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• Deciphering somatic mosaic structural variation in human blood lineages using single-cell multiomics

  Somatic mosaicism (SM), referring to the presence of somatic mutations in sub-populations of cells within healthy individuals, is associated with an increased risk of a variety of diseases, including cancer. Blood is at particularly high risk of SM, given its rapid turnover and functionally- heterogeneous cell-type composition. While the roles of point mutations and large-scale rearrangements in blood SM have been scrutinised in recent years, the functional impact of mosaic structural variants (mSVs) remains poorly understood. Using haplotype-resolved single-cell multi-omics, we explored the mSV landscape of human hematopoietic stem and progenitor cells (HSPCs).

  Study EGAS00001006567

• DAC for "HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling"

  This is the DAC for the study "HIPSD&R-seq enables scalable genomic copy number and transcriptome profiling" of PD Dr. Aurélie Ernst (a.ernst@dkfz.de) B420, DKFZ.

  Dac EGAC50000000452

• Akershus University Hospital Data Access Committee for Immunoglobulin Heavy-Chain locus in Multiple Sclerosis datasets in FEGA Norway

  This is the Data Access Committee appointed by Akershus University Hospital (AHUS) for datasets from Immunoglobulin Heavy-Chain locus in Multiple Sclerosis studies.

  Dac EGAC50000000659

• Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS)

  Advances in antiretroviral therapies (ART) and patient management have improved survival of people living with HIV (PLWH). However, with exposure to ART and associated side effects and toxicities as well as to the virus itself, PLWH are at an increased risk of several chronic diseases. The Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) research network integrates longitudinal clinical data and treatment management of PLWH and provides research infrastructure to support HIV-associated clinical, social, and behavioral outcomes and comparative effectiveness research using data collected from 8 Centers for AIDS Research clinical sites across United States. For detailed study description, see Kitahata et al. (2008, PMID:18263650).

  Study phs001788

• Targeted analysis of cell-free circulating tumor DNA is suitable for early relapse and actionable target detection in patients with neuroblastoma

  Study EGAS00001006027

• BotSeq sequences1

  This is the first dataset for the Botseq sequencing project

  Dataset EGAD00001002263

• Genetic investigation of 12q-amplified osteosarcomas

  Further investigation and characterisation of 12q-amplified low- and high-grade osteosarcomas with MDM2 and/or CDK4 amplification focusing on SV, copy number and gene fusion analyses. In total, 25 cases (33 samples total due to multi-sampling) were included, with some form of sequencing data available for 27 samples. Mate-pair whole genome sequencing (Illumina) is available for 19 samples, longread whole genome sequencing (PacBio HiFi) on 10 samples and RNA-sequencing (Illumina Truseq) on 21 samples. Data is available as BAM files.

  Dataset EGAD50000000707

• Cohort B spatial transcriptomics sequencing

  Cohort B includes IDH-wild type, EGFR amplified, surgically derived glioblastoma tissue samples from male and female individuals. FFPE tissues for each sample in cohort B were analyzed with the 10X Genomics Visium CytAssist protocol. Processed data is available on the NCBI Gene Expression Omnibus database with accession GSE242352.

  Study EGAS50000000956

• Genomic analysis of high-risk prostate cancer.

  Whole genome sequencing analysis of high risk localised primary prostate cancer samples including metastatic samples was performed across 153 tumour samples with matching germline sequencing (whole blood). Samples were all fresh frozen frozen section confirmed tumour specimens and associated clinical and pathological metadata is available for these specimens.

  Study EGAS00001003088

• Single cell RNA sequencing of human cord Blood CD34 Cells

  We performed single cell RNA sequencing and ATAC e valuation of human umbilical cord blood. To explore the differentiation pathway for human lymphoid lineage, our target cells contain CD34-positive cord blood. That population is evaluated by single cell RNA sequencing and single cell ATAC.

