large B-Cell Lymphoma

  Purpose: Diffuse large B-cell lymphoma (DLBCL) patients need an accurate and early risk stratification strategy as prompt therapy escalation may improve outcome. Patients and methods: We evaluated cell free DNA (cfDNA) genomic and fragmentomic features in 190 patients with large B-cell lymphoma from more than 40 hospitals in the Benelux using Whole Genome Sequencing (WGS). We defined a new metric called ACT score (Aberrations, Contribution of short fragments, Terminal motif analyses) by combining four cfDNA signals and evaluated its performance to predict end-of-treatment (EOT) response and survival. Results: Individual cfDNA features and ACT score were altered per EOT response after one cycle of treatment (T1). The ACT score at T1 outperformed all individual cfDNA features in predicting EOT response (AUC = 0.74). Patients with a positive ACT score had an inferior outcome compared to ACT score negative patients [progression-free survival (PFS): HR 5.0 (95% CI 3.1-8.2), log-rank test, p < 0.0001) and overall survival (OS): HR 6.5 (95% CI 3.5-12.2), log-rank test, p < 0.0001]. The 2-year PFS in ACT score positive and negative patients were 29.8% and 78.1%, respectively. The prognostic value of the ACT score is independent of the International Prognostic Index and interim imaging. Conclusions: ACT score computed from a single plasma sample collected after one cycle of treatment can predict clinical outcome. This low-cost and easy-to-interpret test does not require tissue biopsies or a priori knowledge of mutations and has the potential to aid patient selection in interventional clinical trials and risk-adapted treatment strategies.

  Study EGAS50000000412

• Whole-exome sequencing of 20 samples of actinic keratosis (10s) and cutaneous squamous cell carcinoma (10s)

  Whole-exome sequencing of 20 samples of actinic keratosis (10) and cutaneous squamous cell carcinoma (10) was performed to investigate a potential relationship between DNA methylation-based subtypes and genetic mutation patterns. 7 samples were shown to belong to the stem cell-like subclass (4 AK and 2 SCC), 12 - to the keratinocyte-like subtype (6 AK and 6 SCC) and one SCC sample is unclassified (was not included in the methylation analysis). Exome regions were captured using Agilent Low Input Exome-Seq Human v5 kit and sequenced on Illumina Hiseq4000 with paired-end 100-nucleotide reads.

  Dataset EGAD00001003765

• Intratumoural Heterogeneity Underlies Distinct Therapy Responses and Treatment Resistance in Glioblastoma

  Glioblastomas are the most common and lethal neoplasms of the central nervous system. Neighbouring glioma cells maintain extreme degrees of genetic and phenotypic variation that forms intratumoural heterogeneity. This genetic diversity allows the most adaptive tumour clones to show treatment resistance and conserve the tumour bulk. We aimed to model this phenomenon and test the effectiveness of several targeted therapeutic interventions to overcome therapy resistance. Heterogenic tumour masses were first deconstructed into single tumour cells, which were expanded independently as single-cell clones. SNP arrays, whole-genome and RNA sequencing, and CpG methylation analysis validated the unique molecular profile of each tumour clone, which displayed distinct pathologic features, including cell morphology, growth rate, and resistance to temozolomide and ionizing radiation. We also identified variable sensitivities to AURK, CDK, and EGFR inhibitors, consistent with the heterogenic molecular alterations that each clone harboured. These targeted therapies effectively eliminated the temozolomide- and/or irradiation-resistant clones and also parental polyclonal cells. Our findings indicate that polyclonal tumours create a dynamic environment that consists of diverse tumour elements and treatment responses. Designing targeted therapies based on a range of molecular profiles can be a more effective strategy to eradicate treatment resistance, recurrence, and metastasis.

  Study EGAS00001003438

• SC_DDD-G-2

  Batch 2 of unfiltered genotype for DDD Study patients (N=8,286), some of which were used in the neurodevelopmental disorder discovery GWAS (Niemi et al., Nature 2018). Samples were genotyped on the Illumina InfiniumCoreExome Beadchip. QC'd data is available in release EGAD00010001604

  Dataset EGAD00010001600

• SC_DDD-G-1

  Batch 1 of unfiltered genotype data for DDD Study patients (N=2,997), some of which were used in the neurodevelopmental disorder discovery GWAS (Niemi et al., Nature 2018). Samples were genotyped on the Illumina HumanCoreExome BeadChip. QC'd data is available in release EGAD00010001604

  Dataset EGAD00010001598

• Congenital anosmia 1

  Congenital anosmias can be complete (the lack of a sense of smell) or specific (the inability to detect specific smells). To date, only a single recessive gene underlying complete anosmia has been identified. Here we sequenced the exomes of 10 individuals from a single family, including three with complete anosmia, across three generations to identify the genetic basis of congenital anosmia in this family. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

  Dataset EGAD00001002210

• Whole Genome Sequencing of Human Organoid Lines (2020-02-20)

  The study will use WGS to aid in benchmarking different culture conditions in a set of genetically annotated human organoid lines. The data will be used to assess whether there is any clonal differences introduced when culturing these lines in different conditions. . This dataset contains all the data available for this study on 2020-02-20.

