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• Cancer treatment re-shapes the somatic mutational landscape of normal esophagus - wgs

  Ageing epithelial tissues, including the esophagus, are progressively colonized by somatic mutant clones, some carrying mutations linked to cancer. However, whether normal epithelial mutational landscapes that evolve over decades can be altered by short term interventions such as cancer treatment is not known. Here we sequenced normal esophageal epithelium removed from patients after 5-8 weeks of therapy for esophageal cancer. Some patients had no prior treatment (NT), while others had 8 weeks of 5 Fluorouracil (5-FU) containing chemotherapy (FLOT) or 4 weeks of chemotherapy and radiation directed at the tumor (CROSS). Despite the brief duration of therapy, we observed treatment specific differences in the selection of mutant clones. The median size of mutant TP53 and PPM1D clones in the CROSS group was double that in the other groups. Mutants of the tumor suppressor SPOP were selected in CROSS but not FLOT or NT patients. In FLOT patients we found positive selection of activating MTOR mutations, consistent with the hypothesis that these mutants confer 5-FU resistance. Sequencing densely mutated normal epithelia after cancer reveals treatment specific selection of mutations with potential therapeutic impact.

  Dataset EGAD00001011181

• Cancer treatment re-shapes the somatic mutational landscape of normal esophagus - 0.25mm punches targeted

  Ageing epithelial tissues, including the esophagus, are progressively colonized by somatic mutant clones, some carrying mutations linked to cancer. However, whether normal epithelial mutational landscapes that evolve over decades can be altered by short term interventions such as cancer treatment is not known. Here we sequenced normal esophageal epithelium removed from patients after 5-8 weeks of therapy for esophageal cancer. Some patients had no prior treatment (NT), while others had 8 weeks of 5 Fluorouracil (5-FU) containing chemotherapy (FLOT) or 4 weeks of chemotherapy and radiation directed at the tumor (CROSS). Despite the brief duration of therapy, we observed treatment specific differences in the selection of mutant clones. The median size of mutant TP53 and PPM1D clones in the CROSS group was double that in the other groups. Mutants of the tumor suppressor SPOP were selected in CROSS but not FLOT or NT patients. In FLOT patients we found positive selection of activating MTOR mutations, consistent with the hypothesis that these mutants confer 5-FU resistance. Sequencing densely mutated normal epithelia after cancer reveals treatment specific selection of mutations with potential therapeutic impact.

  Dataset EGAD00001011182

• Cancer treatment re-shapes the somatic mutational landscape of normal esophagus - nanoseq

  Ageing epithelial tissues, including the esophagus, are progressively colonized by somatic mutant clones, some carrying mutations linked to cancer. However, whether normal epithelial mutational landscapes that evolve over decades can be altered by short term interventions such as cancer treatment is not known. Here we sequenced normal esophageal epithelium removed from patients after 5-8 weeks of therapy for esophageal cancer. Some patients had no prior treatment (NT), while others had 8 weeks of 5 Fluorouracil (5-FU) containing chemotherapy (FLOT) or 4 weeks of chemotherapy and radiation directed at the tumor (CROSS). Despite the brief duration of therapy, we observed treatment specific differences in the selection of mutant clones. The median size of mutant TP53 and PPM1D clones in the CROSS group was double that in the other groups. Mutants of the tumor suppressor SPOP were selected in CROSS but not FLOT or NT patients. In FLOT patients we found positive selection of activating MTOR mutations, consistent with the hypothesis that these mutants confer 5-FU resistance. Sequencing densely mutated normal epithelia after cancer reveals treatment specific selection of mutations with potential therapeutic impact.

  Dataset EGAD00001011183

• Cancer treatment re-shapes the somatic mutational landscape of normal esophagus - 2mm targeted

  Ageing epithelial tissues, including the esophagus, are progressively colonized by somatic mutant clones, some carrying mutations linked to cancer. However, whether normal epithelial mutational landscapes that evolve over decades can be altered by short term interventions such as cancer treatment is not known. Here we sequenced normal esophageal epithelium removed from patients after 5-8 weeks of therapy for esophageal cancer. Some patients had no prior treatment (NT), while others had 8 weeks of 5 Fluorouracil (5-FU) containing chemotherapy (FLOT) or 4 weeks of chemotherapy and radiation directed at the tumor (CROSS). Despite the brief duration of therapy, we observed treatment specific differences in the selection of mutant clones. The median size of mutant TP53 and PPM1D clones in the CROSS group was double that in the other groups. Mutants of the tumor suppressor SPOP were selected in CROSS but not FLOT or NT patients. In FLOT patients we found positive selection of activating MTOR mutations, consistent with the hypothesis that these mutants confer 5-FU resistance. Sequencing densely mutated normal epithelia after cancer reveals treatment specific selection of mutations with potential therapeutic impact.

  Dataset EGAD00001011184

• A genotype-phenotype study of tumors from patients with inherited mutations in DNA repair genes

  This study investigated the genomic landscape of tumors from patients with inherited mutations in DNA repair genes. The aim of this study was to determine the relationship between locus-specific loss of heterozygosity (LOH) and genomic signatures of homologous recombination-based DNA repair (HR) deficiency in tumors associated with pathogenic germline variants in DNA repair genes. Cohorts of pathogenic germline variant (PGV) carriers with different cancer types were identified via a cancer genetics registry and clinical practice at Penn Medicine and through our collaborator network. Tumors were analyzed with next generation sequencing (whole exome and/or targeted panel sequencing) with or without transcriptomic analyses. Sub-study #1 "Non-breast/ovarian tumors in germline BRCA1/2 carriers". This study investigated primary non-breast/ovarian tumors that arise in individuals with BRCA1/BRCA2 pathogenic germline variants (PGVs). Whole exome sequencing (WES) using Agilent All-Exon Kit v7 hybrid capture probes was performed on matched tumor and blood germline normal DNA on an Illumina HiSeq. Individual WES data from DNA samples from tumor and normal are available. Sub-study #2: "Breast tumors in germline CHEK2 carriers". This study investigated primary breast tumors that arise in individuals with CHEK2 pathogenic germline variants (PGVs). Whole exome sequencing (WES) using Agilent All-Exon Kit v7 hybrid capture probes was performed on matched tumor and blood germline normal DNA on an Illumina HiSeq. Whole transcriptome RNAseq was performed on tumors. Individual WES data from DNA samples from tumor and normal and RNAseq data from tumor are available. Sub-study #3: "Breast tumors in germline TP53 carriers". This study investigated primary breast tumors that arise in individuals with TP53 pathogenic germline variants (PGVs). Whole genome sequencing (WGS) and/or custom panel targeted sequencing was performed on matched tumor and blood germline normal DNA on an Illumina HiSeq. Whole transcriptome RNAseq was performed on tumors and normal breast tissue. Individual WGS or targeted data from DNA samples from tumor and normal and RNASeq data from tumor and normal are available. Sub-study #4: "Prostate tumors in germline DNA repair carriers". This study investigated prostate tumors that arise in individuals with a variety of pathogenic germline variants (PGVs). Whole genome sequencing (WGS) and/or custom panel targeted sequencing was performed on matched tumor and blood germline normal DNA on an Illumina HiSeq. Whole transcriptome RNAseq was performed on tumors and normal prostate tissue. Individual WGS or targeted data from DNA samples from tumor and normal and RNASeq data from tumor and normal are available.

  Study phs003348

• Nanopore sequencing from liquid biopsy: analysis of copy number variations from cell-free DNA of lung cancer patients

  Molecular cancer paper (https://doi.org/10.1186/s12943-021-01327-5): This dataset contain shallow whole-genome sequencing (sWGS) of plasma cell-free DNA from cancer patients and healthy subjects, obtained with both Nanopore and Illumina technology. A total of 6 cancer patients and 5 healthy subjects have been sequenced with Nanopore; 4 of the cancer patients have been also sequenced with Illumina. In addition, genomic DNA from white blood cells of one healthy subjects, genomic and 160bp DNA from HEK cells have been sequenced with Nanopore. Genome Biology paper: 3 additional healthy samples have been sequenced (HU), two different bioinformatic pipeline were applied. 2019: Fastqs from the molecular cancer paper were re-demultiplexed and adapter-trimmed (using guppy for multiplex samples, and porechop for singleplex) preserving 5' ends to allow fragmentomics analysis. HAC: All the samples were basecalled with the same updated High Accuracy model (the latest at the time of the analysis) and post-processed as the 2019 dataset. Raw FAST5 are currently available upon request, but will be uploaded soon.