  Study JGAS000528

• The mutational landscape of skin tumours in CYLD cutaneous syndrome determined

  Patients with germline mutations in CYLD can develop hundreds of benign skin tumours called cylindromas. The development of multiple tumours within a single patient at sun-protected and sun-exposed sites, varying tumour histological patterns and grades of malignancy allow for the testing of several genetic hypothesis in relation to cutaneous carcinogenesis. By adopting the unprecedented approach of whole genome sequencing of multiple benign skin tumours within individuals in multigenerational families, we set out to study the impact of mutational diversity on models such as multistep carcinogenesis as well as non-sequential carcinogenesis. Using non-negative matrix factorisation (NMF) to discover mutational signatures, we found distinct mutational signatures in identical benign tumours (N=2 patients; n=11 tumours) at sun exposed and sun protected skin tumours within a mother and her daughter. We found recurrent mutations in epigenetic modifying genes in CCS tumours which are known to have an oncogenic dependency on Wnt signalling. We also demonstrate that cutaneous tumours that metastasize to the lung carry a a UV signature, supporting the origin from the skin. Distinct malignant tumours, such as BCC and malignant spiradenocarcinoma carried unique driver mutations. These findings add new dimensions to the existing paradigms of UV-induced skin cancer and highlight the utility of studying rare disease to gain novel insights into genetic mechanisms of tumour formation.

  Dataset EGAD00001004573

• A Study to Evaluate Denosumab in Young Patients With Primary Breast Cancer (D-Beyond)

  This is a prospective, single arm phase IIa trial in which patients with early breast cancer will receive pre-operatively two doses of denosumab 120mg subcutaneously one week apart (maximum 12 days) followed by surgery. Tumor, normal breast tissue and blood samples will be collected at baseline and at surgery. Post-operative treatment will be at the discretion of the investigator.Primary objective: to determine if a short course of RANKL inhibition with denosumab can induce a decrease in tumor proliferation rates as determined by Ki67 immunohistochemistry (IHC) in newly diagnosed, early stage breast cancer in pre-menopausal women.

  Study EGAS00001003252

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

  By investigating an intergenic haplotype on chr21q22, independently linked to inflammatory bowel disease (IBD), ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis, we discover that the causal gene, ETS2, is a master regulator of inflammatory responses in human macrophages and delineate how the risk haplotype increases ETS2 expression. Using a database of cellular signatures, we identified drugs that could modulate this pathway. To validate the anti-inflammatory activity of one class of small molecules in vitro, we treated TPP macrophages with vehicle control or a selective, non-ATP competitive MEK inhibitor (PD-0325901) at 2 doses (100nM and 500nM) and performed RNA sequencing.

  Study EGAS00001007552

• Origination of Ovarian Cancer is Dependent on Specific Aneuploidy Landscape

  Ovarian high-grade serous carcinoma (HGSC), a highly chromosomally instable malignancy, develops through sequential stages of precursors in fallopian tubes including histologically unremarkable but TP53 mutated clones (p53 signature) and serous tubal intraepithelial carcinoma (STIC). Here, we applied RealSeqS to assess aneuploidy in 127 microdissected tubal regions. We found nearly all p53 signatures lost the entire Chr17 chromosome, offering a “two-hit” mechanism of both TP53 and BRCA1 in BRCA1 germline mutation carriers. Proliferatively active STICs harbor gains of 19q12 (CCNE1), 19q13.2, 8q24 (MYCyc), or 8q arm, while proliferatively dormant STICs show 22q loss. Based on aneuploidy patterns in a training set (n= 67), we developed an algorithm, REAL-FAST, to classify NFTE and STICs into 5 clusters. In an independent validation set (n= 72), REAL-FAST was able to detect STIC/HGSC with high sensitivity and specificity. Taken together, REAL-FAST promises a molecular test for diagnosing HGSC precursor lesions based on specific aneuploidy patterns.