  Dataset EGAD00001005995

• Intervention with Micronutrients and Long-Term Impact in Brazil-RECODISA

  Intervention with Micronutrients and Long-Term Impact in Brazil, a partnership between the Federal University of Cear&#225;, Brazil and the University of Virginia, USA, enrolled infants in the age group of 2-36 months to investigate trends in gastrointestinal infections and their effects on growth and development and to identify genetic factors contributing to these diseases.A total of 1044 children from six urban communities in Brazil's semiarid region, were enrolled during active surveillance; those with diarrhea (three or more liquid stools in the last 24 hours at enrollment) were defined as a cases and matched with controls having no diarrhea during the past two weeks (at enrollment) to evaluate their growth and development. A subset of 664 children with their genetic and associated phenotypic data is included in this submission. More information on this project and its related projects can be found here: Studies of diarrheal susceptibility, growth, and development, in pediatric populations in Northeastern Brazil

  Study phs003174

• Integrated genetic and epigenetic analysis defines novel molecular clusters in rhabdomyosarcoma

  Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in childhood. To unravel the genetic/epigenetic basis of RMS, we studied 60 RMS cases using whole exome/transcriptome sequencing, copy number (CN) profiling, and DNA methylome analysis. Based on DNA methylation patterns, RMS was clustered into 4 distinct subtypes, which exhibited remarkable correlation with mutation/CN profiles, histological phenotypes, and clinical behaviors. A1 and A2 subtypes, especially A1, largely corresponded to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes were characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite generally poor prognosis in RMS, patients in E1 cluster exceptionally showed excellent prognosis. Our results highlight the close relationship between DNA methylation status and gene mutations and biological behavior in RMS.

  Study EGAS00001000884

• Next Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases

  Putative oncogenic pathways in squamous cell lung cancer have been recently characterized, although their biologic repercussions in patients is largely unknown. This study sought to discover potential clinical manifestations of major pathways in squamous cell lung cancer, particularly the PI3K pathway. Two key findings emerged: patients with stage IV squamous cell lung cancer whose tumors harbored upstream PI3K aberrations had significantly worse survival and a higher burden of metastatic disease. In addition, brain metastases were significantly more common in these patients than in others. Paired lung primary/brain metastasis genotyping, including RNA sequencing and whole exome sequencing, uncovered a high degree of genetic heterogeneity between lung/brain pairs, and identified potential regulators of the metastatic process to brain.

  Study phs000907

• Characterizing TP53 and PPM1D Mutations as Resistance Drivers to Radiation Therapy in Diffuse Intrinsic Pontine Gliomas

  Pediatric high-grade gliomas (pHGGs), encompassing diffuse midline gliomas (DMGs) and hemispheric tumors, represent the most common cause of cancer-related deaths in children age 0-14 years. Over the last decade, several landmark papers have revealed recurrent single nucleotide variants (SNVs) in the core histones H3.3 and H3.1, co-occurring with alterations in the TP53 signaling pathway and receptor tyrosine kinases (RTKs). However, the contribution of structural variants (SVs) to gliomagenesis has not been systematically explored. We performed a comprehensive analysis of whole genome sequencing (WGS) data on pediatric high-grade gliomas (pHGGs) from 179 children, including 61 hemispheric tumors and 118 diffuse midline gliomas, or DMGs, of which 61 are novel to this study. Among the DMGs, 84 (71%) were from pre-treatment biopsies including 33 obtained from the first multi-institutional North American clinical trial to incorporate diagnostic biopsies. This represents the largest cohort of pretreatment DMGs with whole genome sequencing to date. This large cohort of whole genome sequences provides an unparalleled opportunity to assess significantly recurrent structural variants in pHGG and their associations with driver SNVs and SCNAs.&#160;

  Study phs002380

• Bacterial Artificial Chromosomes Establish Replication Timing and Sub-Nuclear Compartment De Novo as Extra-Chromosomal Vectors

  The role of DNA sequence in determining replication timing (RT) and chromatin higher order organization remains elusive. To address this question, we have developed an extra-chromosomal replication system consisting of ~200kb human bacteria artificial chromosomes (BACs) modified with Epstein-Barr virus (EBV) replication origin elements (E-BACs). E-BACs were stably maintained as autonomous mini-chromosomes in both HeLa and human induced pluripotent stem cells (hiPSCs) and established distinct RT patterns. An E-BAC harboring an early replicating chromosomal region replicated early during S phase, while E-BACs derived from RT transition regions (TTRs) and late replicating regions replicated in mid to late S phase. Analysis of E-BAC interactions with cellular chromatin (4C-seq) revealed that the early replicating E-BAC interacted broadly throughout the genome and preferentially with the early replicating compartment of the nucleus. In contrast, mid- to late-replicating E-BACs interacted with more specific late replicating chromosomal segments, some of which were shared between different E-BACs. Together, we describe a versatile system in which to study the structure and function of chromosomal segments that are stably maintained separately from the influence of cellular chromosome context.