  Dataset EGAD00001006888

• MutWP5: CRUK Mutographs of Cancer: Breast: Reduction Mammoplasty (Exome)

  Sequencing of LCM-derived microbiopsies from 10 women who underwent reduction mammoplasty. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Exome data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequently be sent for whole-genome sequencing. Results from this portion of the study will be compared to women who are BRCA1/2 germline carriers and those with cancer. . This dataset contains all the data available for this study on 2023-03-08.

  Dataset EGAD00001010110

• MutWP5: CRUK Mutographs of Cancer: Breast: Reduction Mammoplasty (WG)(Novaseq)

  Sequencing of LCM-derived microbiopsies from 10 women who underwent reduction mammoplasty. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Exome data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequenctly be sent for whole-genome sequencing. Results from this poriton of the study will be compared to women who are BRCA1/2 germline carriers and those with cancer. . This dataset contains all the data available for this study on 2023-03-08.

  Dataset EGAD00001010113

• MutWP5: CRUK Mutographs of Cancer: Breast: Reduction Mammoplasty (Exome)(Novaseq)

  Sequencing of LCM-derived microbiopsies from 10 women who underwent reduction mammoplasty. Goal to assess the mutational burden, spectrum, and clonal dynamics within the tissue. Exome data will be used as a driver and clonality screen, highly clonal or driver-containing samples will subsequenctly be sent for whole-genome sequencing. Results from this poriton of the study will be compared to women who are BRCA1/2 germline carriers and those with cancer. . This dataset contains all the data available for this study on 2023-03-08.

  Dataset EGAD00001010116

• Genome-wide prediction of human embryos

  This dataset includes whole genome sequence information for three individuals (Mother, Father and Newborn) used in this study. Genomes were sequenced using Illumina HiSeq technology. Files included are fastq files in paired read format.

  Dataset EGAD00001002257

• Whole-exome sequencing and microRNA profiling predicted relapse risk of stage I lung adenocarcinomas

  This dataset contains BAM files for RNA-sequencing of stage I lung adenocarcinomas from Asian patients. In total, there are 107 patients and 107 tumor samples.

  Dataset EGAD00001006187

• Collaborative Cohort of Cohorts for COVID-19 Research (C4R): Severe Asthma Research Program (SARP)

  Cohort Description The Severe Asthma Research Program (SARP) has been investigating the clinical, physiologic and molecular phenotypes of asthma since 2000. It is currently following ~400 deeply phenotyped asthma patients. Data Being Submitted Wave 1 questionnaire data includes 397 variables for up to 375 SARP participants in C4R.Wave 2 questionnaire data includes 448 variables for up to 289 SARP participants in C4R.Dried Blood Spot/Serosurvey data includes 7 variables for up to 290 SARP participants in C4R.Derived data includes 43 variables for up to 463 SARP participants in C4R.Phenotype data includes 113 variables for up to 463 SARP participants in C4R.

  Study phs002913

• Collagen XVII Promotes Pancreatic Cancer Through Regulation of PIK3R5

  Pancreatic ductal adenocarcinoma (PDAC) contains a desmoplastic stroma that promotes the aggressive biology of this disease. While the varied mechanisms by which fibrillar collagens contribute to PDAC have been defined, little is known about the contribution of transmembrane collagens. Among this class of collagens, Collagen XVII uniquely contains an extensive intracellular domain that connects intracellular cytoplasmic components with the extracellular matrix. Collagen XVII is best characterized as the defining component of the type I hemidesmosome, an anchoring complex that attaches epithelial cells to the underlying basement membrane. In this study, we characterize the expression of collagen XVII in PDAC and the mechanisms by which it contributes to PDAC biology. We demonstrate that crosstalk between PDAC cells and cancer associated fibroblasts drive collagen XVII expression in vitro and xenograft tumor models in vivo. Genetic depletion of collagen XVII in low-passage patient derived cell lines diminishes their metastatic potential and ability to form tumors in mice. Whole transcriptome sequencing of tumors formed by cells with diminished collagen XVII levels revealed dramatically lower levels of PIK3R5, a regulatory subunit of class IB phosphatidylinositol-3-kinase (PI3K) that interacts with G protein-coupled receptors. Consistent with this, collagen XVII-deficient tumors exhibited lower levels of phosphorylated AKT, a downstream effector of PI3K. The studies highlight the importance of collagen XVII signaling in PDAC and define a novel mechanism by which collagen XVII mediates activation of PI3K.

  Study phs003641

• The spatio-temporal evolution of lymph node spread in early breast cancer

  Purpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localised and systemic disease is key to understanding breast cancer progression, however our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data derive from primary tumours. Experimental design: In 11 treatment-naïve node positive early breast cancer patients without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multi-region sequencing (n=78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumour DNA (ctDNA). Results: Linear evolution from primary to lymph node was rare (1/11) whereas the majority of cases displayed either early divergence between primary and nodes (4/11), or no detectable divergence (6/11) where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 subjects taken peri-operatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients.

  Study EGAS00001002947

• A New CA19-9 Cut-Off Value Identifies Lewis Antigen Status and Refines Prognostic Stratification in PDAC

  This study investigates the clinical utility of serum CA19-9 levels in pancreatic ductal adenocarcinoma (PDAC), with a focus on identifying patients with Lewis antigen–negative status due to germline FUT3 variants. Using data from multicenter prospective cohorts in Taiwan, we analyzed CA19-9 classification, FUT2/FUT3 genotypes, and clinicopathological annotations. The goal of this study is to refine prognostic stratification and reduce false-negative interpretation of CA19-9 in PDAC patients. All participants provided informed consent, and the study was approved by the relevant institutional review boards.

  Study EGAS50000001575

• The effect of freezing delay of cell-type specific transcriptome responses in human brain via snRNA-seq

  In other analysis in the current manuscript, we find a similar gene signature (to dissociation based artifacts in mouse and human tissue) is present in post-mortem microglia and astrocytes, across all snRNA-seq datasets analyzed, although it is highly variable between subjects. ​ Using acutely-resected neurosurgical tissue, we performed single-nucleus RNA-seq and reveal that a similar signature can be detected in microglia following prolonged exposure to room temperature. Tissue handling and methods details, as well as sequencing and analysis details) can be found in the methods section of related manuscript (Marsh et al., 2022). Together, these results suggest that the presence of this signature in post-mortem brain samples may be the result of a combination of acute pre-mortem (agonal state, cause of death, comorbidities, etc.) and post-mortem (post-mortem interval (PMI), storage time, RNA quality, etc.) variables and may not represent normally present cell state.

  Dataset EGAD00001008541

• MGA-NUTM1 fusion in high grade spindle cell sarcoma Data

  There is a total of 4 sample data (2 WGS and 2 RNAseq) belong to 2 patient deposited in this study.

  Dataset EGAD00001004479

• Genomic landscapes of endometrioid and mucinous ovarian cancers and morphologically similar tumor types

  While endometrioid and mucinous ovarian cancers represent nearly a quarter of ovarian cancers, their molecular characteristics and pathologic origins are poorly understood. To characterize the genomic and epigenomic alterations of these ovarian cancer subtypes and evaluate links to morphologically similar tumors from other sites, we performed sequence, copy number, mutation signature, rearrangement, and methylation analyses from tumor samples and matched normal tissues of 133 patients. These analyses included patients with ovarian endometrioid (n=44), ovarian mucinous (n=43), uterine endometrial (n=15), and gastrointestinal mucinous cancers (n=31). In addition to identifying genes previously known to be involved in these tumors, we identified alterations in RAD51C, NOTCH4, SMARCA1/4 and JAK1 in ovarian endometrioid, ESR1 in uterine endometrioid, and SMARCA4 in ovarian mucinous cancers. Whole genome sequencing revealed rearrangements involving PTEN, NF1, and NF2 in ovarian endometrioid tumors, and NF1 and MED1 in ovarian mucinous cancers. The number of alterations and affected genes in ovarian and uterine endometrioid cancers were similar as were genome-wide methylation profiles, suggesting that these tumors may have a similar tissue of origin. By contrast, methylation patterns in ovarian mucinous cancers were more similar to other gastrointestinal mucinous cancers, including mucinous cancers of the stomach, colon, and pancreas. These analyses provide insights into the genomic landscapes and origins of mucinous and endometrioid ovarian carcinomas, providing new avenues for early clinical intervention and management of patients with these cancers.