  Study EGAS00001007220

• Clinical outcomes in ctDNA-positive urothelial carcinoma patients treated with adjuvant immunotherapy

  Minimally invasive approaches to detect residual disease after surgery are urgently needed to select patients at highest risk for metastatic relapse for additional therapies. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease (MRD) and relapse,1-3 but its clinical value has yet to be demonstrated in a randomised clinical trial. We evaluated outcomes in post-surgical ctDNA-positive (+) patients in a randomised phase III trial of adjuvant atezolizumab versus observation. IMvigor010 enrolled 809 patients with muscle-invasive urothelial carcinoma and did not meet its primary endpoint of disease-free survival (DFS) in the intent-to-treat population. Within the study, an exploratory planned analysis of prospectively collected plasma was performed, which tested the utility of ctDNA to identify patients who may benefit from adjuvant atezolizumab treatment. ctDNA was measured at the start of therapy (cycle 1 day 1; C1D1) and at week 6 (cycle 3 day 1; C3D1), and 581 patients were evaluable for ctDNA. The prevalence of ctDNA positivity at C1D1 was 37% (n=214), and ctDNA positivity identified patients with poor prognosis (observation arm DFS HR= 6.19 (4.29, 8.91), p<0.0001). Here we show that ctDNA(+) patients had improved DFS and overall survival (OS) with atezolizumab versus observation (DFS HR= 0.56 (0.41-0.77); p=0.0003 and OS HR= 0.58 (0.4-0.86); p=0.0063). No difference in DFS or OS between arms was noted for ctDNA-negative patients. The rate of ctDNA clearance was higher with atezolizumab (18%) versus observation (4%) (p=0.0041). Transcriptomic analysis revealed that tumours from ctDNA(+) patients had higher expression of cell cycle and keratin genes. Within the ctDNA(+) patient population in the atezolizumab arm, non-relapsing patients were further enriched in prominent immune response signatures including PD-L1, IFNG, CXCL9, and high tumour mutational burden, whereas relapse was associated with angiogenesis and fibroblast-transforming growth factor-beta signatures (F-TBRS). TCGA molecular subset analysis revealed increased efficacy of atezolizumab in patients with basal-squamous tumours, consistent with underlying tumour-immune contexture. Together these findings suggest that adjuvant atezolizumab may be associated with improved outcomes compared with observation in this high-risk ctDNA(+) population. These findings, if validated in other settings, would shift approaches to post-operative cancer care.

  Study EGAS00001004997

• Identification of the Global miR-130a Targetome Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML

  In this study, we identified miR-130a as a regulator of HSC self-renewal and differentiation. To characterize gene expression changes following enforced expression of miR-130a OE, we performed RNA-seq in CD34+ cord blood (CB) cells transduced with control and miR-130a OE lentiviruses. To capture miRNA targets in an unbiased, transcriptome-wide manner, we perfomed enhanced CLIPseq procol in 2 replicates of CD34+ CB cells and Kasumi-1 cell line, which represent a model system for t(8;21) AML. We chose this cell line, as we found miR-130a to be highly expressed in this AML subtype where it is critical for maintaining the oncogenic molecular program mediated by AML1-ETO. Chimeric Ago2 eCLIPseq in CD34+ CB cells combined with Mass Spectrometry data analysis identified TBL1XR1 as a principal target of miR-130a. To elucidate gene expression changes associated with TBL1XR1 loss of function, we performed RNA-seq in CD34+CD38- CB cells transduced with control and shRNA targeted against TBL1XR1. To determine the functional significance of high miR-130a expression levels in Kasumi-1 cells on the molecular network controlled by AML1-ETO, we performed CUT&RUN assay and RNA-seq in Kasumi-1 cells following miR-130a knock-down (KD). Collectively, our findings reveal a unique role of miR-130a in regulating normal hematopoietic stem cell self-renewal and how elevated levels of miR-130a in t(8;21) AML contribute to the leukemogenesis of this AML subtype.

  Dataset EGAD00001008412

• Longitudinal sequencing of a recurrent paediatric high grade neuroepithelial tumour

  We have studied a unique case of astroblastoma arising in a 6 year-old girl, with multiple recurrences over a period of 10 years, with the pathognomonic MN1:BEND2 fusion 11 surgical samples from either fresh frozen of paraffin embedded material and 1 blood sample were subjected to Illumina short read whole exome sequencing using Agilent SureSelect whole exome v4. Data is provided as 15 BAM files aligned to hg19 with bwa.