  Study phs001520

• Single_cell_RNA_sequencing_of_rhabdomyosarcoma_tumour_tissue

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008271

• Tumor Profiler Project - OV scDNA data

  The dataset contains 10x Chromium single-cell DNA sequencing data from 42 samples from 38 different patients with ovarian cancer. 35 samples were collected from the tumor, and 7 samples from ascites. Sequencing was performed in paired-end mode and sequencing data is provided in fastq format.

  Dataset EGAD50000001291

• INTEGRATIVE MOLECULAR ANALYSIS OF SKIN TUMORS FROM CYLD CUTANEOUS SYNDROME PATIENTS

  CYLD cutaneous syndrome (CCS) is a rare autosomal dominant disorder characterized by germline CYLD mutations and by multiple benign skin tumors dependent on NF-kB pathway. We assembled a large cohort of CCS rare skin tumors that was profiled with whole exome or genome sequencing, RNA sequencing and methylation arrays to better understand genetic mechanisms of CCS tumorogenesis.

  Dataset EGAD50000000362

• Methylome profiling of Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) and a patient derived cell-line model

  Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma associated with NAB2-STAT6 gene fusions. This study established and characterized a novel SFT/HPC patient-derived cell line called SFT-S1 using the twist human methylome panel.

  Dataset EGAD50000000040

• EMBARCAM BC360 PROJECT

  This dataset is related to the EMBARCAM BC360 PROJECT. A total of 106 breast cancer samples, from Pregnancy-Associated Breast Cancer (PABC) (n=57) and non-PABC (n=49) patients, were analysed using the nCounter Breast Cancer 360 V2 panel on the NanoString platform. All samples were FFPE tumor samples from breast cancer patients, derived from GEICAM/2012-03, GEICAM/2017-07, and EpiGEICAM studies, sponsored by GEICAM.

  Dataset EGAD00010002709

• Naive B-cell receptor heavy chain repertoire of celiac patients and healthy controls

  High throughput sequencing dataset of antibody repertoires from naive B-cells, taken from blood samples of 100 individuals from Norway. 48 healthy controls and 52 patients with celiac disease. Sequencing was performed using a 300*2 paired-end kit by Illumina MiSeq. The sequences were processed using pRESTO. Each fastq file in the dataset is the repertoire of a single individual.

  Dataset EGAD00001004512

• Congenital Heart Disease in UK Families

  This project aims to identify highly penetrant coding variants increasing the risk of Congenital Heart Disease (CHD) performing whole exome sequencing on DNA samples from 23 affected individuals, selected from 10 families with presumed Autosomal Recessive Inheritance. This is a collaboration with Prof. Eamonn Maher and Dr. Chirag Patel from the Department of Medical and Molecular Genetics, University of Birmingham plans to sequence 23 indexed Agilent whole exome pulldown libraries on 75Bp PE HiSeq (Illumina)

  Dataset EGAD00001000343

• Resistance to MAPK-inhibitor induces internal duplication in BRAF_Oscar Krijsman

  2 BRAFV600E cell lines that have been made resistance to 1. the BRAF inhibitor PLX4720 and 2. the combination therapy of dabrafenib and trametinib seem to have a internal duplication in the kinase domain. We would like to know if this is caused by a translocation.

  Dataset EGAD00001001846

• RNA-seq from in vivo experiments

  RNA sequencing from 12 xenografts implanted using MSTO-211H cell line and treated with vehicle solution, cisplatin + pemetrexed, or palbociclib (N = 4, each). RNA-seq prepared using TruSeq Stranded mRNA libraries and sequenced with Illumina HiSeq 4000. Data is in raw fastq format, paired end. Some samples have been split in two lanes, with a final count of 34 fastq files.

  Dataset EGAD00001007739

• DNA methylation (MCIP-seq) of human acute leukemias and healthy donors

  MCIP-seq of 77 primary samples obtained from human acute leukemias, namely AML, T-ALL and mixed myeloid/lymphoid leukemias with CpG Island Methylator Phenotype (CIMP). Moreover, MCIP-seq of CD34+ HSPCs from 3 healthy donors is included.