  Study EGAS50000000523

• Germline variants collaborate with somatic mutations and initiate and/or drive disease in primary myelodysplastic syndrome (MDS) and therapy-related myeloid neoplasms (t-MN)

  Therapy-related myeloid neoplasms (T-MN) are poorly characterized secondary hematological malignancies following chemotherapy/radiotherapy exposure. We compared the clinical and mutational characteristics of T-MN (n=129) and primary myelodysplastic syndrome (P-MDS, n=108) patients. Although the somatic mutation frequency was similar between T-MN and P-MDS patients (93% in both groups), the pattern was distinct. TP53 mutations were more frequent in T-MN (29.5% versus 7%), while spliceosomal complex mutations were more common in P-MDS (56.5% versus 25.6%).In contrast to P-MDS, the ring sideroblasts (RS) phenotype was not associated with better survival in T-MN, most probably due to genetic association with TP53 mutations. SF3B1 was mutated in 96% of P-MDS with ≥15% RS, but in only 32% T-MN. TP53 mutations were detected in 92% T-MN with ≥15% RS and SF3B1 wild-type cases. Interestingly, T-MN and P-MDS patients with “Very low” or “Low” Revised International Prognostic Scoring System (IPSS-R) showed similar biological and clinical characteristics. In a Cox-regression analysis, TP53 mutation was a poor prognostic factor in T-MN, independent of IPSS-R cytogenetic, disease-modifying therapy and NRAS mutation.Our data have direct implications for T-MN management and provide evidence that, in addition to conventional disease parameters, mutational analysis should be incorporated in T-MN risk stratification.

  Study EGAS00001003547

• Swarm Learning to identify COVID-19, tuberculosis and leukemia patients based on blood transcriptomes

  Identification of patients with life-threatening diseases including leukemias or infections such as tuberculosis or COVID-19 is an important goal of modern precision medicine. However, there is an increasing divide between what is technically possible and what is allowed because of privacy legislation. We have recently illustrated that classical machine learning can identify leukemia patients based on their blood transcriptomes. To facilitate integration of any omics data from any data owner world-wide without violating privacy laws, we here introduce Swarm Learning (SL), a decentralized machine learning approach uniting edge computing, artificial intelligence (AI), blockchain and privacy protection without the need for a central coordinator thereby going beyond federated learning. To illustrate its feasibility, using more than 12,000 transcriptomes from peripheral blood mononuclear cells and more than 2,000 peripheral blood transcriptomes we demonstrate that SL of omics data distributed across different individual sites leads to disease classifiers that outperform those developed at individual sites. Yet, SL completely protects local privacy regulations by design. We propose this approach to noticeably accelerate the introduction of precision medicine.

  Dataset EGAD00001006231

• Systematic Growth Factor Profiling Platform for 3D Tumor Models Reveals EstradiolResponsive Cellular Mechanisms of Immunotherapy Resistance

  Epithelial ovarian cancer (EOC) exhibits significant molecular heterogeneity, which is thought to be influenced by the tumor microenvironment (TME). However, the specific factors driving this heterogeneity remain poorly understood. In this study, we integrated growth factoromics and genomic data to identify TME factors contributing to EOC heterogeneity and immunosuppression. Our analysis revealed distinct subgroups of EOC samples with differential responsiveness to specific growth factors, particularly estradiol and R-spondin. Notably, samples with high responsiveness to estradiol and Wnt (C1 cluster) were enriched in the Mesenchymal (MES) molecular subtype, while samples with high responsiveness to R-spondin (C2 cluster) were associated with the Differentiated (DIF) and Immunoreactive (IMR) subtypes. We discovered that the G protein-coupled estrogen receptor (GPER), rather than the classical estrogen receptor alpha (ERα), was the key mediator of estrogen responsiveness and a determinant of molecular subtype classification. Single-cell sequencing analysis identified subsets of estrogen-responsive malignant cell (MAL.PDCD5) and cancer-associated fibroblast (FB.TNFSF10), which were associated with immunosuppressive patterns in the TCGA cohort. Importantly, the interaction between these cell populations significantly increased upon estrogen treatment, suggesting a potential mechanism by which estrogen signaling may contribute to the development of an immunosuppressive TME. Our findings highlight the critical role of estrogen signaling in shaping the molecular heterogeneity and immunosuppressive TME of EOC and provide novel insights into potential therapeutic targets for overcoming immunosuppression in this malignancy.

  Study EGAS50000000422

• A Single-Cell and Spatial Atlas of Early Human Olfactory Development

  The human nasal region is a complex structure derived from neural crest and placodal lineages, but its development remains poorly understood due to limited fetal tissue access and its intricate architecture. To address this, we created a single-nucleus and spatial transcriptomic atlas of the human fetal nasal region using tissue from 10 fetuses between 7 and 12 post-conceptional weeks. Single-nucleus RNA sequencing (snRNA-seq) revealed 34 distinct cell types, including epithelial, cartilaginous, immune, neuronal, glial, muscular, and vascular cells. By integrating snRNA-seq with multiplexed error-robust fluorescence in situ hybridization (MERFISH), we tracked dynamic changes in cell composition and gene expression over time in the olfactory epithelium (OE) and surrounding nasal regions. We identified novel markers of olfactory sensory neuron development and key pathways regulating epithelial patterning and OE morphogenesis. Notably, we observed early molecular signatures consistent with the "one neuron-one receptor" model, with spatially organized expression of 171 olfactory receptor genes. Together, this study presents the first integrated molecular and spatial framework of early human nasal development. It offers an unprecedented molecular blueprint of olfactory system formation and serves as a foundational resource for embryologists and developmental biologists studying sensory neurogenesis, epithelial patterning, and congenital disorders.

  Dataset EGAD50000001712

• Comprehensive genomic analysis for AYA with acute lymphoblastic leukemia

  AYA with B-ALL showed extremely inferior outcomes when compared to children. Genetic basis undelying AYA B-ALL is largely unknown. We performed integrated analysis of RNA-seq (hum0045���JGAS000047) and target DNA-seq.

  Study JGAS000276

• Pre-Existing Skin-Resident CD8 and γδ T Cell Circuits Mediate Immune Response in Merkel Cell Carcinoma and Predict Immunotherapy Efficacy

  Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ~50% response rate to immunotherapy. Here, we attempted to identify novel predictive biomarkers of response through extensive and deep multi-omics interrogation of 186 samples from 116 patients. We collectively integrated bulk RNAseq, single-cell RNAseq, multiplex immunofluorescence, and spatial transcriptomics. Importantly, we were also able to study 14 matched pairs of tissue samples from pre- and post-immunotherapy. In non-responders, tumors show evidence of increased tumor cell cycling, expression of neuronal stem cell markers, and IL-1α/β. Responders have evidence of increased type I/II interferon signatures and evidence of pre-existing tissue resident (Trm) CD8 or Vδ1 γδ T cells that functionally converge with overlapping antigen-specific transcriptional programs and clonal expansion of multiple T cell receptors. Spatial transcriptomics demonstrated higher co-localization of T cells with B and dendritic cells in responders, with evidence of expression of chemokines important for co-stimulation. Finally, immunotherapy increased clonal expansion or recruitment of Trm and Vδ1 cells in tumors in responders, further underscoring their therapeutic importance. These data identify potential novel actionable biomarkers and therapeutic targets for MCC.