  Dataset EGAD00001004118

• WGS of cell-free DNA derived from plasma of patients with pediatric sarcoma and healthy controls, and lcWGS/RRBS of matched tumor tissue

  This dataset contains: i) 241 deep (median 12x) whole-genome sequencing profiles of 95 patients with Ewing sarcoma, 31 patients with other pediatric sarcomas, and 22 additional profiles from healthy controls. Sequencing was performed on a NovaSeq 6000 instrument using the NovaSeq S4 2x100 bp configuration. In addition, pilot experiments for 18 cfDNA samples were performed using Illumina HiSeq 2000/2500 machines (2x75 bp configuration). Data is provided as .fastq.gz files (2 files, .R1 and .R2, per sample). i) Low coverage whole-genome-sequencing on 43 tumor biopsy samples from patients with Ewing sarcoma with matched cfDNA samples. The samples were sequenced using a NovaSeq 6000 instrument with the NovaSeq S4 1x100 bp configuration. Data are provided as unmapped (raw) .bam files. iii) Reduced-representation bisulfite sequencing data for 38 tumor biopsy samples from patients with Ewing sarcoma with matched cfDNA samples, and 2 control samples. RRBS libraries were sequenced on Illumina HiSeq 2000/2500 machines. Data are provided as unmapped (raw) .bam files.

  Dataset EGAD00001007080

• GATCI_Oncoscan_Data

  This dataset contains files generated from Affymetrix Oncoscan Arrays. For each sample there are two paired cel files containing the raw data from AT and GT channels. Raw data has been transfromed to OSCHP signal files also within this dataset.

  Dataset EGAD00010001579

• Bulk RNA-sequencing data from 9 cHL cell lines

  The dataset contains raw data of 27 bulk RNA-sequencing data from 9 cHL cell lines. Paired-end fastq with polyA capture are available for each cell line.

  Dataset EGAD50000001271

• Khoe-San whole genome sequencing

  High-coverage (>30X) whole genome data (FASTQ) for 25 southern African Khoe-San individuals (from five populations). These are the same individuals as in Schlebusch et al. 2020 (EGAD00001006183), but different data.

  Dataset EGAD50000001559

• GIS-LUNGTCR1-2016_VAL-BAM

  This dataset contains BAM files of targeted Amplicon deep-sequencing data, for validation of the mutations found in WES. There are 16 patients and 95 samples in total, including 16 controls and 79 tumors.

  Dataset EGAD00001001980

• Biallelic HMBS Inactivation Defines a Homogenous Clinico-Molecular Subtype of Hepatocellular Carcinoma

  Acute intermittent porphyria (AIP), caused by heterozygous germline mutations of the heme synthesis pathway enzyme HMBS (hydroxymethylbilane synthase), confers high risk of hepatocellular carcinoma (HCC) development. Yet, the role of HMBS in liver tumorigenesis remains unclear. Here we explore HMBS alterations in a large series of 758 HCC. We identify recurrent bi-allelic HMBS inactivation, both in AIP patients acquiring a second somatic HMBS mutation and in sporadic HCC with two somatic hits. HMBS alterations are enriched in truncative mutations, in particular in splice regions, leading to abnormal transcript structures. Bi-allelic HMBS inactivation results in a massive accumulation of its toxic substrate porphobilinogen and synergizes with CTNNB1 activating mutations, leading to the development of well differentiated tumors with a transcriptomic signature of Wnt/ß-catenin pathway activation and a DNA methylation signature related to ageing. HMBS-inactivated HCC mostly affect females, in absence of fibrosis and classical HCC risk factors. These data identify HMBS as a tumor suppressor gene whose bi-allelic inactivation defines a homogenous clinical and molecular HCC subtype.

