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• Evaluating the immune response in treatment-naive hospitalised patients with influenza and COVID-19

  Clinical characteristics and peripheral blood were acquired upon hospital admission from two well characterised cohorts, a cohort of patients infected with influenza and a cohort of patients infected with SARS-CoV-2 during the first wave of the pandemic and prior to availability of COVID-19 treatments and vaccines.

  Study EGAS00001005971

• CRISPR/Cas9-mediated genome editing of Schistosoma mansoni acetylcholinesterase

  Here we report successful gene knock-in (KI) in the eggs of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We targeted the acetylcholinesterase (AChE) gene of S. mansoni using two synthetic guide RNAs (gRNAs), X5 and X7, respectively. Liver eggs of S. mansoni were exposed to CRISPR-vector containing X5 or X7 by electroporation. Simultaneously, eggs were transfected with a ssODN donor encoding a stop codon in all six frames. Next generation sequencing analysis revealed that CRISPR/Cas9-mediated editing in S. mansoni eggs resulted in Homology-Directed Repair (HDR) when template DNA ssODN provided. Furthermore, soluble egg antigen (SEA) from AChE-modified eggs exhibited markedly reduced AChE activity compared with controls, indicative that programmed Cas9 cleavage mutated the AChE gene. Following injection of modified schistosome eggs into the tail veins of mice, a significant decrease in granuloma size in the lungs of these animals. Notably, an enhanced Th2 response induced by eggs in lung, and splenocytes small intestine-draining mesenteric lymph node cells was also generated in mice injected with X5-KI eggs in different methods. These findings further demonstrate the power and utility of CRISPR/Cas9-based genome editing for undertaking functional genomics studies in schistosomes.

  Dataset EGAD00001006573

• Mitochondria Optimized 10x data

  Optimized 10x library to increase the coverage of the mitochondrial genome from 3’ 10x gene expression data. See details of the experimental method in the methods section of the manuscript

  Dataset EGAD00001010191

• Alternative splicing isoforms in patient-derived hepatocellular carcinoma cells

  The aim of this study was to obtain a landscape of alternative splicing (AS) in human hepatocellular carcinoma (HCC). We applied hybrid sequencing by integrating Pacbio long-read and Illumina short-read RNA sequencing data from 8 patient-derived HCC cell lines, and used an immortalized hepatocyte cell line as reference. This study revealed features of annotated and novel splice variants in HCC cells, including transcript length, AS type and protein changes. We also identified novel isoforms and tumor specific isoforms, which may represent potential biomarkers and targets for therapeutic development.

  Study EGAS00001002697

• Single Cell Genome Variation Induced by Mutational Processes in Cancer - HGSOC Trios Study

  Mutational signatures derived from whole genome sequencing have potential prognostic significance. Identification of high grade serous ovarian cancer patients with deficiency in homologous recombination repair pathways could identify a subset of patients that would benefit from homologous recombination deficiency-specific treatments independent of identification of a pathological BRCA1/2 gene mutation. Clinical protocols rely on a pathologist's assessment of formalin-fixed paraffin-embedded (FFPE) tissues, and thus FFPE tissue samples are readily available. However, the bulk of mutational signature analyses have been performed on fresh frozen tissues. In this study, we aimed to assess the reliability of whole genome sequencing, variant calling, and mutational signature analysis from FFPE tissue samples.

  Study phs003036

• Deregulation of DUX4 and ERG in acute lymphoblastic leukemia

  Chromosomal rearrangements deregulating hematopoietic transcription factors are common leukemia-initiating lesions in acute lymphoblastic leukemia (ALL). Here, we show that deregulation of the homeobox transcription factor gene DUX4 and the ETS transcription factor gene ERG are hallmarks of a subtype of B-progenitor ALL with a distinct gene expression profile that comprises up to 7% of B-ALL. DUX4 rearrangement and overexpression is present in all cases, and is accompanied by profound transcriptional deregulation of ERG, frequent ERG deletion and expression of a truncated ERG isoform, ERGalt. ERGalt utilizes a non-canonical first exon that is bound by DUX4 and induces its expression....

  Study EGAS00001001923

• Somatic L1 retrotransposition in normal colorectal epthelium

  Throughout an individual’s lifetime, genomic alterations accumulate in somatic cells. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome, is poorly understood in normal cells. Here, we explored the whole-genome sequences of 406 normal colorectal clones, 12 MUTYH-associated adenomatous clones, and 19 matched colorectal cancer tissues. In addition, we analyzed promoter DNA methylation status of retrotransposition-competent L1 (in 139 clones) and read-through RNA expression profiles (in 116 clones) to investigate the epigenetic regulation of L1 activity.

  Dataset EGAD00001010183

• Genome-wide association study of response to warfarin in a UK prospective cohort

  Genome-wide association study of Warfarin dosing in 714 British, recruited in Liverpool and Birmingham. Three phenotypes were investigated: warfarin mean dose, warfarin mean stable dose, and INR over 4 during first week of treatment. Stability was defined by at least three INR measurements within target in a three week period. The samples were genotyped on the Illumina 610K chip and imputed using Impute v2.1, with a combined filtered set composed of HapMap 3 release 2 and 1000 genomes pilot 1 CEU.