  Study phs003629

• Patient-derived pediatric brain tumor organoids faithfully recapitulate primary tumors

  Extensive molecular analysis by many groups has revealed a heterogeneous landscape of embryonal brain tumors, including medulloblastoma (MB) and atypical teratoid/rhabdoid tumor (ATRT). MB, the most common malignant pediatric brain tumor, is comprised of four molecularly distinct subgroups: Wingless (WNT), Sonic Hedgehog (SHH), Group 3 (G3), and Group 4 (G4). Among these, MB-SHH harboring MYCN amplification and TP53 mutation and MB-G3 with MYC overexpression or amplification constitute the most aggressive tumors, have the poorest clinical outcomes, and lack effective therapeutic options for recurrent disease. Here we describe the establishment of tumor organoid (TO) models from patient-derived orthotopic xenografts (PDOX) of MYCN-amplified and TP53-mutant MB-SHH, MYC-amplified MB-G3 and two ATRT which all grew in mice when reimplanted into the cortices of naïve recipient animals (TOX). Methylation, bulk and single-cell RNA sequencing, and whole genome sequencing demonstrated that TOs and TOXs faithfully recapitulated the molecular landscape and heterogeneity of PDOXs and primary patient tumors compared to established cell lines. The development of TOs will facilitate in vitro high-throughput drug or CRISPR screens without the need for use tumor-bearing mice. This will also accelerate the identification and validation of new vulnerabilities and in vivo preclinical testing toward clinical trials.

  Study EGAS00001008305

• Multi-omic dataset utilized in the analysis of a phase II study of epigenetic priming followed by nivolumab in lung cancer

  This dataset includes sequence files from whole exome sequencing and bulk RNA sequencing of tissue and blood biospecimens from a phase II clinical trial investigating epigenetic priming followed by immune checkpoint blockade in non-small cell lung cancer (NSCLC; NCT01928576). There are 78 whole exome sequencing files and 36 bulk RNA sequencing files included in this dataset.

  Dataset EGAD50000001336

• pan-cancer plasma cfRNA

  Dataset contains mRNA capture sequencing data from plasma of 266 different human donors. The first, pan-cancer, cohort covers 25 high-grade to metastatic cancer types (8 cancer patients per type) and a control group (8 healthy donors). The validation cohort comprises additional plasma samples from ovarian, prostate and uterine cancer patients (12 per type) as well as additional samples from controls (22 new and 8 repeated). Samples were sequenced on a NovaSeq 6000 and are provided in FASTQ format.

  Dataset EGAD00001009713

• Multi-omics Profiling of Airway Neutrophils and Microbiome in Stable Bronchiectasis

  This dataset comprises raw sequencing data generated from a multi-omics study investigating airway neutrophils and the microbiome in patients with stable bronchiectasis. Samples consist of multiplexed pools derived from blood and sputum collected from multiple subjects. Each pool represents a combination of biological materials from different individuals, and therefore individual-level metadata such as sex and disease stage are not attributable at the sample level. The dataset aims to characterize immune and microbial profiles associated with chronic airway inflammation in bronchiectasis.

  Dataset EGAD50000002607

• Correlates of Human Nerve Repair

  This is a longitudinal prospective cohort study in patients with carpal tunnel syndrome undergoing decompression surgery. Phenotypic data and skin biopsies were collected before and 6 months after surgery to determine molecular and cellular correlates associated with neural regeneration and neuropathic pain. RNA sequencing was performed in the skin samples and differential gene expression was determined post compared to pre surgery. The molecular changes identified in skin were correlated with the clinical phenotype representing neural regeneration.

  Study phs001796

• WGS and WES of 78 pairs Chinese gastric cancer

  Gastric Cancer (GC) is a highly heterogeneous disease. To identify potential clinically actionable therapeutic targets that may inform individualized treatment strategies, we performed whole-exome sequencing on 78 GCs of differing histologies and anatomic locations, as well as whole-genome sequencing on two GC cases, each with 3 primary tumours and 2 matching lymph node metastases. The data showed two distinct GC subtypes with either high-clonality (HiC) or low-clonality (LoC).

  Study EGAS00001001056

• Susceptibility_genes_for_the_development_of_SLE_during_treatment_of_IBD

  A potential and very serious side effect of treating IBD with antiTNFa therapies (the currentgold standard) is the development of systemic lupus erythematosis (SLE). This side effect israre and unpredictable. Out of several thousand cases having received treatment, theUniversity of Calgary have accumulated 12 individuals with full phenotyping and novelserological antibody discovery panel data. We propose to exome sequence these samples inan effort to identify rare highly-penetrant variants that could be underlying this severephenotype.

  Study EGAS00001000387

• UROMOL 2020 - RNA-seq data

  The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters.

  Study EGAS00001004693

• 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).

  Study EGAS00001000066

• Detection of clinically relevant genetic and transcriptomic landscape in DLBCL uniformly treated by R-CHOP

  Recent studies using next-generation sequencing strategies have described the landscape of genetic alterations in diffuse large B-cell lymphoma (DLBCL). However, little is known about the clinical relevance of recurrent mutations and copy number alterations and their transcriptional footprints. This study examines the frequency, interaction and clinical impact of recurrent genetic aberrations in DLBCL using high-resolution technologies in a large population-based cohort.

  Study EGAS00001002657

• SOFT_study___sequencing_premenopausal_breast_cancer

  Our project will examine the role of PIK3CA mutations and their sensitivity to endocrine therapies and its role, with the addition of complete ovarian suppression. We plan to test our hypotheses using tumour samples collected from patients enrolled in the SOFT/IBCSG24-02 clinical study (Suppression of Ovarian Function Trial – (NCT00066690). SOFT is a phase III trial that randomised 3066 premenopausal women to evaluate if adding ovarian suppression to adjuvant endocrine therapy will improve clinical outcomes.

  Study EGAS00001000983

• Whole genome sequencing of ASD quartet families

  Autism spectrum disorder (ASD) is genetically heterogeneous with >100 susceptibility genes known. We used whole-genome sequencing (WGS) of 85 quartet families (two parents and two ASD-affected siblings) to comprehensively examine mutation characteristics. Our results emphasize using WGS to maximize the detection of all classes of mutations potentially involved in autism, and to enable the interpretation of that data in confirmatory and predictive diagnosis in different individuals in a family.

  Study EGAS00001001023

• Breast Cancer - immune clusters - RNA-seq

  In this study we use expression data from breast cancer tumors to define immune clusters in breast cancer. Immune clusters have gradual levels of immune infiltration. In the intermediate immune infiltration cluster, we found a worse prognosis which is independent of known clinicopathological features. We also found the immune clusters associated with treatment response. Further using gene expression data and deconvolution algorithms to dissect the immune contexture of the clusters.

  Study EGAS00001003631

• Genetic subclone heterogeneity of tumor-initiating cells in human colorectal cancer

  A subset of tumor-initiating cells (TIC) drives colorectal cancer (CRC) progression in serial mouse xenografts. The TIC compartment itself is heterogeneous and comprises hierarchically organized long-term TIC, tumor transient amplifying cells, and delayed contributing TIC. To address the genomic heterogeneity of the CRC TIC compartment, genome-wide high-coverage whole genome sequencing was performed on patient tumors (n=3), corresponding serially passaged TIC-enriched spheres, and serial xenografts.HIPO P002

  Study EGAS00001001857

• Single-cell RNA sequencing of 6 follicular lymphoma tumors

  Follicular lymphoma (FL) is an indolent cancer of mature B-cells but carries increased risk of transformation to a more aggressive histology over time. We present here comprehensive profiling both tumor and immune compartments in 6 diagnostic FL biopsies by single-cell RNA sequencing. This confirmed results from 155 FL tumors characterized by mass cytometry (CyTOF) which revealed two distinct evolutionary trajectories with disparate risk of transformation and alternate biologies.

  Study EGAS00001005257

• Dual-mTOR inhibitor Rapalink-1 reduces prostate cancer patient-derived xenograft growth and alters tumor heterogeneity

  Bone metastasis is the leading cause of prostate cancer (PCa) mortality, frequently marking the progression to castration-resistant PCa. In this study, we compared the molecular pathways enriched in a set of bone metastasis from breast and prostate cancer from snap-frozen tissue. To further model PCa drug resistance mechanisms, we used two patient-derived xenografts (PDX) models of bone-metastatic PCa, BM18 and LAPC9.