  Study EGAS00001005986

• Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19

  In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression. ACEI treatment was associated with dampened COVID-19-related hyperinflammation and with increased cell intrinsic antiviral responses, whereas ARB treatment related to enhanced epithelial-immune cell interactions. Macrophages and neutrophils of patients with hypertension, in particular under ARB treatment, exhibited higher expression of the pro-inflammatory cytokines CCL3 and CCL4 and the chemokine receptor CCR1. Although the limited size of our cohort does not allow us to establish clinical efficacy, our data suggest that the clinical benefits of ACEI treatment in patients with COVID-19 who have hypertension warrant further investigation.

  Study EGAS00001004772

• Structural Expression of BMMF in tissues of colorectal, lung and pancreatic cancer patients

  Chronic inflammation, linked to the presence of bovine milk and meat factors (BMMF) and specific subsets of macrophages, results in oxygen radical synthesis and induction of mutations in DNA of actively replicating cells and replicating single stranded DNA (zur Hausen et al., 2017). Cancers arising from this process have been characterized as indirect carcinogenesis by infectious agents (without persistence of genes of the agent in premalignant or cancers cells). Here we investigate structural properties of pleomorphic vesicles, regularly identified by staining peritumour tissues of colorectal, lung and pancreatic cancer for expression of BMMF Rep. The latter represents a subgroup of BMMF1 proteins involved in replication of small single-stranded circular plasmids of BMMF, but most likely also contributing to pleomorphic vesicular structures found in the periphery of colorectal, lung and pancreatic cancers. Structurally dense regions are demonstrated in preselected areas of colorectal cancer, after staining with monoclonal antibodies against BMMF1 Rep. Similar structures were observed in human embryonic cells (HEK293TT) overexpressing Rep. These data suggest that Rep or Rep isoforms contribute to the structural formation of vesicles.

  Study EGAS00001006744

• Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile

  The Multiple Myeloma Research Foundation (MMRF) CoMMpass (Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile) trial (NCT01454297) is a longitudinal observation study of 1000 newly diagnosed myeloma patients receiving various standard approved treatments that aim at collecting tissue samples, genetic information, Quality of Life (QoL) and various disease and clinical outcomes over 10 years.

  Study phs000748

• Childhood Cancer Data Initiative (CCDI): Clonal Evolution During Metastatic Spread in High-Risk Neuroblastoma

  The goal of this study is to deliver a detailed characterization of the patterns of disease dissemination at diagnosis, during progression and in response to therapy in high-risk neuroblastoma. Longitudinal and spatially distinct tumors were collected from patients. Clinical data includes diagnosis and treatment information. Biospecimen data includes whole genome sequencing (WGS) and whole transcriptome sequencing (WTS).

  Study phs003111

• Myocardial Infarction Genetics Exome Sequencing Consortium: Ottawa Heart Study

  The Ottawa Heart Study is a cross-sectional case-control study designed to identify genes that predispose to angiographically defined coronary artery disease. All exome sequencing was performed at the Broad Institute of Harvard and MIT; samples sequence capture was performed using Agilent SureSelect Human All Exon Kit v2 and sequencing was performed on an Illumina HiSeq 2000 or 2500.

  Study phs000806

• Molecular Analysis of Alliance A031201 Study

  This is the first study examining the relationship between clonal hematopoiesis and clinical outcomes in prostate cancer patients. We used a targeted gene sequencing panel to identify patients in the A031201 clinical trial with and without clonal hematopoiesis. We found that clonal hematopoiesis did not affect overall or progression free survival in A031201 but was associated more adverse cardiac events.

  Study phs003717

• Mutational Profile in Newly Diagnosed Diffuse Large B-Cell Lymphoma: GAINED Study

  The GAINED study (NCT01659099) is a randomized phase 3 trial comparing obinutuzumab (G) to rituximab (R) in combination with ACVBP or CHOP14 induction, followed by PET-guided consolidation. This post-hoc analysis focuses on primary mediastinal B-cell lymphoma (PMBL) patients, confirmed through expert pathological review and characterized using gene-expression profiling (GEP) and Next-Generation Sequencing (NGS)

  Study EGAS50000000929

• Chromatin 3D interactions mediate genetic effects on gene expression

  Studying the genetic basis of gene expression and chromatin organization is key to characterize the effect of genetic variability on the function and structure of the human genome. Here, we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression and genetic variants across 317 individuals and two cell types.