  Dataset EGAD00001011052

• Whole exome sequencing (WES)

  The whole study comprises of two patient cohorts. Screening cohort: 40 patients of Germany; validation cohort: 40 patients from Asia. Further, bile duct and CCA cell lines have been analyzed. This dataset contains whole exome sequencing data of 37 tumor/normal pairs from the screening cohort plus an additional relapse tumor of one of those 37 patients. Data was generated on Illumina HiSeq 2000 device in paired-end mode and is stored in BAM file format.

  Dataset EGAD00001011324

• Carbamazepine-induced hypersensitivity reactions in Europeans

  An antiepileptic drug carbamazepine is well tolerated by the majority of patients, but can cause severe and potentialy fatal hypersensitivity reactions in a small number of individuals. The aim of this study was to identify genetic predictors of hypersensitivity reactions to carbamazepine. We undertook a genome-wide association study (GWAS) in 22 patients of European ancestry with carbamazepine-induced hypersensitivity syndrome (HSS) and compared our data with genotypes from a healthy population within the WTCCC. We performed imputation of classical HLA alleles according to a recently described method (Science. 2010 Dec 10;330(6010):1551-7. Epub 2010 Nov 4). GWAS statistical analysis was performed using logistic regression with an additive model of inheritance.

  Study EGAS00000000037

• Genome-wide evaluation of the maturation of the immune response to the tuberculin skin test from day 2 to day 7

  The tuberculin skin test (TST) is a standardised human challenge model to evaluate the immune response to Mycobacterium tuberculosis (Mtb) antigens in vivo. To study the temporal evolution of the TST, we recruited healthy volunteers with evidence of peripheral blood Mtb reactive T cells, to undergo a TST in each arm that was sampled on day 2 at one site and on day 7 at the contralateral site on day 7. Genome-wide TST transcriptomes at day 2 and day 7 were defined by differential gene expression compared to transcriptomes from the site of control saline injections performed in a separate subset of volunteers.

  Study EGAS50000000822

• Transposable elements are co-opted as oncogenic regulatory elements by lineage-specific transcription factors in prostate cancer

  Study EGAS00001007188

• ChIPseq sequence of liver cancer

  There are 61 samples

  Dataset EGAD00001009842

• WES and RNAseq of Simultaneous Bilateral Breast Cancer

  This dataset includes NGS profiling of 13 women with simultaneous bilateral breast cancer. Seven women have WES of untreated surgical resections and matched healthy tissue. The six other women have WES of healthy tissue, WES+RNAseq of pre-neoadjuvant tumor biopsies, and when residual disease was present (6 tumors in 4 patients), WES+RNAseq of residual disease from post-neoadjuvant therapy surgery. One patient from the WES+RNAseq cohort had multifocal bilateral disease at diagnosis so there are 2 pre-neoadjuvant biopsy samples from each breast.

  Dataset EGAD00001009987

• Ribo-Seq dataset of Targeting the dark proteome to expand the lineage-retained antigen landscape in neuroblastoma

  This dataset contains ribosome profiling (Ribo-seq) data generated to map actively translated open reading frames, including non-canonical ORFs from the "dark proteome", in neuroblastoma, supporting the identification of translation-validated tumor antigens. Ribosome-protected mRNA fragments (~28–30 nt) were isolated from 47 neuroblastoma samples comprising cell lines, patient-derived tumoroids, and primary patient tumors spanning the adrenergic (ADRN) and mesenchymal (MES) lineage states. Libraries were prepared following a modified version of the McGlincy &amp; Ingolia 2017 protocol and sequenced single-end (1x50 bp) on the Illumina NextSeq 2000 platform. Raw data are provided as single-end fastq.gz

  Dataset EGAD00001016123

• MutWP5: CRUK Mutographs of Cancer: Cancer Mastectomy (Exome)(Novaseq)

  Sequencing of LCM-derived microbiopsies from 40 women who underwent mastecomies due to breast cancer. LCM and sequencing will be conducted on both normal, unaffected breast, and, where possible, tumour tissue. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue, and compare findings between the normal and associated cancer tissues. Whole-genome sequencing will be conducted on samples identified as promising from the initial targeted data. Results from this poriton of the study will be compared to women who had cosmetic breast reduction surgeries and those who are BRCA carriers. . This dataset contains all the data available for this study on 2023-03-08.

  Dataset EGAD00001010117

• Dataset for Sarcoma RNA sequencing linked from study EGAS00001004813

  Sequencing data of 410 sarcoma tumor runs, which were uploaded to EGAS00001004813. The sequencing was always paired.