  Study EGAS00001004431

• UROMOL 2020 - SNP data

  The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we performed a large integrative multi-omics analysis of patients diagnosed with NMIBC (n=834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters.

  Study EGAS00001004862

• RNA-sequencing of mechanical stress induced osteoarthritis-like damage in aged human cartilage explants treated with the anti-deiodinase iopanoic acid

  The current study aimed to confirm chondroprotective effects of the D2 inhibitor iopanoic acid (IOP) in an ex vivo aged human osteochondral explant model in which injurious mechanical stress is applied to inflict OA-like damage. This dataset contains RNA-seq (Illumina HiSeq X ten) of osteochondral explant cartilage from aged human patients that underwent a joint replacement surgery due to OA (N=10 donors; n=21 explants).

  Study EGAS00001006242

• Mapping genetic effects on cell type-specific chromatin accessibility using single nucleus ATAC-seq

  Gene regulation is highly cell type-specific and understanding the function of non-coding genetic variants associated with complex traits requires molecular phenotyping at cell type resolution. In this study we performed single nucleus ATAC-seq (snATAC-seq) and genotyping in peripheral blood mononuclear cells from 13 individuals. We mapped chromatin accessibility QTLs (caQTLs) in each immune cell type and sub-type in a subset of 10 samples of European genetic ancestry.

  Study EGAS00001006184

• Pre-diagnostic saliva microbiota of Finnish children with autoimmune diseases

  Pre-diagnostic saliva microbiota samples of Finnish children (aged 11/12 years). This is a case-control study, where case refers to the children who developed Type 1 DM or IBD later in life and control refers to the children who were free from these diseases. The aim of the study was to find biomarkers in saliva microbiota that may help us predict DM or IBD before the onset of these diseases.

  Study EGAS00001006949

• GWAS on covid-19 severity and susceptibility in the province of Bergamo, Italy

  This is a case-control GWAS that involved the voluntary recruitment of inhabitants of the Bergamo province via an online questionnaire. We collected detailed clinical data and verified all information through personal interviews. Cases (severe COVID-19; G1) and controls (mild or asymptomatic COVID-19, G2; non-infected, G3) were matched by age, sex and risk factors

  Study EGAS00001007310

• The cellular state space of AML unveils novel NPM1 subtypes with distinct clinical outcomes and immune evasion properties

  Acute myeloid leukemia (AML) is a genetically and cellularly heterogeneous disease. We characterized 120 AMLs using bulk genomic and transcriptomic analyses (WES, MP-WGS, RNA-seq), and single-cell RNA sequencing (scRNA-seq). Our results reveal an extensive cellular heterogeneity that distorts the bulk transcriptomic profiles. Notably, NPM1 mutated AML could be stratified into two novel, clinically relevant classes (NPM1class I and NPM1class II).

  Study EGAS50000001084

• Oral microbiome metagenomic sequencing - Human Phenotype Project (HPP)

  This study characterizes the oral microbiome of participants enrolled in the Weizmann Institute Human Phenotype Project (HPP), a longitudinal cohort study. Oral swab samples were collected and subjected to shallow whole-genome sequencing using the Gencove low-pass sequencing platform. Raw reads include residual human host sequences in addition to microbial sequences. The dataset comprises metagenomic FASTQ files from [N] participants. Data access is restricted in accordance with participant informed consent and Weizmann IRB approval

  Study EGAS50000001763

• USZ Dermatology and UZH DQBM DAC

  This DAC is responsible for datasets arising from the collaboration between USZ Department of Dermatology and UZH Department of Quantitative Biomedicine.

  Dac EGAC50000000853

• 3.5KJPNv2, an allele frequency panel of 3,552 Japanese individuals

  In the Tohoku Medical Megabank Project, we have conducted whole-genome sequencing of nearly 4,000 individuals from a Japanese population, and constructed an allele frequency panel of 3,552 individuals (3.5KJPNv2) after removing genetically related individuals. The 3.5KJPNv2 was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. The 3.5KJPNv2 includes variants in chromosome X and mitochondrial genome as well as autosome. The submitter has changed the access level of this study from controlled-access [Type I] to un-restricted access since 11th, January, 2019. The un-restricted access data ?hum0015.v3.3.5kjpnv2.v1? are available at the NBDC site: https://humandbs.biosciencedbc.jp/en/hum0015-v3. This study does not contain any controlled-access dataset.

  Study JGAS000159

• RNA-seq FASTQ files from newborn screening dried blood spot samples

  Paired-end RNA-seq FASTQ files from 21 newborn screening dried blood spot (DBS) samples. These DBS samples were obtained from extremely low gestional age newborns, where 10 of them were affected by a fetal inflammatory response (FIR) before birth, and 11 were unaffected. Total RNA was sequenced using an Illumina NextSeq-500 instrument. The sample preparation protocol included the depletion of rRNA and globin mRNA using the Globin Zero Gold rRNA Removal Kit from Illumina. Libraries were prepared using the NebNext Ultra TM II Directionl RNA LIbrary Prep Kit (New England Biolabs). Each sample was sequenced in 4 lanes, leading to 8 FASTQ files per sample and a total of 21x8=168 FASTQ files. There is an additional number of 8 FASTQ files corresponding to sample BS13, which was downsampled to 1/4 of its original depth (see BS13_README file for details).

  Dataset EGAD00001004991

• Genomic Advances in Sepsis (GAinS) genotyping

  This cohort comprises a subset of patients enrolled in the Genomic Advances in Sepsis (GAinS) study, an established biobank of adult sepsis patients. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Patients with sepsis due to community acquired pneumonia or faecal peritonitis were recruited from 35 hospitals across the UK from 2005-2018, with samples for functional genomics and detailed clinical information collected over the first five days of ICU admission to investigate how host genetics affects the individual repsonse to sepsis. DNA was extracted from buffy coat or whole blood samples using the Qiagen DNA extraction protocol, the automated Maxwell Blood purification kit (Promega), or the QIAamp Blood Midi kit protocol (Qiagen). Genotyping data were generated using the Illumina HumanOmniExpress BeadChip (295 patients), the Infinium CoreExome BeadChip (655 patients), and the Infinium Global Screening Array BeadChip (307 patients). Genotyping QC and imputation into the Haplotype Reference Consortium was perfomed within each batch. The datasets were combined and following post-imputation filtering data were available on 1168 samples.

  Dataset EGAD00001015369

• 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

• PROP1_study

  The dataset for the PROP1 study consists of samples of patients with combined pituitary hormone deficiency due to two most prevalent mutations in the PROP1 gene (c.301_302delGA and c.150delA) and healthy relatives and controls. All subjects were genotyped for 21 single nucleotide polymorphisms surrounding the PROP1 gene in order to assess the potential ancestral origin of the respective mutations. The genotype data are displayed in the vcf format.

  Dataset EGAD00001001303

• Metagenome for FINRISK2002

  The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012). The files are in FASTQ format.

  Dataset EGAD00001007035

• Whole genome sequence: cardiomyopathy, 1 myotonic dystrophy patient

  In this study, we analyzed the genomic information by whole genome sequencing using peripheral blood samples from patients with various cardiovascular diseases including severe heart failure to identify genetic variants related to the pathology of cardiovascular diseases. The purpose is to elucidate the underlying mechanism and develop new therapeutic interventions for cardiovascular disease.

  Study JGAS000706

• Transcriptome analysis of adolescents and young adults with Acute Lymphoblastic Leukemia

  The primary purpose of the research is identification of novel chromosome translocations in adolescents and young adults (AYA) with Acute Lymphoblastic Leukemia (ALL). We searched for novel chromosome translocations in 99 philadelphia-chromosome negative ALL cases (including 76 AYA cases) by RNA-seq using next-generation sequencers, and have discovered some novel chromosome translocations.

  Study JGAS000047

• ChIP-seq data of H3K4me3, H3K27ac and H3K27me3 on multiple human embryonic tissues.