  Study EGAS00001003485

• Bulk-mRNA sequencing comparing hiPSC derived vascular cells from CADASIL patient lines

  CADASIL is a hereditary brain small vessel disease caused by pathogenic variants in the NOTCH3 gene and causes degenration of Vascular Smooth Muscle cells in the brain. We performed bulk-mRNA sequencing and transcriptomic analysis from hiPSC derived vascular cells (hiPSC;Endothelial Cells; Neural Crest Cells; Vascular Smooth Muscle Cells) comparing CADASIL patient lines and respective isogenic-controls.

  Study EGAS50000001507

• SAIF Alignment File

  This is the bam file generated after alignment using BWA program for the SAIF genome

  Dataset EGAD00001000249

• Intrapatient tumor heterogeneity and clonal evolution in metastatic salivary gland cancer: an autopsy study: access to data

  Funded by the Radboud Oncology Fund and the Dr. C.J. Vaillant Fund, the Salivary Gland Cancer Autopsy research group (Research Group) has sequenced DNA of 17 salivary gland cancer samples of and three healthy control samples from three patients with salivary gland cancer. This research project is led by Carla M.L. van Herpen from Radboud University Medical Centre in Nijmegen, the Netherlands (“Radboudumc”). The DNA sequencing data have been used for an analysis of intrapatient tumor heterogeneity and clonal evolution of metastatic salivary gland cancer. The Research Group is willing to consider applications from third party researchers for access to the DNA sequence data. Access to the data will be granted to qualified researchers for approved use. Access to DNA Sequencing Data is available by application to the Data Access Committee (DAC). Researchers granted access to DNA Sequencing Data must feedback the results of their research to the Research Group, after publication in accordance with the Research Group publication policy set forth in the Data Access Agreement.

  Dac EGAC50000000792

• Somatic pseudogenes acquired during cancer development – RNAseq

  Insertion of processed pseudogenes is known to occur in the germline but has not previously been observed in somatic cells. Formation of pseudogenes could represent a new class of mutation in cancers and a new source of potential driver events.

  Dataset EGAD00001000639

• Comparison of 133/144bp dominant phenotype vs 166bp dominant phenotype.

  The sequencing results provided in this study is enriched through liquid phase hybridization capture. The data set shows 35 clinical cfDNA samples showing a dominant peak at 166bp and 35 clinical cfDNA samples showing a dominant peak at 134/144bp.

  Dataset EGAD00001005798

• DNA methylation (RRBS) data for the glioblastoma progression study (GBMatch).

  Genome-wide profiling of DNA methylation levels by RRBS in 349 samples, derived from 112 glioblastoma (IDH wildtype) patients, 13 IDH muated brain tumor patients, and 5 normal brain controls. For each patient samples from at least two and up to six tumor resections are available. For 6 patients multiple regions of each tumor were sampled.

  Dataset EGAD00001003427

• Genomic Characterization of Pediatric Low-Grade Gliomas

  Pediatric low-grade gliomas (PLGGs) are the most common pediatric brain-tumor, with more than ten histologic subtypes recognized by the World Health Organization. We performed a genomic analysis of 230 PLGGs of which 73 had whole genome/RNA sequencing performed and show that MYB-QKI fusions define the seizure associated tumor, Angiocentric Glioma (AG). MYB-QKI fusions present in AGs contribute to tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression, and hemizygous loss of QKI, a tumor suppressor gene. Such interplay between three oncogenic mechanisms has diagnostic and therapeutic implications in AGs, and illustrates the functional complexity associated with rearrangements in cancer.