  Study EGAS00001001130

• Total exRNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects

  We sequenced small RNAs from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 college athletes ages 18-25 years. Many of the participants provided more than one sample, weeks or months apart, allowing us to assess variability in an individual's exRNA expression levels over time. Several individuals provided all three biofluid types at one time, producing data on individual expression levels across several biofluid types. Here we provide a systematic analysis of small exRNAs present in each biofluid, as well as an analysis of exogenous RNAs. We find that a large number of RNA fragments in plasma (63%) and urine (54%) have sequences that are assigned to YRNA and tRNA fragments respectively. Surprisingly, while many miRNAs can be detected, there are few miRNAs that are consistently detected in all samples from a single biofluid. Additionally, we performed whole transcriptome sequencing on 134 plasma and 115 urine samples and identified circRNA.

  Study phs001258

• Single-cell RNA-seq of bronchoalveolar lavage (BAL) fluid of late stage severe COVID-19 patients

  COVID-19-induced ‘acute respiratory distress syndrome’ (ARDS) is associated with prolonged respiratory failure and high mortality, but the mechanistic basis of lung injury remains incompletely understood. Here, we analyzed pulmonary immune responses and lung pathology in two cohorts of patients with COVID-19 ARDS using functional single cell genomics, immunohistology and electron microscopy. We describe an accumulation of CD163-expressing monocyte-derived macrophages, that acquired a profibrotic transcriptional phenotype during COVID-19 ARDS. Gene set enrichment and computational data integration revealed a significant similarity between COVID-19-associated macrophages and profibrotic macrophage populations identified in idiopathic pulmonary fibrosis. COVID-19 ARDS was associated with clinical, radiographic, histopathological, and ultrastructural hallmarks of pulmonary fibrosis. Exposure of human monocytes to SARS-CoV-2, but not Influenza A virus or viral RNA analogs, was sufficient to induce a similar profibrotic phenotype in vitro. In conclusion, we demonstrate that SARS-CoV-2 triggers profibrotic macrophage responses and pronounced fibroproliferative ARDS.

  Study EGAS00001005634

• Single cell characterization of T-cell lymphoma: RNA (2025-07-31)

  Lymphomas are types of blood cancer derived from lymphocytes, and can be classified into two main categories, Hodgkin's lymphomas (HL) and non-Hodgkin lymphomas (NHL). T-cell lymphoma is a type of NHL that develops from T lymphocytes and accounts for 10-15% of total NHL cases. As a rare disease, T-cell lymphoma is functionally, pathologically, and clinically complex and heterogeneous. The 2016 revision of the WHO classification has listed 29 subtypes of mature T/NK-cell neoplasms, among which over 25 are T lymphocyte in origin. These subtypes of T-cell lymphomas have different biological behaviours and clinical prognosis. Clinically, T-cell lymphoma ranges from indolent (slow-growing) to aggressive (fast-growing and spreading) disease. According to the guideline booklet provided by the Lymphoma Research Foundation (https://lymphoma.org/aboutlymphoma/nhl/), indolent T-cell lymphoma subtypes include adult T-cell leukaemia/lymphoma (ATLL), cutaneous T-cell lymphoma (CTCL), and mycosis fungoides (MF), while the aggressive subtypes include anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma (PTCL), and T lymphoblastic lymphoma (TLBL). PTCL and ALCL represent the most common subtypes of aggressive T-cell lymphoma whereas TLBL is a rare and aggressive subtype mostly diagnosed in children. In this study, we will use single cell RNA sequencing and single cell multiomic methods three aggressive T-cell lymphoma subtypes (ALCL, PTCL and TLBL) and try to gain a deeper insight into the genotypic and phenotypic features of these T-cell lymphomas. . This dataset contains all the data available for this study on 2025-07-31.

  Dataset EGAD00001015669

• Predicting Chemotherapy-Induced Mucositis with Genetic and Clinical Factors

  We hypothesized that genetic variability in the enzymes/proteins involved in drug metabolism, inflammation, and immune function is a major underlying contributor to mucositis incidence and progression and that, based on this variability we can identify variants that influence risk, and develop a mucositis progression prediction model that improves on existing models by incorporating genetic variability along with clinical factors. Using genome wide association study (GWAS) combined with a pathway candidate gene approach and a modified case-control study method, we investigated the hypothesis in a sample of 1092 patients who received a myeloablative dose of melphalan (MEL) followed by autologous hematopoietic stem cell (ASCT) transplantation as treatment for multiple myeloma and for whom banked blood stem cell samples and clinical data were available.

  Study phs000545

• H3Africa - Respiratory Microbiota of African Children

  Shotgun metagenomic sequencing of nasopharyngeal (NP) samples, from children enrolled in a PCV13-vaccinated South African birth cohort was used to explore strain-level pneumococcal colonization patterns and transmission dynamics, and associated antimicrobial-resistance determinants. NP swabs were collected at two-week intervals from birth through the first year of life from 137 infants. Pneumococcal isolates were serotyped and tested for phenotypic antimicrobial resistance. 196 NP samples from a subset of 23 infants were then selected based on changes in serotype or antimicrobial resistance. DNA was extracted directly from the enriched NP samples and shotgun metagenomic sequencing performed. Reads were assembled and aligned against reference pneumococcal genomes. in silico pneumococcal capsular, multilocus sequence typing, and resistome analyses were performed.