  The regulatory landscape of the human genome during organogenesis is undescribed for most tissues. We used ChIP-seq to survey histone modifications in 13 human embryonic tissues. We describe patterns of both common and tissue-specific marking of promoter activation and repression and use enhancer usage to infer regulatory pathways.

  Study EGAS00001003163

• Gut metagenome/FR 2002

  The main goal of the project is the study the associations between the gut metagenome and human health. The dataset contains data for n=7211 FINRISK 2002 participants who underwent fecal sampling. Demultiplexed shallow shotgun metagenomic sequences were quality filtered and adapter trimmed using Atropos (Didion et al., 2017), and human filtered using Bowtie2 (Langmead and Salzberg, 2012).

  Study EGAS00001005038

• Influence of age on molecular changes and treatment stratification in multimodal glioblastoma therapy

  Background: The increasing life expectancy has led to a rise in high-grade gliomas, particularly in patients of older age. The impact of chronological age, associated molecular changes and contributing factors on therapy response, progression-free survival (PFS) and overall survival (OS) remain uncertain. Methods: Between January 1st, 2016, and December 31th, 2021, patients with glioblastoma IDH-wt (CNS WHO grade 4) were included. RNA- and T-cell receptor sequencing was performed in a subset of patients. Primary outcome parameters were extent of resection (EOR), progression free- and overall survival. Multivariate analysis was performed to identify independent predictors of survival. Results: A total of 286 patients were included. The mean age was 66.4 years. Chronological age did not correlate with overall survival (r=0.12). With age, tumor immune composition changed towards macrophages with M2 phenotype and decreased numbers of CD8+ and neutrophiles. Aging related genes were not enriched. Beyond 69.5 years of age, despite similar PFS (p=0.0783), OS (p<0.0001) was significantly shorter, compared to younger patients. Extent of resection and adjuvant radiochemotherapy were significant predictors of OS (p<0.0001). No difference in PFS and OS was found between younger and older patients treated with maximal safe resection, followed by concomitant RT and chemotherapy and adjuvant chemotherapy. Conclusions: This study suggests that age alone should not be the sole determinant in therapeutic decision-making for glioblastoma patients. Gross total resection and adjuvant therapy, tailored to individual clinical status, significantly impact survival outcomes. Patient-specific treatment strategies are important to minimize undertreatment and optimize therapeutic outcomes in older patients.

  Study EGAS00001008246

• Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high risk disease

  Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are poorly understood. We performed whole exome sequencing, copy number variation and/or RNA-Seq for 65 patients to discover mutations at diagnosis and blast crisis (BC). Forty-six chronic phase patients with the extremes of outcome were studied at diagnosis. Cancer gene variants were detected in 15/27 patients (56%) with subsequent BC or poor outcome and in 3/19 optimal responders (16%), P=.007. Frequently mutated genes at diagnosis were ASXL1, IKZF1 and RUNX1. The methyltransferase SETD1B was a novel recurrently mutated gene. A novel class of variant associated with the Philadelphia translocation was detected at diagnosis in 11/46 patients (24%) comprising fusions and/or rearrangement of genes on the translocated chromosomes, with evidence of fragmentation, inversion and imperfect sequence reassembly. These were more frequent at diagnosis in patients with poor outcome: 9/27 (33%) versus 2/19 optimal responders (11%), P=.07. Thirty-nine patients were tested at BC and all had cancer gene variants, including ABL1 kinase domain mutations in 58%. However, ABL1 mutations co-occurred with other mutated cancer genes in 89% of cases, and these predated ABL1 mutations in 62% of evaluable patients. Gene fusions not associated with the Philadelphia translocation occurred in 42% of patients at BC and commonly involved fusion partners that were known cancer genes (78%). Genomic analysis revealed numerous relevant variants at diagnosis in patients with poor outcome and all patients at BC. Future refined biomarker testing of specific variants will likely provide prognostic information to facilitate a risk-adapted therapeutic approach.

  Study EGAS00001003071

• Neutrophils infected with Leishmania donovani

  In the context of studying visceral leishmaniasis, neutrophils infected with Leishmania donovani have been compared to uninfected neutrophils. Compared time points are 0, 6 and 24 hours post infection. Neutrophils of three human donors have been used. Overall 6 samples for infected neutrophils at time point 6 hours and 6 samples for infected neutrophils at time point 24 hours exist, including three biological samples and two technical samples. Uninfected neutrophils represent 3 samples at time point 0 hours, 3 samples at time point 6 hours and 3 samples at time point 24 hours. Transcriptome of Leishmania donovani culture has been assessed in two replicates.

  Study EGAS00001004912

• WES on tumor DNA and germline DNA in pediatric cancer

  This dataset contains whole exome sequencing (WES) data (various enrichment methods) from tumor DNA samples of various pediatric cancer entities. Files are provided in fastq format. Samples were sequenced on a Novaseq6000 or Hiseq2500 (Illumina).

  Dataset EGAD00001007816

• Clinical and ctDNA data for IMpassion031

  Clinical and ctDNA data for IMpassion031, including survival, response, and ctDNA data from baseline through post-surgery time points. 222 samples run on Signatera assay. File type is csv.

  Dataset EGAD50000001420

• Cerebrospinal Fluid Analysis of HIV-1 Viral Burden in HIV-1 Infected Subjects: Response to Antiretroviral Therapy

  The purpose of this study is to provide a reference profile of small extracellular RNAs in body fluids. These samples were originally obtained in a study that had a different purpose. The purpose of the original study was to collect information on the changes in cerebrospinal fluid (CSF) related to HIV infection, including the viral burden (amount of virus) and the body responses of the infected individual, such as the number and types of lymphocytes in the CSF. In addition to looking at the number and types of lymphocytes in the CSF, this original study also examined the presence of markers of inflammation and other chemical changes, and the relationship of those changes to nervous system dysfunction in AIDS.

  Study phs001694

• Health Effects of Arsenic Longitudinal Study

  The Health Effects of Arsenic Longitudinal Study (HEALS), a multidisciplinary and large prospective cohort study in Araihazar, Bangladesh, was established to evaluate the effects of full-dose range arsenic (As) exposure on various health outcomes. We applied array-based genotyping technologies to baseline DNA samples from a subset of the HEALS study and linked those genotypes to data on arsenic species measured in urine. We used these data to identify regions influencing arsenic metabolism (AS3MT and FTCD). We also applied array-based DNA methylation technologies to baseline DNA samples from a subset of individuals from HEALS. These data were linked to data on arsenic concentration (in both urine and drinking water) to identify regions of the genome where DNA methylation is impacted by arsenic exposure.

  Study phs003839

• DAC for DRS peripheral blood, University Medical Center Johannes Gutenberg University Mainz

  This DAC is in relation to the DRS samples of peripheral blood of healthy control

  Dac EGAC50000000667

• Cellular and Molecular Characterization of Renal Cell Carcinoma

  We are performing a comprehensive cellular and molecular characterization of renal cell carcinoma. This work includes an initial cohort of patients whose tumors (and adjacent normal tissue) underwent single cell analysis. Single-cell RNA sequencing (scRNA-seq) and TCR sequencing (scTCR-seq) analysis of untreated clear cell renal cell carcinoma tumor and adjacent normal tissue was performed across disease stages. This initial cohort includes 13 patients: 4 with early stage disease (stage I/II), 4 with locally advanced disease (stage III), and 5 with advanced/metastatic disease (stage IV). Whole exome sequencing on tumor and normal tissue was also performed. 

  Study phs002252

• WXS of 147 lung cancer patients treated with immunotherapy

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

  Study EGAS00001003781

• Breast Cancer - Subtype defined by an amplification of the HER2 gene

  Clinically positive HER2 (cHER2+) breast cancers (BC) are defined by the amplification and overexpression of the human epidermal growth factor receptor (HER2/ERBB2) gene on chromosome region 17q12 and represent 15% of all BCs. Although anti-HER2 targeted therapies have improved BC’s natural history, the magnitude of their benefit varies widely between patients and deciphering the genomic heterogeneity of cHER2+ BC may provide a basis to better understand patients’ outcome. As part of the ICGC Breast Cancer Working Group effort, we combined whole genome sequencing and transcriptomic analyses of 64 cHER2+ primary invasive carcinomas.