  Study phs001054

• Pathologically Expanded Peripheral B Cell-Helper T Cells in Rheumatoid Arthritis

  PROSET-HD aims to identify and study immune cell populations altered in patients with autoimmune and inflammatory diseases. We have identified a population of PD-1hi CXCR5- 'peripheral helper' T (Tph) cells that are expanded in the joints and circulation of patients with seropositive rheumatoid arthritis. This T cell population uniquely combines potent B cell-helper function with a migratory program that directs homing to inflamed tissues. RNA sequencing was performed on sorted memory CD4+ T cell subpopulations to compare the global gene expression profiles of PD-1hi CXCR5- CD4+ T cells, PD-1hi CXCR5+ follicular helper T cells, and other T cell populations obtained from blood of rheumatoid arthritis patients.

  Study phs001262

• Somatic mutation rates scale with lifespan across mammals

  The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans. Comparative analyses can shed light on the diversity of mutagenesis across species and on long-standing hypotheses regarding the evolution of somatic mutation rates and their role in cancer and ageing. Here, we used whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found somatic mutagenesis to be dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans, although the relative contribution of each signature varied across species. Remarkably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied displaying a comparable association. Despite widely different life histories among the species surveyed, including ~30-fold variation in lifespan and ~40,000-fold variation in body mass, the somatic mutation burden at the end of lifespan varied only by a factor of ~3. These data unveil common mutational processes across mammals and suggest that somatic mutation rates are evolutionarily constrained and may be a determinant of lifespan.

  Dataset EGAD00001008032

• Skin Microbiome of Monogenic Skin Disorder

  Ichthyosis introduces multiple sources of disturbance to the skin, including the direct biochemical consequences of the genotype, the phenotypic changes in skin physiology, and an altered skin microbiome. The association between changes in the skin microbiome and the disease's genotypic and phenotypic effects are historically obscured. Here we characterize the skin microbiome of healthy participants and ichthyosis patients, before assessing the association between these microbiome features and the ichthyosis genotype and phenotype while adjusting for contextual host covariables.

  Study phs003799

• ESGI_Exome_sequencing_in_Circulating_Tumor_Cells_to_determine_therapy_related_markers_____

  The objectives of this project are the identification of markers related to cancer therapy resistance in the blood of breast cancer patients and to study the genetic changes in cancer cells during this development of resistance. Whole genome amplified DNA from Circulating Tumor Cells (CTCs), selected during the course of systemic treatment from blood of metastatic breast cancer patients, will be exome sequenced . The patients selected for this study did not respond to therapy.

  Study EGAS00001000747

• Immunogenomic landscape of hematological malignancies

  We integrated over 8,000 transcriptomes and over 2,000 samples with multilevel genomic data of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival. For more detailed follow-up analyses in acute myeloid leukemia (AML), single-cell RNA sequencing was performed on 8 AML bone marrow samples at diagnosis to profile the phenotypes of blasts and infiltrating immune cells in different disease subtypes.

  Study EGAS00001004444

• Investigation of the keratinocytic gene expression pattern in Hidradenitis suppurativa

  The underlying pathogenetic factors generating the innate immune signal necessary for T cell activation, initiation and chronification of Hidradenitis suppurativa (HS, also known as Acne inversa) are still poorly understood. Emerging evidence suggests that defective keratinocyte function critically contributes to HS disease development and progression. To elucidate the role of keratinocytes in HS lesion formation, we compared the transcriptomes of isolated lesional and perilesional HS epidermis by RNA sequencing.

  Study EGAS00001005544

• Cell types of the human retina and its organoids at single-cell resolution. Cowan et al

  Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers, and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas.

  Study EGAS00001004561

• Epithelioid haemangioendothelioma (EHE) case series from the Stafford Fox Rare Cancer Program

  Nine EHE cases with comprehensive histologic and molecular profiling from the Walter and Eliza Hall Institute of Medical Research Stafford Fox Rare Cancer Program were collated via nation-wide referral to the Australian Rare Cancer Portal. Molecular analysis of RNA, DNA or both was possible in seven of nine cases. Survival was highly variable and unrelated to molecular profile. DNA sequences for two cases are deposited here.

