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• Whole Genome Sequencing of Skull-Based Chordoma

  Chordoma is a rare bone tumor, which is believed to originate from notochordal remnants. Based on the United States Surveillance Epidemiology and End Results (SEER) data, the incidence of chordoma varies by gender and race; however, little is known about the etiologic factors that predispose to it. Genomic profiling studies of chordoma are limited, particularly in the Chinese population. We therefore conducted a detailed molecular characterization of paired chordoma tumor/normal tissues using fresh frozen tissues and blood collected from skull-based Chinese chordoma patients. These analyses included whole exome sequencing and RNA sequencing analyses.

  Study phs002301

• dbGaP Collection: NHLBI Heart Failure Related dbGaP Data (No IRB requirement)

  The National Heart, Lung, and Blood Institute (NHLBI) Big Data Analysis Challenge: Creating New Paradigms for Heart Failure Research has concluded. The NHLBI will continue to make this collection of data available to the research community.Past information regarding the Data Collection for the NHLBI Big Data Analysis Challenge: Creating New Paradigms for Heart Failure Research is below.The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), is inviting novel Solutions for the NHLBI Big Data Analysis Challenge: Creating New Paradigms for Heart Failure Research. The goal of the challenge is to foster innovation in computational analysis and machine learning approaches utilizing large-scale NHLBI-funded datasets to identify new paradigms in heart failure research. The challenge aims to address the need for new open source disease models that can define sub-categorizations of adult heart failure to serve as a springboard for new research hypotheses and tool development in areas of heart failure research from basic to clinical settings. NHLBI has a history of making considerable investments in the creation of deep data resources including: long-standing, deeply-phenotyped epidemiological cohorts, innovative clinical trials, and large-scale precision medicine efforts that have generated whole genome sequencing and "other omics" data for more than one-hundred thousand individuals. To provide challenge participants with streamlined access to data across NHLBI's numerous studies containing heart failure data, the NHLBI has created this dbGaP study collection. Data access for this collection is controlled by NHLBI's Data Access Committee. Challenge participants are required to follow the use restrictions and acknowledgement instructions from the original dataset(s). Please note that the data in this collection are not harmonized across studies or otherwise altered from the original study. The NHLBI Big Data Analysis Challenge: Heart Failure Data Collection contains all NHLBI studies currently in dbGaP that contain data that may be relevant to research on heart failure. The studies in this collection are approved for General Research Use (GRU), Health/Medical/Biomedical Use (HMB), or Disease-Specific Use (DS) that permits research on heart failure. These studies span a variety of study designs, inclusion and exclusion criteria, sample sizes, and provide a wide breadth and depth of phenotype data on study participants. The available genomic data in these studies also varies, including genotyping arrays, sequencing (targeted, exome, whole genome), and additional -omic data (e.g., RNA or metabolite profiles). Please refer to each study's individual accession page to learn more about how study data were collected. Challenge participants are reminded that in addition to dbGaP, NHLBI's Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) contains other studies that have collected data relevant to heart failure and may wish to utilize BioLINCC data in the development of their Solution. Please refer to the individual accession page for each study in this collection to learn more about the history of each study.

  Study phs001991

• Altered oligodendrocyte heterogeneity in Multiple sclerosis revealed by single nuclei RNA sequencing

  This study is currently hosted by the European Nucleotide Archive. To access the data contained within the Study please follow the link below: https://www.ebi.ac.uk/ena/browser/view/PRJEB39323 Oligodendrocyte (OL) pathology is increasingly implicated in neurodegenerative diseases, as they are involved in metabolic support of axons and functional cross-talk with other brain cells. Rodent OLs are heterogeneous, with developmental and biological differences, but the extent of heterogeneity in the normal human brain and its contribution to any changes to disease remains unknown. Here we performed single nuclei RNA-sequencing (snRNA-seq) from white matter (WM) areas of post mortem human brain both in control (Ctr) and multiple sclerosis (MS) patients. We identified several sub-clusters of oligodendroglia in the Ctr human WM, some similar to those in mouse, and defined new markers for these cell states. Strikingly, some of these sub-clusters were under-represented in MS tissue, while others were more prevalent than in controls. We found a lack of OL precursor cells (OPCs) and an OL subcluster in an intermediate stage of differentiation in MS lesions and in normal appearing white matter (NAWM), suggesting either depletion by the disease or by a regenerative response. The differences in mature OL sub-clusters indicate different functional states of OLs in MS tissue and, as this is similar in NAWM to lesions, that MS is a more diffuse brain disease than the focal demyelinating lesions suggest. We were also able to identify new putative markers of different MS lesion subtypes. Our findings of an altered heterogeneity of oligodendroglia in MS may have an important contribution to our understanding of disease progression and may alter therapeutic approaches to MS.

  Study EGAS00001003412

• RNA-seq data from the EUROBATS Project in four tissues: Fat, LCL, Skin and whole Blood.

  EUROBATS consists of RNA-seq data for female twins in lisphoblastoide cell lines (LCL), abdominal adipose tissue (Fat), abdominal skin tissue (Skin) and whole blood (Blood). The samples are a combination of MZ twins, DZ twins and singletons. The goal of the project is to find biomarkers related with the ageing process and cellular senescence.