  Dataset EGAD00001010276

• Molecular Profiling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases

  There is a critical need to improve our understanding of the pathogenesis of -melanoma brain metastases (MBM). Thus, we performed RNA sequencing on 88 resected MBMs and 42 patient-matched extracranial metastases; tumors with sufficient tissue also underwent whole-exome sequencing, T-cell receptor sequencing, and IHC. MBMs demonstrated heterogeneity of immune infiltrates that correlated with prior radiation and post-craniotomy survival. Comparison with patient-matched extracranial metastases identified significant immunosuppression and enrichment of oxidative phosphorylation (OXPHOS) in MBMs. Gene-expression analysis of intracranial and subcutaneous xenografts, and a spontaneous MBM model, confirmed increased OXPHOS gene expression in MBMs, which was also detected by direct metabolite profiling and [U-13C]-glucose tracing in vivo IACS-010759, an OXPHOS inhibitor currently in early-phase clinical trials, improved survival of mice bearing MAPK inhibitor-resistant intracranial melanoma xenografts and inhibited MBM formation in the spontaneous MBM model. The results provide new insights into the pathogenesis and therapeutic resistance of MBMs.

  Study EGAS00001003672

• WGS of 78 FL tumour normal pairs

  This dataset is the second batch of WGS uploaded from FL GenomeCanada data. The other batch is in EGAD00001011343

  Dataset EGAD50000000253

• Crohn_s_Exome_Sequencing

  The aim is to find rare variants of intermediate penetrance in those at risk of Crohn's disease

  Study EGAS00001000385

• Liver_Tumours_WGS

  The aim of this study is to define the mutational landscape of human liver tumours.

  Study EGAS00001003446

• Orphan_Tumour_Study___RNAseq

  The aim of this study is to study the genomes of ultra rare childhood tumours

  Study EGAS00001002534

• Whole_Genome_sequencing_of_rhabdomyosarcoma_tumour_tissue

  The aim of this study is to investigate the genomic landscape of human cancer.

  Study EGAS00001008277

• Genetic mutation profiling of lymphomas arising in the uterine cervix and vagina

  Follicle center lymphoma (FCL) of the lower female genital tract (LFGT) is a rare lymphoma, with fewer than 20 cases reported to date. Since the genetic features of FCL of the LFGT have not been well characterized, we aimed to identify genetic alterations in this tumor through whole-exome sequencing or targeted gene panel analysis. Genomic DNA was extracted from a frozen tissue sample obtained from a surgically resected uterine cervical tumor. Whole-exome sequencing was performed using the Illumina NovaSeq X Plus platform. Library preparation was conducted with the SureSelect Human All Exon V6 kit, and sequencing was carried out with 150 bp paired-end reads.

  Study JGAS000823

• Sequence data to study genomic CNVs that drive apoptotic resistance and relapses on immune checkpoint inhibitors

  This project investigates the genomic mechanisms underlying acquired resistance to immune checkpoint inhibitors (ICIs) across tumor types, addressing the critical clinical problem of treatment relapses where the molecular basis remains poorly understood. Through integrative genomic analyses of longitudinal clinical melanomas, functional CRISPR-Cas9 screens, and human and murine melanoma models, the study demonstrates that copy-number variant (CNV)-driven subclonal evolution is a primary driver of clinical relapses. The research identifies resistance-driver genes targeted by CNVs, including pro-apoptotic gene deletions and anti-apoptotic gene amplifications, which collectively downregulate apoptotic priming in resistant cells. The findings establish that modulating the apoptotic threshold can prevent or reverse ICI resistance, positioning CNV evolution as a key driver of acquired resistance and identifying apoptotic regulation as a therapeutic target to combat resistance evolution.

  Study EGAS50000001055

• Somatic mutations, clonal architecture and genomic evolution in multiple myeloma

  Multiple myeloma is an incurable plasma cell malignancy whose molecular pathogenesis is incompletely understood. We used whole exome sequencing, copy number profiling and cytogenetic to analyses 84 samples from 67 patients with myeloma. In addition to known myeloma genes, we identify new candidate genes, including truncations of SP140, ROBO1 and FAT3 and clustered missense mutations in EGR1. We find oncogenic mutations in cancer genes not previously implicated in myeloma, including SF3B1, PI3KCA and PTEN. We define diverse processes contributing to the mutational repertoire, including kataegis and somatic hypermutation. Most cases have at least one cluster of subclonal variants, including subclonal driver mutations, implying on-going tumor evolution. Serial samples revealed diverse patterns of clonal evolution, including linear evolution, differential clonal response and branching evolution. Our findings reveal the myeloma genome to be heterogeneous across patients and, within individual patients, to exhibit diversity in clonal admixture and dynamics in response to therapy.