  Study EGAS00001001431

• Whole exome sequencing on Pediatric MDS patients

  WES was performed on 126 cases (SAMD9/9Lmut: 64/67; GATA2mut 24/35, MDS wildtype 38/471) using SureSelect Human All Exon V6 enrichment (Agilent, cat# 5190-8863). The generated libraries were sequenced on the Illumina Hiseq 2500 with 150bp paired-end reads. FASTQ files were processed using SeqNext platform (JSI medical system, Germany), with gene-based alignment to a virtual panel of 300 genes consisting of genes relevant to bone marrow failure, MDS predisposition, and hematological cancers as per the Pan-Cancer studies with cohorts of >10,000 cancers. The generated BAM files are submitted here.

  Study EGAS00001005432

• NTNU Data Access Committee for “ProstOmics: spatial and bulk multi-omics of prostate cancer” datasets archived in Federated EGA Norway

  The ProstOmics project of NTNU contains spatial and bulk multi-omics datasets of prostate cancer, and access request to these datasets are handled by this Data Access Committee on behalf of NTNU.

  Dac EGAC50000000277

• Dataset SNP tumours

  This dataset contains 30 idat files each from 15 SNP array runs on patient colitis-associated colorectal cancer tumours. All phenotypes are cancer. See Baker et al. 2018 Supplementary Table 2 for patient details of 12 tumours used in the analyses in the publication.

  Dataset EGAD00010001587

• WES and RNA-seq raw sequence data for HIFI project

  WES sequence data from 15 samples, RNA-seq sequence data from 19 samples, all sequence data are raw pair-end sequence data in fastq format, sequenced by Illumina platform.

  Dataset EGAD00001004799

• ESGI - Whole Genome Sequencing of samples from the Cilentogen isolates (2019-08-19)

  Deep whole genome sequencing of sampels from the Cilento isolates. The samples are sequenced using the Illumina HiSeq X Ten system. . This dataset contains all the data available for this study on 2019-08-19.

  Dataset EGAD00001005266

• Chromatin Profiling in Twins (2019-08-21)

  50 lymphoblastoid cell lines of adult female Twins which are part of the MuTHER study, processed with the FAIRE assay in order to generate maps of open chromatin. . This dataset contains all the data available for this study on 2019-08-21.

  Dataset EGAD00001005273

• SF11956 snATAC Seq GBM

  IDHR132H Wildtype GBM. Male, 63 Single Nuclei ATAC seq data from high grade human glioma samples. NovaSeq6000 was used for ATAC seq. The files uploaded are bam files created with grch38 reference.

  Dataset EGAD00001005406

• SF11612 scRNA-Seq Recurrent oligodendroglioma

  Single Cell RNA seq from Recurrent oligodendroglioma sample. Gender Male Age 67. NovaSeq6000 was used for RNA seq. The files uploaded are bam files created with grch38 reference through Cellranger count (10xGenomics.)

  Dataset EGAD00001005411

• SF9259S snRNA-Seq Primary GBM

  Single Nuceli Primary GBM 73 Male. Single Nuclei RNA seq from high grade primary glioma sample. NovaSeq6000 was used for RNA seq. The files uploaded are bam files created with grch38 reference.

  Dataset EGAD00001005428

• GATCI whole exome germline variants

  Exome sequences were aligned to the GRCH38 reference genome. Aligned sequence was analyzed with GATK Haplotype Caller to generate germline variant calls. Variant calls are in VCF format. Details for the call can be found in the VCF header

  Dataset EGAD00001005916

• GATCI whole exome somatic variants (MuTect)

  Exome sequences were aligned to the GRCH38 reference genome. Aligned sequence was analyzed with GATK/MuTect, to generate somatic variant calls. Somatic variant calls are in VCF format. Details for the mutect call can be found in the vcf header.

  Dataset EGAD00001005917

• GATCI whole exome somatic variants (SomaticSniper)

  Exome sequences were aligned to the GRCH38 reference genome. Aligned sequence was analyzed with GATK/SomaticSniper, to generate somatic variant calls. Somatic variant calls are in VCF format. Details for the mutect call can be found in the vcf header.

  Dataset EGAD00001005918

• IsoSeq Subreads bam files (PacBio)

  These are the raw subreads bam files for the pacbio IsoSeq data

  Dataset EGAD00001009514

• miRNA data for aSAH patients with or without subsequent vasospasm

  These files contain the normalized and raw count abundances miRNA for aSAH patients. These abundances were obtained using Next-Generation Sequencing after selection of the miRNA in the RNA biobank. In total, there are 28 VSP- and 28 VSP+ patients for two-time points. Normalized data were obtained by applying size factor and VSN normalizations as described in Pulcrano-Nicolas et al. Stroke 2018. Raw count data corresponding to the raw abundances of miRNA in aSAH patients.

  Dataset EGAD00001004185

• Childhood Cancer Data Initiative (CCDI): Comprehensive Genomic Sequencing of Pediatric Cancer Cases (CMRI/KUCC)

  This study provides paired tumor normal genomic sequencing data from ~ 200 children with cancer, including both solid tumors and leukemias, done by the Children's Mercy Research Institute (CMRI) and University of Kansas Cancer Center (KUCC). These data include whole genome sequencing (generally, ~20x), whole exome sequencing (generally, ~300x), bulk RNA sequencing (generally, ~80 million reads), and single-cell RNA and ATAC sequencing (>50,000 reads/cell). Additional phenotypic, pathologic, and genetic data, gathered clinically for these samples, are also provided.

  Study phs002529

• Spatial multiomic analyses reveal carcinogenic pathways in end-stage renal disease

  Patients with end-stage renal disease (ESRD) are at increased risk for acquired cystic kidney disease (ACKD) and renal tumours, but the molecular basis of such disorders remains elusive. Here, we performed spatial immunogenomic analyses on specimens from 43 patients with ACKD and associated tumours. In this study, we characterized the genomic and transcriptomic features of renal tumours in ESRD. Second, we elucidated the genetic background and microenvironment of cysts in ACKD via comprehensive spatial transcriptomics.

  Study JGAS000855

• Genomic features of renal cell carcinoma developed in end-stage renal disease and dialysis

  Patients with end-stage renal disease (ESRD) or receiving dialysis have 3 ���24-fold higher risk for renal cell carcinoma (RCC). Long-term hemodialysis cause acquired cystic disease (ACD) and RCC.���But its carcinogenic mechanism and genomic features are not so clear. In this study, we analyzed whole genome and transcriptome of 38 RCCs, which were developed in ESRD patients receiving dialysis and characterized their genomic features and associations with their histology and dialysis or end-stage renal diseases.

  Study JGAS000533

• Clonal dynamics of normal hepatocyte expansions in homeostatic human livers and their association with the biliary epithelium

  BAM files containing paired-end mtDNA sequencing data from morphologically normal human liver. CCO-proficient hepatocytes acquired from livers in which clonal CCO-deficient hepatocyte patches had been previously identified. Individual BAM files are named according to their patch, line and sample location, where PT denotes tissue near to the portal triad (PT), central hepatic vein (CV) and midway between these two structures (Mid). "Stroma" control samples were used for identifying germ-line variants. Sequenced on NextSeq 500 platform.

  Study EGAS00001006962

• Multimodal Mapping of the Immune Landscape in Human Pancreatic Cancer

  Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that has rendered it largely refractory to immunotherapy. We used single-cell RNA sequencing on patient tumors and matched blood, and we uncovered a previously unappreciated, complex environment of immune-suppressive cellular interactions. These experiments reveal immune checkpoint expression heterogeneity on individual patient T cells, with corresponding ligands on neoplastic and myeloid cells. TIGIT was upregulated on tumor infiltrating CD8+ T cells and was the only checkpoint receptor consistently expressed by exhausted CD8+ T cells. Clinical annotation of the samples revealed that the exhausted signature is most prominent in patients with advanced stages of disease. Our findings suggest individualized combination therapy, involving anti-TIGIT therapies, may be necessary to extend the benefits of immunotherapy to pancreatic cancer patients.