  Study EGAS00001000805

• European Genome-phenome Archive 15th Anniversary Celebration

  2023 marks the 15th Anniversary of the EGA, jointly managed by the European Bioinformatics Institute (EMBL-EBI) and the Centre for Genomic Regulation (CRG). To mark the occasion, a simultaneous celebration was held in both institutions on the 13th of December 2023. The teams gathered online to play a quiz game and celebrate all the achievements and milestones with two wonderful anniversary cakes. In 2008, the European Genome-phenome Archive was created at the EBI-EMBL in Cambridge to guarantee that human genome and phenome data were available to the international scientific community while data privacy was preserved. The six-person staff at the beginning of the project is now far behind us, with a team that reaches the number of 35 members. Since 2013, the European Bioinformatics Institute and the Centre for Genomic Regulation share responsibility for The European Genome-phenome Archive (EGA). At that time, the EGA had data for about 0,5 petabytes. Currently, the Archive contains more than 12 petabytes. 2023 comes to an end with several good news. The EGA has been renewed as an ELIXIR Core Data Resource. This was announced during the GA4GH 11th Plenary held in San Francisco last September when ELIXIR-Beacon was also confirmed to be a GA4GH Driver Project. Thus, the Beacon API has maintained this title since 2018. What’s more, the first Federated EGA dataset is now live on our website. This year we also launched new services for EGA users in September. By the numbers, in 2023 the EGA counts 2.5 PB archived, 371 studies published, 208 new submitters and 19 active projects in which the team is participating, among others. We look forward to continuing to support your research in 2024!

  Blog 15-anniversary

• 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

• Genomic and Transcriptomic Landscape of Fibrolamellar Hepatocellular Carcinoma

  Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare liver tumor primarily affecting adolescents and young adults. Little is known of the molecular pathogenesis. To characterize the disease we performed RNA sequencing and whole genome sequencing on FL-HCC tumors and adjacent normal tissue. The results demonstrate few consistent differences on the chromosomal level and many hundreds of alterations in the expression of RNA transcripts.

  Study phs000709

• Confirmation of a founder effect in a Northern European population (FRL) of a new beta-globin variant: HBB:c.23_26dup (codons 8/9 (+AGAA))

  Beta-thalassemia is a genetic disease caused by a defect in the production of the beta-like globin chain. More than 200 known different variants can lead to the disease and are mainly found in populations that have been exposed to malaria parasites. We recently described a duplication of 4 nucleotides in the first exon of beta-globin gene in several families of patients living in Nord-Pas-de-Calais (France). Using the genotypes at 12 microsatellite markers surrounding the beta-globin gene of four unrelated variant carriers plus an additional one recently discovered, we found that they shared a common haplotype indicating a founder effect that was estimated to have taken place 225 years ago (9 generations). In order to determine whether this variant arose in this region of Northern-Europe or was introduced by migrants from regions of the world where thalassemia is endemic, we genotyped the first 4 unrelated variant carriers and 32 controls from Nord-Pas-de-Calais for 97 European ancestry informative markers (EAIMs). Using these EAIMs and comparing with population reference panels, we demonstrated that the variant carriers were very similar to the controls and were closer to North European populations than to South European or Middle-East populations. Rare beta-thalassemia variants have already been described in patients sampled in non-endemic regions but it is the first proof of a founder effect in Northern Europe. The new genetic panel FRL is under registration in EGA.

  Study EGAS00001000980

• The Prediction and Prevention of Preeclampsia

  The Prediction and Prevention of Preeclampsia (PREDO) is a prospective birth cohort study of Finnish women who were pregnant between 2005 and 2010 and their children. The PREDO study cohort was set up to identify novel risk factors and biomarkers in pregnant women associated with the development of preeclampsia and intrauterine growth restriction (IUGR). Two groups of pregnant women were enrolled during the first trimester of their pregnancy: first, pregnant women with a known clinical risk factor status for preeclampsia and IUGR (N=1079; 969 of these women had at least one and 110 had none of the known risk factors for preeclampsia and IUGR), and second, pregnant women who volunteered to participate regardless of their risk factor status for preeclampsia and IUGR (N=3698). Both samples were monitored during pregnancy with four clinical visits and bi-weekly self-reports. The post-delivery follow-up has taken place at approximately 2 weeks, 6 months, and 3.5 years after the delivery. The most recent follow-up started in 2016 and is ongoing. In the high-risk sample, cord blood samples were collected and genome-wide genotyping has been conducted with Illumina OmniExpressExome 1.2 and genome-wide methylation status has been analysed with Illumina 450k HM array.

  Study EGAS00001001898

• In this study, blood-brain barrier (BBB)-forming brain endothelial-like cells were generated from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). Cells were subsequently exposed to focused ultrasound and microbubbles (FUS+MB) to induce BBB opening and their transcriptome analysed. RNA sequencing (RNA-seq) results demonstrated minimal changes in the gene expression following FUS+MB suggesting safety of FUS+MB application in the clinical setting.

  The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer’s disease (AD). Focused ultrasound applied together with microbubbles (FUS+MB) is a novel technique to transiently open the BBB and increase drug delivery. Evidence suggests that FUS+MB is safe, however the effects of FUS+MB on human BBB cells, especially in relation to AD, remain sparsely investigated. Here we developed a human sporadic AD BBB cell platform to investigate the effects of FUS+MB on BBB cells and screen for the delivery of two potentially therapeutic AD antibodies. We generated BBB cells from apolipoprotein E gene allele E4 (APOE4, high AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs). We utilized this robust and reproducible platform to demonstrate increased delivery of potentially therapeutic antibodies across the BBB, including an analogue of Aducanumab (AduhelmTM) following FUS+MB treatment. Our results also demonstrate the safety of FUS+MB indicated by minimal changes in the cell transcriptome as well as little or no changes in cell viability and inflammatory responses within first 24 h post FUS+MB, with potentially important implications in a clinical setting. Finally, we report a more physiologically relevant hydrogel-based 2.5D BBB model as a key development for FUS+MB-mediated drug delivery screening, with potentially higher translational utility. Our results provide an important advancement for identifying FUS+MB-deliverable drugs and screening for cell- and patient-specific effects of FUS+MB, accelerating its use as a therapy in AD.

  Study EGAS00001005944