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

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

  Study EGAS00001005634

• Illumina HumanOmniExpress genotyping data from the TEENAGE (TEENs of Attica: Genes and Environment) study.

  The TEENAGE study is a cross-sectional study comprising healthy Greek adolescents. The study was conducted according to the guidelines specified in the Declaration of Helsinki and all procedures involving human subjects were approved by the Institutional Review Board of Harokopio University and the Greek Ministry of Education, Lifelong Learning and Religious Affairs. The TEENAGE study target population comprised adolescent students aged 13 to 15 years attending the first three classes of public secondary schools located in the wider Athens area of Attica. The regions across Attica from which students were recruited were physically similar and all urban in nature. Sampling of regions and schools selected to participate was random. Students were enrolled from the wider urban region to ensure that they were coming from families with varying educational background and socio-economic status. Moreover, in order to exclude any vast economic disparities, all participating schools were exclusively public schools, which are free of charge. A total of twenty-four schools participated in the study out of 285 junior secondary public schools in Attica. Anthropometric, medical and dietary information was obtained. DNA samples were genotyped using Illumina HumanOmniExpress BeadChips (Illumina, San Diego, CA, USA) at the Wellcome Trust Sanger Institute, Hinxton, UK. Genotype calling algorithm used was Illuminus (Teo et al., 2007).

  Study EGAS00001000996

• Adipose transcriptome response after a 6-day very-low energy fast in obesity, in the single-arm feeding trial FASTOMICS-6

  Background: Fasting and ketogenic diets have gained popularity due to potential health benefits, in part via autophagy and other protective processes. However, although the basic physiology of fasting is well-established, we lack a deeper understanding of mechanisms on the tissue level and associated metabolome changes, particularly in humans. Method: 4 males and 9 females with severe obesity underwent a very-low-energy in-hospital feeding study (600 kcal/day). Plasma (n=13) and subcutaneous adipose tissue samples (n=12) were collected in the morning before and after 6 days and analyzed by GC-MS/MS and RNA-sequencing, respectively. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis were used to identify biological pathways and modules of affected genes and their correlation with plasma ketones and metabolites.

  Dataset EGAD50000001484

• Somatic L1 retrotransposition in normal colorectal epthelium

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

  Dataset EGAD00001010183

• Multi-omics analysis defines core genomic alterationsin pheochromocytomas and paragangliomas

  Pheochromocytomas and paragangliomas (PCC/PGL) are neural crest derived tumors with a very strong genetic component. We report the first integrated genomic portrayal of a large collection of PCC/PGL. SNP array analysis revealed distinct copy-number patterns associated with genetic background. Whole-exome sequencing showed a low mutation rate of 0.3 mutations per megabase, with few recurrent somatic mutations in genes not previously associated with PCC/PGL. DNA methylation arrays and miRNA sequencing identified DNA methylation changes and miRNA expression clusters strongly associated with mRNA expression profiling. Overexpression of the miRNA cluster 182/96/183 was specific of SDHB-mutated tumors and induced invasive traits, whereas silencing of the imprinted DLK1-MEG3 miRNA cluster appeared as a potential driver in a subgroup of sporadic tumors. Altogether, the complete genomic landscape of PCC/PGL is mainly driven by distinct germline and/or somatic mutations in susceptibility genes and reveals different molecular entities, characterized by a set of unique genomic alterations.

  Dataset EGAD00001000986

• Massachusetts General Hospital/Eisai National Institute of Mental Health (NIMH) Genetics Initiative Alzheimer's Disease GWAS - Affymetrix GeneChip Human Mapping 500K Array Set

  This study cohort was collected as part of the National Institute of Mental Health (NIMH) Alzheimer's disease Genetics Initiative Study. Recruitment of families, predominantly sibling, for the cohort was focused on local memory disorder clinics, nursing homes, and the surrounding community. Clinical evaluation was performed at the University of Alabama at Birmingham, Johns Hopkins University, and Massachusetts General Hospital/Harvard Medical School. Informed consent was obtained from all study participants, for participants with extensive cognitive impairment, a legal guardian or caregiver with power of attorney provided consent. To determine age of onset, a creditable informer was interviewed and medical records were evaluated.