  Dataset EGAD00001000339

• H3K27ac ChIP-seq in TMPRSS2:ERG positive and negative prostate cancer tissue samples

  The TMPRSS2:ERG (T2E) structural rearrangements typifies ~50% of prostate tumors and results in overexpression of the ERG transcription factor. Using chromatin data collected in T2E and non-T2E primary prostate tumors, we show a distinct cis-regulatory landscape between T2E and non-T2E, inclusive of Cluster Of Regulatory Elements (COREs). This is mediated by ERG co-option of HOXB13 and FOXA1 implementing a T2E-specific transcriptional profile. We also report a T2E-specific CORE on the structurally rearranged ERG locus arising from spreading of the TMPRSS2 locus pre-existing CORE, assisting in its overexpression. Finally, we show that the T2E-specific cis-regulatory landscape reveals a vulnerability against the NOTCH pathway. Taken together, our work shows that overexpressed ERG co-opts master transcription factors to deploy a unique cis-regulatory landscape inducing a druggable dependency on NOTCH signaling in T2E prostate tumors.

  Study EGAS00001002496

• RNA bulk sequencing on organoids from different organs with or without TS2/16 antibody

  RNA bulk sequencing on organoids from colon, ileum, jejunum, duodenum and pancreas duct with or without TS2/16 antibody. Also there is difference in extracellular matrix used, BME vs Colagen.

  Dataset EGAD50000001606

• Pediatric HGG panel sequencing

  Targeted glioma panel sequencing of pediatric hemispheric high-grade gliomas and diffuse midline gliomas. File type is paired-read fastq files (2 per sample). Sequencing was performed on Illumina NextSex instruments. Genes covered: TP53, H3F3A, HIST1H3B, HIST1H3C, IDH1, IDH2, KRAS, PIK3CA, TERT promoter, PTPN11, FGFR1/2/3, MYB, BRAF, MYBL1, EGFR, PDGFRA, MYCN, MYC, CDKN2A.

  Dataset EGAD50000000326

• WGS of human colorectal cancer organoid exposed to genotoxic pks+ E. coli

  Organoid cultures were exposed to two different E.Coli strains and a dye control with three biological duplicates. Their original culture was harvested as a control. In total 10 organoid cultures were whole-genome sequenced using the Novaseq6000 platforms. The data is deposited as .bam format.

  Dataset EGAD00001005416

• Whole Exome Sequencing of a Chinese Cataract Girl

  Whole exome sequencing of a Chinese girl with congenital cataract. The dataset contains one sample with two fastq files. The novel PAX6 mutation (c.221G&gt;A) is associated with congenital cataract, and the WFS1 mutation (c.2070_2079del) interactively aggravates this process.

  Dataset EGAD00001008267

• RNA sequencing of T-LGLL patients

  RNA sequencing was performed on 15 T-LGLL patients and five control samples. The raw data is provided as fastq files.

  Dataset EGAD00001008408

• Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome

  Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis. The methylation profile matched strongly with HGAP and sequencing identified somatic FGFR1 and NF1 variants and a PTPN11 germline pathogenic variant. Therapeutic targets were identified but also alterations novel to HGAP such as differential expression of VEGFA and PD-L1. The germline PTPN11 finding has not been previously described in individuals with HGAP.  This case underscores the power of precision medicine from a diagnostic, therapeutic and clinical management perspective, and describes an association between HGAP and NS which has not previously been reported.

  Study EGAS00001007937

• MPNST

  These are only the whole exome sequences

  Dataset EGAD00001001031

• tFL with a PMBL GE signature

  We investigated the clinicopathologic features of 5 follicular lymphomas (FL) that transformed to morphologic diffuse large B-cell lymphomas (DLBCL) and had a primary mediastinal large B-cell lymphoma (PMBL)-like gene expression profile. None of the transformed FL (tFL) arose in the mediastinum, all cases tested had a germinal center B-cell immunophenotype, 20% were CD30+, 60% CD23+, 80% MAL+, 20% CD200+, and 0% CD273/PDL2+. Whole exome sequencing detected alterations in genes associated with both FL/DLBCL (CREBBP, KMT2C, KMT2D, ARID1A, HIST1 members, and TNFRSF14) and PMBL (JAK-STAT pathway genes, B2M, and CD58). Copy number (CN) analysis detected gains/amplification of REL in 60% and STAT6 in 40%, gains of chromosome 16, including IL4R, in 40%, and both deletions and gains of 11q in 20%. This cohort, although limited in size, supports a subset of tFL that has blended features between FL/DLBCL and PMBL. Despite having some features that are less common in DLBCL (MAL and CD23 expression, JAK-STAT activation), these cases lack the most characteristic CN alteration seen in PMBL (9p24.1 gain/amplification). This cohort expands the biologic heterogeneity of tFL, illustrating a subset with blended FL/DLBCL and PMBL features, with potential treatment implications that include the use of novel PMBL-targeted therapies.