  Study EGAS00001004401

• Peripheral blood DNA methylation of Crohn's disease patients starting treatment with adalimumab, vedolizumab or ustekinumab

  In the current study we performed a longitudinal case-control study comparing the peripheral blood DNA methylome of Crohn's disease (CD) patients that were classified as responders and non-responders to adalimumab, vedolizumab, and ustekinumab. Patients with active CD were prospectively recruited and followed up for around 27 weeks into treatment during which response assessment took place. Response was defined as a strict combination of endoscopic- (≥50% reduction in SES-CD score) combined with either corticosteroid-free clinical- (≥3 point drop87 in HBI or HBI ≤4 and no systemic steroids) and/or biochemical response (C-reactive protein (CRP) and fecal calprotectin reduction ≥50% or ≤5 g/mL and fecal calprotectin ≤250 µg/g).

  Study EGAS00001007532

• Exome sequencing of early and late passage Patient Derived Xenogratf Tumoroids with matched Patient Derived Xenogratfs and matched normal liver

  The breadth and depth at which cancer models are interrogated contribute to successful translation of drug discovery efforts to the clinic. In colorectal cancer (CRC), model availability is limited by a dearth of large-scale collections of patient-derived xenografts (PDXs) and paired tumoroids from metastatic disease, the setting where experimental therapies are typically tested. XENTURION is a unique open-science resource that combines a platform of 129 PDX models and a sister platform of 129 matched PDX-derived tumoroids (PDXTs) from patients with metastatic CRC, with accompanying multidimensional molecular and therapeutic characterization. In this specific dataset we focused our attention on early (passage 3) and late (passage 8-12) PDXTs with their matched PDXs and normal liver

  Dataset EGAD50000000266

• 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

• DNA and RNA sequencing data from Ovarian Carcinosarcoma patients from the Glasgow Cohort.

  In this study, we analysed DNA and RNA sequencing data from Ovarian Carcinosarcoma patients, from isolated carcinoma and sarcoma components and investigated DNA variants as well as gene expression. Genomic analyses from this data and further investigation from preclinical models of ovarian carcinosarcoma support the conversion theory for disease development and indicate that microtubule inhibitors could be used to suppress EMT and stimulate anti-tumour immunity.

  Study EGAS00001006605

• Genome Wide Association Study of Subjects with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

  Myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a complex and heterogeneous disease that severely impacts the health and quality of life of those afflicted. Several lines of evidence support the possibility that ME/CFS development may involve a heritable component. In this pilot study, 42 cases that meet the diagnostic criteria of ME/CFS and 38 healthy controls were consented into this study. The goal of this study was to identify candidate polymorphisms that can be used for a large multi-center screening study.

  Study phs001015

• Next Generation Mendelian Genetics: Atypical Werner Syndrome

  Werner syndrome (WS) is an adult-onset progeroid syndrome characterized by accelerated aging. The International Registry of Werner Syndrome in the Department of Pathology, University of Washington, collects WS cases from all over the world. Classical WS is caused by WRN mutations. Those who do not carry WRN are categorized as "atypical Werner syndrome." A small subset of atypical WS is caused by LMNA mutations. There also are many cases whose causes are still unknown. The purpose of this study is to identify other causative gene(s) of atypical WS.

  Study phs000434

• IgM heavy chain V(D)J library sequencing using varied PCR parameters

  When amplifying the rearranged V(D)J genes encoding antigen receptors during adaptive immune receptor repertoire sequencing (AIRR-seq), each cycle of the PCR can produce spurious “chimeric” hybrids of two or more different template sequences. To test the effects of PCR protocol variation on chimera formation in AIRR-seq, we produced IgM heavy chain V(D)J repertoire libraries under 8 conditions, varying the number of PCR cycles, indexing PCR template, input RNA, and extension time. Three donors were sequenced using all 8 conditions.

  Study EGAS50000001037

• Gene expression data of 2D duodenum organoids with or without continuous flow

  We developed a monolayer culture system for small intestinal organoids, and then placed the culture plate on a rotator to generate a constant flow in the overlay medium. This mechanical stimulation facilitated the formation of villus-like structures from the monolayer of small intestinal organoids. We analyzed gene expression of 2D normal duodenum organoids with or without medium rotation. Total RNA was extracted from organoids with or without a four-day medium rotation, and after 0, 1, 2 or 4 days of medium rotation, and sequenced with HiSeq X Ten (Illumina).

  Study JGAS000256

• A transcriptome atlas of human skeletal muscles

  We generated a large transcriptome atlas of human skeletal muscles by collecting biopsies from 6 different muscles to determine molecular signatures that may be distinct between leg muscles. The biopsies were collected from gracilis (GR), semitendinosus (ST), vastus lateralis (VL), vastus medialis (VM), rectus femoris (RF), and gastrocnemius lateralis (GL) muscles. We also investigated molecular differences within the muscle by including two biopsies from the middle and distal sides of the semitendinosus muscle (STM and STD, respectively). In total, 128 samples from 20 individuals (aged 25 ± 3.6 yr) were analyzed.

  Study EGAS00001005904

• WES and RNA-seq of pre-invasive lung adenocarcinoma

  The prevalence of lung adenocarcinoma (LUAD) has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. We performed whole exome-sequencing and RNA-sequencing of samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). This datasets contains the sequencing raw data (FASTQ format).