  Study EGAS00001007474

• NIDDK IBD Genetics Consortium Repository Immunochip

  The Immunochip is a custom Illumina Infinium chip comprising 196,524 SNPs and small indels selected primarily based on GWAS analysis of 12 autoimmune and inflammatory diseases. The chip has two purposes: fine mapping of 289 established associations corresponding to 187 distinct loci, and deep replication of suggestive, but not yet proven, associations. Fine-mapping regions were defined as 0.2cM centered on GWAS hit SNPs, and all SNPs and short indels in these regions from the 1000 Genomes Project low coverage pilot CEU samples, as well as variants discovered in resequencing experiments conducted by groups collaborating in the chip design were selected for inclusion. Replication of autoimmune and inflammatory GWAS (including Crohn's disease and ulcerative colitis) contributed the bulk of the remaining SNP lists. Approximately 25,000 SNPs were included as replication of unrelated diseases as part of the WTCCC2 project, which serve as useful null SNPs for these analyses. In total, approximately 240,000 SNPs were selected for inclusion, with an assay design success rate of ~80%. Reprinted from Jostins et al. (2012), with permission from Springer Nature (see https://www.nature.com/reprints/permission-requests.html). Jostins, L., et al. (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491, 119-24. PMID: 23128233.

  Study phs001721

• Single-cell and spatial atlas of steatotic liver disease-related hepatocellular carcinoma

  This study consists of the spatial transcriptomics data generated by : 1. Visium CytAssist Spatial Gene Expression for FFPE (10x) for steatotic liver disease-associated hepatocellular carcinoma (SLD-HCC) (n=7) and non-SLD-HCC (n=5) 2. CosMxTM Human Universal Cell Characterization RNA Panel (1000-plex); NanoString, USA for n=4 SLD-HCC and n=4 non-SLD-HCC. The goal of this data is to compare SLD-HCC vs non-SLD-HCC as well as response to immunotherapy

  Study EGAS50000001034

• Chicago Infant Mortality Study

  The Chicago Infant Mortality Study (CIMS) was a population-based, prospective, case-control study conducted in metropolitan Chicago, Cook County, Illinois, to examine the risk factors for sudden infant death syndrome (SIDS) among a primarily Black population. Eligible case infants were aged birth to one year where the cause of death was determined to be SIDS while eligible control infants were aged one month to one year who died of other sudden unexpected infant death (SUID) causes. Recruitment occurred between November 1993 and April 1996. The goal of this ancillary multiomics study was to evaluate possible genetic and epigenetic determinates of SIDS and together with metabolomic profiles, identify novel clinical diagnostic tools to enable molecular autopsies and biomarkers to proactively identify and intervene in infants at greater risk of death from SIDS. The multiomics data was generated from medical examiner autopsy specimens and includes: whole exome sequencing genotypes; RNA-seq transcriptome and methylome profiles from autopsy heart tissue; and serum metabolomics profiles. The sample size available varies with the modality of the omics assay, but the total number of unique infants included is about 400.

  Study phs003790

• HCA_Thymus_Disease

  Single cell RNA sequencing on thymic cells from children with syndromic diseases such as Trisomy 21 and inflammatory/autoimmune diseases such as myasthenia gravis. Our group has previously performed atlasing of the healthy human thymus using single cell transcriptomics and obtained an unprecedented understanding of human thymus throughout development. In this study, we intend to survey diseased human thymus and compare this to healthy to obtain a better understanding of thymic dysfunction in human diseases. The diseases we will survey include congenital conditions such as Down's syndrome, CHARGE syndrome, DiGeorge syndrome as well as acquired diseases such as myasthenia gravis and thymic hyperplasia. We intend to perform genetic and genomic study on the samples, including expression analysis. This will not only help us to understand the cells and molecular pathways affected in dysfunctional thymus; but may also lead to generalisable understandings in human genetic diseases and inflammatory/autoimmune 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/

  Study EGAS00001004310