  Study EGAS00001005870

• Molecular Profiling of Gallbladder Cancer (MPOG)

  The purpose of this study is to investigate the underlying genetic factors involved in gallbladder cancer.

  Study phs001404

• IDH1 Somatic Mutation Profile in Intrahepatic Cholangiocarcinoma

  The objective of this study is to identify somatic IDH1 mutations in intrahepatic cholangiocarcinoma samples.

  Study EGAS50000001638

• Psoriatic_arthritis

  This is a pilot single cell mRNA sequencing experiment to study immune cells in psoriatic arthritis.

  Study EGAS00001002104

• Benchmarking_CRISPR_Whole_genome_Drop_out_Screen___B_S

  This study is a benchmarking exercise to explore potential source of variation between different CRISPR drop out libraries.

  Study EGAS00001002931

• Variation and transmission of the human gut microbiota across generations - shotgun data

  Although composition and functional potential of the human gut microbiota evolve over lifespan, kinship has been identified as a key covariate of microbial community diversification. To date, sharing of microbiota features within families has however mostly been assessed between parents and their direct offspring. Here, we investigate potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (N=102) spanning three to five generations over the same female bloodline. We observe microbiome community composition to be associated with kinship, with seven (low-abundant) genera displaying familial distribution patterns. While kinship and current cohabitation emerged as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother-daughter pairs, decreasing with increasing daughter’s age, and being higher among cohabiting pairs than those living apart. Although rare, we do detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation.

  Study EGAS00001005649

• Variation and transmission of the human gut microbiota across generations - 16S data

  Although composition and functional potential of the human gut microbiota evolve over lifespan, kinship has been identified as a key covariate of microbial community diversification. To date, sharing of microbiota features within families has however mostly been assessed between parents and their direct offspring. Here, we investigate potential transmission and persistence of familial microbiome patterns and microbial genotypes in a family cohort (N=102) spanning three to five generations over the same female bloodline. We observe microbiome community composition to be associated with kinship, with seven (low-abundant) genera displaying familial distribution patterns. While kinship and current cohabitation emerged as closely entangled variables, our explorative analyses of microbial genotype distribution and transmission estimates point at the latter as a key covariate of strain dissemination. Highest potential transmission rates are estimated between sisters and mother-daughter pairs, decreasing with increasing daughter’s age, and being higher among cohabiting pairs than those living apart. Although rare, we do detect potential transmission events spanning three and four generations, primarily involving species of the genera Alistipes and Bacteroides. Overall, while our analyses confirm the existence of family-bound microbiome community profiles, transmission or co-acquisition of bacterial strains appears to be strongly linked to cohabitation.

  Study EGAS00001005651

• Comprehensive genomic characterization of early stage bladder cancer - Total RNA-seq data

  This study looks at the non muscle invasive bladder cancer subtypes based on totRNAseq data of 414 bladder cancer samples collected in different European centers within the UROMOL project. All samples were sequenced using paired reads on Illumina platforms. The reads are mapped to hg38.

  Study EGAS50000000512

• Employing_single_cell_sequencing_for_detection_of_mutational_signatures_reflecting_on_going_mutagenesis_

  12 single cells will be sequenced from a previously single-cell derived clone of a JSC-1 cell line. Additional 12 single cells are likely to be sequenced from a previously single-cell derived clone of a SW756 line. Both belong to CGP’s panel of approximately 1000 human cancer cell lines.

  Study EGAS00001002679

• Somatic mutation and selection at epidemiological scale - TwinsUK_TargetedNanoSeq_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).As we age, many tissues become colonised by microscopic clones carrying somatic driver mutations. Some of these clones represent a first step towards cancer whereas others may contribute to ageing and other diseases. However, our understanding of the clonal landscapes of human tissues, and their impact on cancer risk, ageing and disease, remains limited due to the challenge of detecting somatic mutations present in small numbers of cells. Here, we introduce a new version of nanorate sequencing (NanoSeq), a duplex sequencing method with error rates of less than 55 per billion base pairs, which is compatible with whole-exome and targeted gene sequencing. Deep sequencing of polyclonal samples with single-molecule sensitivity enables the simultaneous detection of mutations in large numbers of clones, yielding accurate somatic mutation rates, mutational signatures and driver mutation frequencies in any tissue. Applying targeted NanoSeq to 1,042 non-invasive samples of oral epithelium and 371 samples of blood from a twin cohort, we found an unprecedentedly rich landscape of selection, with 46 genes under positive selection driving clonal expansions in the oral epithelium, over 62,000 driver mutations, and evidence of negative selection in some genes. The high number of positively selected mutations in multiple genes provides high-resolution maps of selection across coding and non-coding sites, a form of in vivo saturation mutagenesis. Multivariate regression models enable mutational epidemiology studies on how carcinogenic exposures and cancer risk factors, such as age, tobacco or alcohol, alter the acquisition and selection of somatic mutations. Accurate single-molecule sequencing has the potential to unveil the polyclonal landscape of any tissue, providing a powerful tool to study early carcinogenesis, cancer prevention and the role of somatic mutations in ageing and disease.