  Study phs002071

• WGS for fibroblasts colonies

  This dataset contains WGS for fibroblasts colonies obtained from carriers and non-carriers of germline POLD1 L474P. Data for single-cell colonies obtained from immortalized fibroblasts are present for eight out of 16 family members (six carriers and two non-carriers). Sequences obtained for colonies after approximately 40 passages also present for six out of these eight colonies (four carriers and 2 non-carriers). Samples marked with "_F2" and "_F3" represent sequences of single cell-derived colonies and colonies after ~40 passages correspondingly.

  Dataset EGAD00001009283

• Usher patients and USH2A-associated RP patients

  This is a Next Generation Sequencing approach based on whole Usher Syndrome genes sequencing with the aim of diagnosing USH patients and USH2A-associated RP patients

  Dataset EGAD50000000687

• Shifted assembly and function of mSWI/SNF family subcomplexes underlie targetable dependencies in endometriod carcinomas

  The mammalian SWI/SNF (mSWI/SNF) family of chromatin remodelers govern cell type-specific chromatin accessibility and gene expression and assemble as three distinct complexes: canonical BAF (cBAF), Polybromo-associated BAF (PBAF), and non-canonical BAF (ncBAF). ARID1A and ARID1B are paralog subunits that specifically nucleate the assembly of cBAF complexes and are frequently dual deleted in highly aggressive differentiated endometrial carcinomas (DECs). Here, in cellular models and primary human tumors, we find that ARID1A/B-mediated cBAF loss results in increased ncBAF and PBAF biochemical abundance and function genome-wide to maintain the DEC oncogenic signature. Further, treatment of ARID1A/1B-mutant cell lines and PDX models in vivo with a clinical-grade SMARCA4/2 ATPase inhibitor, FHD-286, markedly attenuates cell proliferation and tumor growth, and synergizes with carboplatin-based chemotherapy. Taken together, these findings reveal the oncogenic contributions of shifted of mSWI/SNF family complex abundance and chromatin-level gene regulatory functions and suggest therapeutic utility of mSWI/SNF complex small molecule inhibitors in dedifferentiated endometrial carcinoma and other cBAF-disrupted cancer types.

  Study EGAS50000001004

• 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

• WGS

  A genome-wide approach based on next generation sequencing (NGS) is performed on trios ( Patient+ Father + Mother) with SAID in order to identify known and new gene variants associated with certain forms of the disease. WGSwas performed on frozen PBMCs. DNA was extracted using the QIAamp DNA Blood Midi Kit and quantified with Nanodrop. Sequencing was done on a NovaSeq 6000 with S4 flow cells, targeting 30× coverage.

  Dataset EGAD50000002024

• RNA-sequencing data of post-mortem brain tissue taken from individuals with SCA3 and controls

  Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant inherited ataxia worldwide, caused by a CAG repeat expansion in the Ataxin-3 gene resulting in a polyglutamine (polyQ)-expansion in the corresponding protein. Here we have RNA-sequencing data from the cerebellum of individuals with SCA3 and matched controls.

  Dataset EGAD00001009317

• Multiome_HB

  Hepatoblastoma (HB) cells display strong phenotypic heterogeneity with a major impact on drug response, but the underlying mechanisms are poorly understood. Here, we use a single-cell multi-omic strategy to unravel the molecular determinants of this plasticity. HB display a continuum of single-cell states between hepatocytic (scH), liver progenitor (scLP) and mesenchymal (scM) differentiation poles, with an intermediate scH/LP population bordering scLP and scH areas in spatial transcriptomics. Chromatin accessibility landscapes reveal the gene regulatory networks of each differentiation pole, and the sequence of transcription factor activation underlying cell state transitions. Single-cell mapping of somatic alterations reveals the clonal architecture of each tumor, showing that each genetic subclone displays its own range of cellular plasticity across differentiation poles. The most scLP subclones, overexpressing stem cell and DNA repair genes, proliferate faster after neo-adjuvant chemotherapy. These results highlight how the interplay of clonal evolution and epigenetic plasticity shapes the potential of HB subclones to respond to chemotherapy.

  Study EGAS00001006932

• Development of the prevention and therapy of CRC using patient derived culture tissues.

  Tumor tissues consist of functionally heterogeneous cells including those with high clonogenic potential called cancer stem cells (CSCs) which produce differentiated non-tumorigenic progenies. Transplantation assays have been performed to identify cell surface markers in solid tumors including colorectal cancers, which identified several CSC markers such as CD133 and CD44. In addition to the transplantation, the lineage tracing of genetically labelling cells in animal models of cancer qhas been employed to explore the cellular heterogeneity of tumors by identifying the CSCs and its progenies. This approach is particularly useful to investigate solid tumors, where cellular proliferation and differentiation are controlled by niche factors and cell-cell contact with adjacent cells. Lineage tracing of mouse model of cancer unravel the mode of growth of autochthonous tumor in their native environment. In this study, we used patient derived organoids (PDO) established from surgically resected CRC patients to identify the CSC. Single cell RNA-seq analysis identified potential CRC markers, which may exhibit self-renewal activity and produce progenitors

  Study JGAS000139

• SUM-seq data for Primary T-cells differentiated to helper subtypes

  Briefly, naive CD4+ T cells were isolated from PBMCs obtained from buffy coats from three healthy human donors, and differentiated into Th0, iTreg, Th2, Th1, Th17, and IFN-β-activated subsets. This allowed us to study the differentiation of naive CD4+ T cells into distinct helper subsets under the influence of a specific cytokine environment. Following 5 days of differentiation, T cells were left unstimulated or re-stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin to assess their functional responses. Thus, this SUM-seq experiment consisted of 36 multiplexed conditions (3 donors x 6 stimulations x with/without re-stimulation). Single-cell chromatin accessibility and gene expression data is provided as demultiplexed fastq files.

  Dataset EGAD50000001204

• Single-cell RNA sequencing of human kidney transplant nephrectomies with chronic rejection or non-alloimmune graft injury

  This dataset contains raw single-cell RNA sequencing (scRNA-seq) data for five new kidney allograft nephrectomy samples used to construct the described in the following study: https://www.biorxiv.org/content/10.1101/2022.10.28.514222v2.full. The full description of processing is described in the manuscript. Briefly, samples were digested into a single cell suspension and run according to the 10X Genomics Chromium 5’ single cell kit (v2). Sequencing was performed using an Illumina Novaseq instrument. Samples were designated as TXN2 (EGAN00002519570, mycotic pseudoaneurysm, control dataset), TXN3 (EGAN00002235628, renal vein thrombus, control dataset), TXN5 (EGAN00002519573, chronic transplant rejection), TXN6 (EGAN00002519572, chronic pyelonephritis and renal artery stenosis, non-alloimmune graft injury dataset), TXN7 (EGAN00002519576, recurrent focal segmental glomerulosclerosis, non-alloimmune graft injury dataset).

  Dataset EGAD00001015631

• Prostate Cancer Genome Sequencing Project

  Prostate cancer is a prevalent cause of cancer morbidity and mortality in men. In order to characterize the full range of somatic mutations in protein-coding genes that may drive the growth of prostate cancer, we sequenced the exonic regions of genomic and tumor DNA from over 100 patients with high-risk primary prostate cancer. Using hybrid capture and paired end DNA sequencing, we identified mutations in several novel putative prostate cancer genes. We interrogated copy number changes across tumor genomes using high-density SNP arrays, and identified a molecular subtype of cancer characterized by mutation of the ubiquitin ligase subunit SPOP and copy number loss at specific genomic loci.

  Study phs000447

• North American Brain Expression Consortium (NABEC) Exome Sequencing

  A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation, particularly within the context of human tissues. We describe a set of integrated experiments designed to investigate the effects of common genetic variability on mRNA expression distinct human brain regions. We show that brain tissues may be readily distinguished based on expression profile. We find an abundance of genetic cis regulation mRNA expression. We observe that the largest magnitude effects occur across distinct brain regions. We believe these data, which we have made publicly available, will be useful in understanding the biological effects of genetic variation.

  Study EGAS00001002110