  Dataset EGAD50000000637

• WGS data of fetal stem cells (15x) and culture-associated mutations of iPSCs and ISC

  This data set includes WGS data of the in vivo acquired mutations in fetal ISCs and HSPCs of 4 foetuses ( T21=2, D21= 2). In addition, this data set includes sub-clonal fetal ISCs to determine the culture-associated mutations of fetal ISCs. Also, it concludes clone +subclone WGS data of iPSCs derived of the fetal ISCs

  Dataset EGAD00001008475

• Deregulation of FOXF1/FENDRR from t(14;16)(q32;q24) defines a subtype of high risk lineage ambiguous leukemia

  Despite great progress in understanding the genomic basis of immature T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL) and acute leukemias of ambiguous lineage (ALAL), there are still cases that lack defining genetic markers, complicating risk stratification and limiting targeted therapeutic options. Here, we describe a subtype of leukemia defined by the t(14;16)(q32;q24) translocation, which places the FOXF1 gene and its antisense long noncoding RNA gene FENDRR under the regulatory control of the BCL11B enhancer, leading to their ectopic transcriptional activation. Analysis of different high-throughput sequencing data, including WGS, RNA-seq, scDNA-seq, scRNA-seq, ChIP-seq, ATAC-seq, and HiChIP-seq, identified BCL11B-enhancer mediated deregulation of FOXF1/FENDRR as a hallmark of a subtype of high-risk lineage ambiguous leukemia that is potentially amenable to targeted therapeutic intervention.

  Study EGAS50000001255

• Profiling molecular heterogeneity in human primary microglia

  In the brain the cells that control inflammation are called a type of white blood cell called microglia. Microglia are located throughout the brain and spinal cord and account for 10–15% of all cells found within the brain. As the resident white blood cells, they are the main active immune defence in the central nervous system (CNS). Microglia are part of an important class of cells known as macrophages that have two main states: M1 and M2. M1 cells are pro- inflammatory, leading to more inflammation, while M2 are anti-inflammatory, and drive wound healing. In this study, we will collect primary microglia from surgical biospies of 100 individuals. 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 EGAD00001005736

• Berlin Neuroblastoma Patient Genomic Data from Targeted Sequencing for Detection of TERT rearrangement breakpoints to monitor neuroblastoma

  Our objective was to establish a liquid biopsy-based monitoring strategy for pediatric high-risk neuroblastomas that are harboring genomic TERT rearrangements at diagnosis. TERT rearrangement breakpoints are detected by a hybrid capture-based neuroblastoma DNA panel sequencing (published in PMID: 34442335) in tumor material and are reflected in cell-free tumor DNA and can serve as robust biomarkers for disease activity. Within the dataset, 5 tumors of 4 pediatric patients with a neuroblastoma were DNA sequenced. Provided are FASTQ data files, bam and bambai files, as well as breakpoint spanning and encompassing read (enspan) bam and bambai files. Sequencing bam data files are aligned to GRCh37.p13 reference genome (processed).

  Dataset EGAD00001011088

• Nasal MicroRNA during Bronchiolitis and Age 6y Asthma: MARC-35 Cohort

  We analyzed data from the 35th Multicenter Airway Research Collaboration (MARC-35) study to examine the relationship between nasal airway microRNAs (miRNAs) and the risk of developing childhood asthma. MARC-35 is a multicenter prospective cohort study which enrolled infants (age Structured interviews of the parents/guardians were performed by site investigators and clinical details were collected via emergency department and hospital inpatient chart reviews. Following the index hospitalization, trained study personnel conducted telephone interviews with parents/legal guardians at six-month intervals. Participants also underwent nasal swab sampling conducted by trained site personnel during the index bronchiolitis hospitalization and during an in-person follow-up examination at about age 6 years. Total RNA was extracted from nasal swab specimens using Trizol LS reagent (ThermoFisher Scientific, Waltham, MA) and the Direct-zol RNA Miniprep Kit (Zymo Research, Irvine, CA). Small RNA-seq was performed using the PerkinElmer NEXTFLEX® small RNA-seq v3 kit with Unique Dual Indexes (PerkinElmer, Waltham, MA) and sequenced on an Illumina NovaSeq6000 sequencer using an S2 50bp PE Flowcell (Illumina, San Diego, CA). Through dbGaP, limited de-identified phenotypic data (e.g., demographics) and RNA-seq FASTQ files will be made available. Among a cohort of infants hospitalized with bronchiolitis, we applied a small RNA sequencing approach and found miRNAs were associated with asthma risk factors, and highly expressed in lung tissue and immune cells (e.g., TH cells, neutrophils). They also played key roles in mechanisms relating to asthma, such as innate immunity, airway remodeling, and IgE regulation.

  Study phs003564

• Genomics Analysis Reveals Molecular Patterns of Tumorigenesis in HPV-Associated and HPV-Independent Sinonasal Squamous Cell Carcinoma

  The goal of this study was to identify molecular mechanisms of tumorigenesis in HPV-associated and HPV-independent sinonasal carcinoma using high-throughput sequencing approaches. Whole genome sequencing was performed for HPV-associated samples and whole exome sequencing for HPV-independent samples. Ultimately, we identified distinct molecular patterns of tumorigenesis between HPV-associated and HPV-independent disease. Data from patients for which informed consent allowed public sharing are included here.