  Study phs000483

• Stressors and Health Study

  ObjectivesThe objectives of the Stressors and Health Study were to: (1) examine the prevalence of stressors and health outcomes and (2) assess differences in the associations between multi-level stressors and health outcomes, and (3) explore the protective and adaptive factors in the associations between multi-level stressors and health outcomes. Background Stressors have been posited to explain disparities in health. However, no surveys to our knowledge have simultaneously collected multiple stressors at various levels and the coping strategies used to deal with these stressors. Measuring these factors can provide a better understanding of the stressors experienced by specific groups and the impact that these experiences have on their health and health practices. In addition, exploring the various resilience and coping strategies employed to deal with stressors can help design appropriate interventions to reduce health disparities. Participants Participants included 1000 White, 1000 Black or African American, 1000 Latino or Hispanic, 1000 Asian, 500 American Indian or Alaska Native, 500 Native Hawaiian or Pacific Islander, and 500 mixed or multi-race adults (≥18 years) across the United States. Design The Stressors and Health Study is a cross-sectional online survey of adults across the US. A sampling frame (target population) of US residents based on the American Community Survey (ACS) was constructed using a rigorous two-step sampling matching approach to establish national representation.

  Study phs004019

• Gene-Specific RNA Sequencing in PLCG2-Associated Immune Dysregulation with Cold Urticaria

  This study utilized gene-specific RNA-sequencing of PLCG2 to screen for disease causing in-frame exon-skipping transcripts of PLCG2 in a collection of 9 subjects with cold urticaria, 2 subjects with known PLCG2-associated antibody deficiency and immune dysregulation (PLAID)-causing deletions of PLCG2 (positive controls) and 3 healthy subjects (negative controls). Full length cDNA of PLCG2 was generated using gene specific reverse transcription of peripheral blood mononuclear cell RNA. The full length PLCG2 cDNA was used as the template to create Illumina sequencing libraries. To identify the underlying genetic basis for the exon-skipping transcripts, trio-based whole genome sequencing was performed for probands in whom in-frame exon-skipping transcripts of PLCG2 were identified.

  Study phs003807

• Chromatin 3D interactions mediate genetic effects on gene expression (ChIP-seq)

  ChIP-seq data for Lymphoblastoid Cell Lines (LCL) and Fibroblasts (FIB) from the Gencord Cohort: - 160 LCLs assayed for H3K27ac, H3K4me1 and H3K4me3, - 78 FIB assayed for H3K4me3 and 79 FIB assayed for H3K27ac and H3K4me1 This dataset was generated as part of the following study: Delaneau et al (2019). Chromatin 3D interactions mediate genetic effects on gene expression.

  Dataset EGAD00001004871

• Familial breast cancer targeted sequencing with ONT

  A large cohort of 600 cases with familial breast cancer as classified by the Spanish Society of Medical Oncology (SEOM) Clinical Guidelines Update that were recruited during 6 years at Hospital Universitario Morales Meseguer (Murcia, Spain) were retrospectively evaluated to select 16 cases with no positive finding in NGS analysis of 20 genes implicated in this disease. These 16 cases were selected for further investigation using nanopore sequencing. This method involved the use of adaptive sampling enrichment, targeting a panel of 18 human genome regions, which contained the 20 genes (PTEN, ATM, BRCA2, PALB2, CDH1, TP53, NF1, RAD51D, BRCA1, RAD51C ,BRIP1, STK11, CHEK2, EPCAM, MSH2, MSH6, BARD1, MLH1, PMS2, NBN). In 5 samples (P1, P2, P4, P15 and P16) no selection of long reads was performed. Additionally, in 3 samples (P7, P9 and P10), both procedures were performed in two independent runs, and for the second run of P7, the DNA was previously fragmented using g-TUBE Covaris® (ref 520079) according to the protocol for 6 kb fragments.

  Dataset EGAD00001011106