  Dataset EGAD00001015618

• WES data from 438 tumor/germline samples with non muscle invasive bladder cancer

  A better understanding of the molecular landscape of non-muscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and identify potential therapeutic targets. Here, we perform a comprehensive genomic analysis of patients diagnosed with NMIBC based on whole-exome- (n=438), shallow whole-genome- (n=362), and total RNA-sequencing (n=414). This dataset contains 876 BAM files corresponding to the full WES dataset. Tumor and matched germline DNA were sequenced to a mean coverage of 132x (35x-338x) and 128x (31x-302x), respectively.

  Dataset EGAD50000000730

• RNA sequencing data of pediatric T-cell acute lymphoblastic leukemia (set 2)

  The dataset includes RNA sequencing FASTQ files from a diagnostic tumor sample and from a relapse sample from tonsil of one T-ALL patient (ALLT-317). Data from the relapse sample from bone marrow of this patient is in set 1 of this submission. TruSeq Stranded Total RNA Library Prep (Illumina) kit was used in library preparation, and Novogene's internal method was utilized in rRNA removal. The diagnostic and relapse tumor samples were sequenced using Illumina Novaseq X Plus, and the target sequencing depth was 21 Gb per sample.

  Dataset EGAD50000002585

• Deciphering Developmental Disorders (DDD)

  The Deciphering Developmental Disorders (DDD) study is a research collaboration between the Wellcome Trust Sanger Institute, the NHS clinical genetics services and families across the UK and Ireland. The project aims to improve the diagnosis of children with developmental disorders by using high-resolution microarray and massively parallel sequencing technologies on 12,000 children and their parents. Genetic changes that explain the child's symptoms will be displayed in the DECIPHER database (https://decipher.sanger.ac.uk). Extended datasets generated by the DDD project will be available in the European Genome-Phenome Archive with access carefully managed by a Data Access Committee.

  Study EGAS00001000775

• Single-nucleus brain transcriptomics reveals microglia dysfunction in Multiple System Atrophy

  Multiple System Atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson’s disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology underlying multiple system atrophy (MSA) or Parkinson's disease (PD), we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Using 10x Genomics Chromium Next GEM Single Cell 3' Reagent Kits v3.1, we isolated 130k nuclei covering all major cell types of the striatum. We performed state-of-the-art bioinformatic analyses on the data followed by orthogonal analyses to validate our findings. We identified a disease-specific activation of microglia cells distinguishing the two diseases and possibly explaining some of the detrimental effects observed in both.

  Study EGAS50000001406

• Genome-wide cell-free DNA biological patterns in patients with cancer

  The structure of cell-free DNA (cfDNA) is altered in the blood of cancer patients. From whole genome sequencing we retrieved the cfDNA fragment-end composition using a new software (FrEIA), as well as the cfDNA size and tumor fraction in three independent cohorts (n=925 cancer from &gt;10 types and 321 control samples). At 95% specificity, we detect 72% of cancer samples using at least one cfDNA measure, including 64% of early-stage cancer (n=220). cfDNA detection correlates with a shorter overall (p=0.018) and recurrence-free (p=0.006) survival in patients with resectable esophageal adenocarcinoma. Integrating cfDNA measures with machine learning in an independent test set (n=396 cancer, 90 controls) achieve a detection accuracy of 82% and AUROC of 96%. In conclusion, harnessing the biological features of cfDNA can improve at no-extra cost the diagnostic performance of liquid biopsies.

  Study EGAS00001007400

• cfDNA sWGS BAM — Healthy donors

  Paired-end shallow whole-genome sequencing (sWGS) of plasma cfDNA from healthy donors recruited at EFS Montpellier (France). Libraries: DSP (NEBNext Ultra II) and/or SSP (IDT/Swift Accel-NGS 1S Plus). Sequencing by IntegraGen (France, 2022–2024). Reads aligned to GRCh38 (hg38 canonical) with BWA-MEM; BAMs coordinate-sorted and indexed; submission contains primary mapped reads only (unmapped/secondary/supplementary/duplicates removed; typical filter “-F 3332”, MAPQ threshold as noted in analysis records). Each BAM/BAI pair is linked to its Sample and Experiment. Data Use: controlled access.

  Dataset EGAD50000001880