  Study phs003591

• Integration of genomics and metabolomics in acute myeloid leukemia

  Although targeting of cell metabolism is a promising therapeutic strategy in acute myeloid leukemia (AML), metabolic dependencies are largely unexplored. We aimed to classify AML patients based on their metabolic landscape and map connections between metabolic and genomic profiles. The intracellular metabolome distinguished three AML clusters, correlating with distinct genomic profiles: NPM1-mutated(mut), chromatin/spliceosome-mut and TP53-mut/aneuploid AML that were confirmed by biofluid analysis.

  Study EGAS00001005422

• Combination Immune Checkpoint Inhibition in Australian Rare Cancers_WES

  Combination immune checkpoint inhibition (ICI) with anti-CTLA-4 and anti-PD-1 blockade has demonstrated significant clinical activity across tumour types. Rare cancer patients have limited treatment options due to the scarcity of studies of novel treatment options, so they are often offered chemotherapies untested in their disease. ONJ2016-001/CA209-538 is a prospective, multicentre clinical trial of combination ICI (ipilimumab and nivolumab) in patients with advanced rare cancers, including biliary tract, adrenocortical, rare gynaecological and neuroendocrine cancers (https://clinicaltrials.gov/ct2/show/NCT02923934). The primary endpoint is clinical benefit rate (complete response + partial response + stable disease >3 months) by RECIST 1.1. This study involves generation and analysis of pre-treatment formalin fixed paraffin embedded (FFPE) tumour DNA sequencing data, paired with germline DNA sequencing data, to potentially identify genomic biomarkers that may associate with clinical benefit or other clinical efficacy / toxicity metrics.

  Dataset EGAD00001015465

• MP2PRT: Comprehensive Genomic Profiling to Identify Alterations Associated with Relapse for NCI Standard Risk (SR) B-Lineage ALL and NCI High Risk (HR) B-Lineage ALL with Favorable Genetic Features

  The Molecular Profiling to Predict Response to Treatment (MP2PRT) program is part of the NCI's Cancer Moonshot Initiative. The aim of this program is the retrospective characterization and analysis of biospecimens collected from completed NCI-sponsored trials of the National Clinical Trials Network and the NCI Community Oncology Research Program. This study, titled "Comprehensive Genomic Profiling to Identify Alterations Associated with Relapse for NCI Standard Risk (SR) B-Lineage ALL and NCI High Risk (HR) B-Lineage ALL with Favorable Genetic Features," is one of the selected studies under this program. For this study, genomic characterization (WGS 30X, WXS, Total RNAseq) was performed on NCI Standard Risk B-lineage ALL patients who relapse and subsets of NCI High Risk B-lineage ALL patients who relapse as well as two non-relapse control cases for each relapse case. It was hypothesized that the comprehensive characterization of these sample sets will allow the identification of somatic genetic features that will facilitate early intervention to improve cure rates for those enrolled on future trials. Data were generated and genetic subtype was integrated with clinical variables, including age, presenting white blood cell count, sex, race, and levels of minimal residual disease at the end of induction. Additional secondary alterations were identified and included if they occurred in more than 10 patients. The study has been completed and a manuscript has been prepared.

  Study phs002005

• Effective reprogramming of patient-derived M2-polarized glioblastoma-associated microglia/macrophages by treatment with GW2580

  Purpose: Targeting immunosuppressive and pro-tumorigenic glioblastoma-associated macrophages and microglial cells (GAMs) has great potential to improve patient outcomes. Colony stimulating factor-1 receptor (CSF1R) has emerged as a promising target for reprogramming anti-inflammatory M2-like GAMs. However, treatment data on patient-derived, tumor-educated GAMs and their influence on the adaptive immunity are lacking. Experimental Design: CD11b+-GAMs freshly isolated from patient tumors were treated with CSF1R-targeting drugs PLX3397, BLZ945, and GW2580. Phenotypical changes upon treatment were assessed using RNAseq. Changes in GAM activation were confirmed in a complex patient-derived 3D tumor organoid model serving as a tumor avatar. Results: The most effective reprogramming of GAMs was observed upon GW2580 treatment, which led to the downregulation of M2-related markers, IL-6, and IL-10, ERK1/2 and MAPK signaling pathways, while M1-like markers and gene set enrichment indicating activated MHC-II presentation were substantially increased. Moreover, treatment of patient-derived glioblastoma organoids with GW2580 confirmed successful reprogramming.

  Study EGAS00001007466

• Characterizing Immune Profiles in Extrapulmonary Tuberculosis via RNA Sequencing

  This dataset provides insight into the immune response in extrapulmonary tuberculosis (EPTB), using bulk RNA-seq data to analyze different disease severities. Hierarchical clustering identified three distinct levels of severity, revealing disease progression driven by interferon and IL-1β-mediated signaling. Additionally, the dataset helped develop a diagnostic gene expression signature for both EPTB and pulmonary TB.

  Dataset EGAD50000000943

• RRBS DNA methylation analysis of in vitro differentiation from induced pluripotent stem cells to hepatocyte-like cells

  Fastq files of Reduced Representation Bisulfite Sequencing data (HaeIII, covering about 7 million CpGs per sample) of induced pluripotent stem cells (iPSC), definitive endoderm (DE) and hepatocyte-like cells (HLC). The dataset comprises data generated by the in vitro differentiation protocol Cellartis (Takara Bio, "CEL", n = 4).

  Dataset EGAD00001005933

• Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia

  Purpose Genomic alterations of IKZF1 are common and associated with adverse clinical features in B-ALL, but the relationship between the type of IKZF1 alteration, disease subtype and outcome are incompletely understood. Patients and Methods We used transcriptome and genomic sequencing, and SNP microarray data to determine leukemia subtype and genomic alterations for 688 pediatric patients with B-ALL enrolled into St. Jude Total Therapy 15 and 16 studies. Results IKZF1 alterations were identified in 115 (16.7%) patients, commonly in BCR::ABL1 (78%) and CRLF2-rearranged, BCR::ABL1-like B-ALL (70%), and were associated with five-year cumulative incidence of relapse (CIR) of 14.8 ± 3.3% compared to 5.0 ± 0.9% for patients without any IKZF1 alteration (P < 0.0001). IKZF1 deletions of exon 4-7 (P = 0.0002), genomic IKZF1plus with any IKZF1 deletion (P = 0.006) or with focal IKZF1 deletion (P = 0.0007), and unfavorable genomic subtypes (P < 0.005) were independently adversely prognostic. Patients with both IKZF1 exon 4-7 deletion and unfavorable genomic subtype had a significantly increased risk of relapse (HR = 58.3; 95% CI, 11.9 – 285.4, P < 0.0001) whereas IKZF1 sequence mutations were not independently predictive of outcome. Conclusions Genomic IKZF1plus with any IKZF1 deletion, IKZF1 deletion of exon 4-7, and unfavorable subtype confer increased risk of relapse. The combination of unfavorable genomic subtype and IKZF1 deletion of exon 4-7 identified patients at greatest risk of relapse despite MRD-directed therapy. The type of IKZF1 alteration together with subtype are informative for risk stratification and predict response in patients with B-ALL.

  Study EGAS50000000106

• Childhood Cancer Data Initiative (CCDI): Identification and Targeting of Treatment Resistant Progenitor Populations in T-cell Acute Lymphoblastic Leukemia

  Our goal with this study was to identify the mechanisms of treatment resistance in T-cell acute lymphoblastic leukemia (ALL) using single-cell genomics. We profiled 40 T-ALL cases from the Children's Oncology Group AALL0434 clinical trial using CITE-seq/snATAC-seq, capturing a breadth of immunophenotypes, including early T-cell precursor (ETP) and near-ETP/non-ETP subtypes. By integrating analyses of T-ALL cells with the normal T-cell developmental trajectory, the study identified a specific subgroup of leukemia cells resembling bone marrow progenitors (BMP-like cells). These BMP-like cells were associated with treatment failure and poor overall survival in T-ALL patients. Overall, this study reveals comprehensive multiomic signatures for rapidly assessing risk and tailoring targeted treatment for high-risk T-ALL patients.

  Study phs003432

• NHLBI TOPMed: Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE)

  Started in 2007, the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) is one of the largest asthma cohort studies in the United States. Its overarching goal is to elucidate the genetic underpinnings of asthma and asthma medication treatment response. The cohort was recruited from a large health care system serving southeast Michigan and the Detroit metropolitan area, and the participants broadly represent the demographic and socioeconomic diversity of the region. Control participants (i.e., patients without a diagnosis with asthma) were recruited from the same health system and geographic region. By virtue of their health system enrollment, both asthma case and control patients have longitudinal clinical information which was routinely collected as part of their care. Both case and control patients underwent at detailed evaluation at the time of enrollment which included lung function testing and bronchodilator response. The SAPPHIRE cohort is a member of the Asthma Translational Genomics Collaborative (ATGC). The latter was selected for whole genome sequencing in Phase 3 of the National Heart Lung and Blood Institute's TOPMed Program. The SAPPHIRE sample selected for sequencing includes African American and/or Latino individuals with and without asthma.

  Study phs001467

• Hofer et al., A specific subpopulation of cancer-associated fibroblasts promotes resistance to chemotherapy in triple-negative breast cancer by upregulating G0S2 protein

  Chemotherapy is the standard of care for patients with triple-negative breast cancer (TNBC), but the mechanisms of chemoresistance remain poorly understood. Here, we investigated the role of cancer associated fibroblasts (CAFs) in the chemotherapy response of TNBC, by combining in vivo analyses of TNBC patients with ex vivo cancer modeling, using tumor-on-chip (ToC) technology. Transcriptomic analysis revealed that the proportion of a specific CAF population, the extracellular matrix-producing myofibroblasts (ECM-myCAFs), is reduced after chemotherapy in chemo-sensitive, but not in chemo-resistant TNBC patients. In ToC devices, primary ECM-myCAFs promoted TNBC cell survival under Doxorubicin and Paclitaxel treatment. The mechanism of chemoresistance was elucidated by using single-cell RNA sequencing, advanced cell imaging and functional assays: ECM-myCAFs upregulate the G0/G1 switch 2 (G0S2) protein in TNBC cells, via activation of SRC family kinases. Altogether, our work identifies G0S2 as a new player in CAF mediated chemotherapy resistance in TNBC.

  Study EGAS50000000886

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

  Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and multiple organs of which the pathogenesis is poorly understood. Here we studied differentially expressed coding and non-coding genes in relation to SSc pathogenesis with a specific focus on antisense non-coding RNAs. Skin biopsy-derived RNAs from fourteen early SSc patients and six healthy individuals were sequenced with ion-torrent and analysed using DEseq2. Overall, 4901 genes with a fold change &gt;1.5 and a false discovery rate &lt; 5% were detected in patients versus controls. Upregulated genes clustered in immunological, cell adhesion and keratin-related processes. Interestingly, 676 deregulated non-coding genes were detected, 257 of which were classified as antisense genes. Sense genes expressed opposite of these antisense genes were also deregulated in 42% of the observed sense-antisense gene pairs. The majority of the antisense genes had a similar effect sizes in an independent North American dataset with three genes (CTBP1-AS2, OTUD6B-AS1 and AGAP2-AS1) exceeding the study-wide Bonferroni-corrected ρ-value (PBonf&lt;0.0023, Pcombined = 1.1x10-9, 1.4x10-8, 1.7x10-6, respectively). In this study, we highlight that together with coding genes, (antisense) long non-coding RNAs are deregulated in skin tissue of SSc patients suggesting a novel class of genes involved in pathogenesis of SSc.

  Study EGAS00001002751

• A benchmark of DNA methylation deconvolution methods for tumoral fraction estimation using DecoNFlow

  In cancer patients, circulating cell-free DNA (cfDNA) originates from both healthy and cancer cells, and the proportion of tumor-derived cfDNA serves as a surrogate marker of tumor burden. Tumoral cfDNA can be identified using patient-specific mutations or more general tumor-specific DNA methylation patterns that are preserved in cfDNA, enabling non-invasive cancer detection and monitoring. Accurately estimating tumor fractions remains challenging due to the heterogeneous mixture of cfDNA sources in body fluids. Computational DNA methylation deconvolution methods can address this by estimating tumoral fraction with or without reference methylomes. Here, we benchmarked 10 reference-based and 2 reference-free DNAm deconvolution tools and provide the data generated for this benchmarking, consisting of 10 neuroblastoma cell lines and one healthy cfDNA sample (pooled from 15 healthy cfDNA samples), profiled using cfRRBS.

  Study EGAS50000001529

• Cancer Discovery Hub (CDH), National Cancer Center Singapore

  This is a DAC for data deposited into EGA generated by Cancer Discover Hub, NCCS. The use of datasets in this portal is solely for research and academic use only, uses other than the have to be approved by the relevant DAC members.

  Dac EGAC50000000039

• EFFORT occupationally exposed human stool metagenomes (148 samples)

  Metagenomes of stool samples from 54 pig farmers, 24 broiler farmers and 70 slaughter line workers. Note: Access to the data will only be granted for antibiotic resistance studies in accordance with the EFFORT consents issued by the participants.

  Dataset EGAD00001005444

• BLUEPRINT Epigenetic characterization of megakaryocytes and erythroblasts

  Megakaryocytes and erythroblasts derive from the same progenitor cell type but carry out very different functions. In order to understand how the different functional phenotypes arise we have characterised the epigenetic landscape of these cells.

  Dataset EGAD00001001871

• Characterisation of the genetic landscape of cutaneous leiomyoma and leiomyosarcoma - Leiomyoma RNA

  Cutaneous leiomyoma (cLM) and leiomyosarcoma (cLMS) are rare benign and malignant soft tissue neoplasms showing smooth muscle differentiation, respectively, that arise from mesenchymal cells in the dermis and subcutis. Through whole exome sequencing of cLM and cLMS cases, we observed distinct differences between the somatic mutational profile of these tumour types. FH was identified as a driver gene in cLM with genetic alterations of FH occurring via somatic point mutation, somatic copy number loss, biallelic inactivation and germline point mutations. TP53 and RB1 were identified as driver genes in the cLMS cohort, with genetic alterations of TP53 occurring via somatic and germline point mutations, copy number loss and biallelic inactivation. Using RNA-sequencing, we identified recurrent gene fusions, including CRTC1/3-MAML2 in cLMS and a novel MYLK-MAP3K2 fusion. Analysis of the cell types present in the tumour microenvironment revealed a significantly increased presence of macrophages and decreased presence of myeloid dendritic cells in the cLMS cohort relative to the cLM cohort. Additionally, we identified common driver genes between cLMS and LMS from other sites. Thus, we provide the first in-depth profile of the genetic landscape of cLM and cLMS.

  Dataset EGAD00001014788

• Characterisation of the genetic landscape of cutaneous leiomyoma and leiomyosarcoma - Leiomyosarcoma RNA

  Cutaneous leiomyoma (cLM) and leiomyosarcoma (cLMS) are rare benign and malignant soft tissue neoplasms showing smooth muscle differentiation, respectively, that arise from mesenchymal cells in the dermis and subcutis. Through whole exome sequencing of cLM and cLMS cases, we observed distinct differences between the somatic mutational profile of these tumour types. FH was identified as a driver gene in cLM with genetic alterations of FH occurring via somatic point mutation, somatic copy number loss, biallelic inactivation and germline point mutations. TP53 and RB1 were identified as driver genes in the cLMS cohort, with genetic alterations of TP53 occurring via somatic and germline point mutations, copy number loss and biallelic inactivation. Using RNA-sequencing, we identified recurrent gene fusions, including CRTC1/3-MAML2 in cLMS and a novel MYLK-MAP3K2 fusion. Analysis of the cell types present in the tumour microenvironment revealed a significantly increased presence of macrophages and decreased presence of myeloid dendritic cells in the cLMS cohort relative to the cLM cohort. Additionally, we identified common driver genes between cLMS and LMS from other sites. Thus, we provide the first in-depth profile of the genetic landscape of cLM and cLMS.

  Dataset EGAD00001014790

• Characterisation of the genetic landscape of cutaneous leiomyoma and leiomyosarcoma - Leiomyoma WES

  Cutaneous leiomyoma (cLM) and leiomyosarcoma (cLMS) are rare benign and malignant soft tissue neoplasms showing smooth muscle differentiation, respectively, that arise from mesenchymal cells in the dermis and subcutis. Through whole exome sequencing of cLM and cLMS cases, we observed distinct differences between the somatic mutational profile of these tumour types. FH was identified as a driver gene in cLM with genetic alterations of FH occurring via somatic point mutation, somatic copy number loss, biallelic inactivation and germline point mutations. TP53 and RB1 were identified as driver genes in the cLMS cohort, with genetic alterations of TP53 occurring via somatic and germline point mutations, copy number loss and biallelic inactivation. Using RNA-sequencing, we identified recurrent gene fusions, including CRTC1/3-MAML2 in cLMS and a novel MYLK-MAP3K2 fusion. Analysis of the cell types present in the tumour microenvironment revealed a significantly increased presence of macrophages and decreased presence of myeloid dendritic cells in the cLMS cohort relative to the cLM cohort. Additionally, we identified common driver genes between cLMS and LMS from other sites. Thus, we provide the first in-depth profile of the genetic landscape of cLM and cLMS.

  Dataset EGAD00001014787

• Characterisation of the genetic landscape of cutaneous leiomyoma and leiomyosarcoma - Leiomyosarcoma WES

  Cutaneous leiomyoma (cLM) and leiomyosarcoma (cLMS) are rare benign and malignant soft tissue neoplasms showing smooth muscle differentiation, respectively, that arise from mesenchymal cells in the dermis and subcutis. Through whole exome sequencing of cLM and cLMS cases, we observed distinct differences between the somatic mutational profile of these tumour types. FH was identified as a driver gene in cLM with genetic alterations of FH occurring via somatic point mutation, somatic copy number loss, biallelic inactivation and germline point mutations. TP53 and RB1 were identified as driver genes in the cLMS cohort, with genetic alterations of TP53 occurring via somatic and germline point mutations, copy number loss and biallelic inactivation. Using RNA-sequencing, we identified recurrent gene fusions, including CRTC1/3-MAML2 in cLMS and a novel MYLK-MAP3K2 fusion. Analysis of the cell types present in the tumour microenvironment revealed a significantly increased presence of macrophages and decreased presence of myeloid dendritic cells in the cLMS cohort relative to the cLM cohort. Additionally, we identified common driver genes between cLMS and LMS from other sites. Thus, we provide the first in-depth profile of the genetic landscape of cLM and cLMS.

  Dataset EGAD00001014789

• Genome of the Netherlands

  The Genome of the Netherlands (GoNL) Project characterizes DNA sequence variation, common and rare, for SNVs, short insertions and deletions (indels) and larger deletions in 769 individuals of Dutch ancestry selected from five biobanks under the auspices of the Dutch hub of the Biobanking and Biomolecular Research Infrastructure (BBMRI-NL). The samples come from a representative sample of 250 trio-families from all provinces in the Netherlands. The parent-offspring trios include adult individuals ranging in age from 19 to 87 years (mean=53 years; SD=16 years) from birth cohorts 1910-1994. Sequencing was done on blood-derived DNA from uncultured cells and accomplished coverage was 14-15x. Samples where contributed by LifeLines (http://lifelines.nl/lifelines-research/general), The Leiden Longevity Study (http://www.healthy-ageing.nl; http://www.langleven.net), The Netherlands Twin Registry (NTR: http://www.tweelingenregister. org), The Rotterdam studies, (http://www.erasmus-epidemiology.nl/rotterdamstudy) and the Genetic Research in Isolated Populations program (http://www.epib.nl/research/geneticepi/research.html#gip). The sequencing was carried out in collaboration with the Beijing Institute for Genomics (BGI). The analysis was done by a consortium lead by UMCG, LUMC, Erasmus MC, VU university and UMCU, see http://www.nlgenome.nl. Funding for the project was provided by the Netherlands Organization for Scientific Research under award number 184021007, dated July 9, 2009 and made available as a Rainbow Project of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL).

  Study EGAS00001000644

• STAT1 AM RNAseq

  The transcriptome of peripheral blood cells (PBMCs) from control or patients with an activation mutation on the STAT1 gene was analyzed. This analysis aimed to identify the major changes in the circulating immune cells of patients with STAT1 mutation and compare this with the result of the perturbation prediction tool huva (human variation, R).

  Dataset EGAD00001006962