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• Institut National de la Santé et de la Recherche Médicale U1016, Institut Cochin, Paris, France

  Dac EGAC00001000178

• MeDALL epigenetics study

  MeDALL- (Mechanisms of the Development of ALLergy) is a collaborative project supported by the European Union under the Health Cooperation Work Programme of the 7th Framework programme (grant agreement number 261357).MeDALL epigenetics study includes illumina 450k methylation measurements from 4 cohorts: Infancia y Medio Ambiente (INMA), Etudes des Déterminants pré et postnatals précoces du développement et de la santé de l’ENfant (EDEN), Children’s Allergy Environment Stockholm Epidemiology study(BAMSE), and Prevention and Incidence of Asthma and Mite Allergy (PIAMA)

  Study EGAS00001002169

• DAC for Central African ancient demography processes NGS dataset

  Title DAC Ancient tree-topologies and gene-flow processes among human lineages in Africa Contacts: Paul Verdu +33144057317 paul.verdu@mnhn.fr CNRS-MNHN-Université de Paris UMR7206 Eco-anthropology Short description The Data Access Committee for acess to genotype and sample information used in the article "Ancient tree-topologies and gene-flow processes among human lineages in Africa" by Gwenna Breton et al. 2025 ensures that data-access requests comply with the Informed Consent provided by donors, and with ethical and deontological guidelines with respect to privacy. DNA samples from individuals were collected with the subjects’ informed consent following the Declaration of Helsinki guidelines and approved by the following Ethics committees: Institut de Recherche pour le Développement (IRD, France); Cameroon Ministry of Scientific Research and Technology; Central African Republic Ministère de l’Enseignement Supérieur et de la Recherche Scientifique; France Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation (Comité de Protection des Personnes DC-2016-2740); French Commission Nationale Informatique et Liberté CNIL (declaration n°1972648); Uganda National Council for Science and Technology; Institutional Review Board of the University of Chicago Biological Sciences Division and the Pritzker School of Medicine University of Chicago Hospitals (protocol number 16986A); Committee for the Protection of Human Subjects of the Trustees of Dartmouth College and the Dartmouth-Hitchcock Medical Center (protocol number 22410); Human Research Ethics Committee (Medical) at the University of the Witwatersrand, Johannesburg (Protocol Numbers: M980553, M050902, M090576, M10270, M180654); Working Group of Indigenous Minorities in Southern Africa (WIMSA); South African San Council (SASC); and the Swedish Ethical Review Authority (Dnr 2019-05174). Requests for accessing all or part of the Central African data used in the article "Ancient tree-topologies and gene-flow processes among human lineages in Africa", by Gwenna Breton et al. 2024 (doi - PENDING), should be addressed to the DAC providing: 1) Data can only be used to explore human genetic evolution, evolutionary ecology and population history 2) The research institution where data will be stored and were analyses will be conducted. 3) The detailed coordinates of the researcher responsible for data storage and analyses. 4) A description (max 20 sentences) of the scientific finality and context of the project and classes of methodological analyses that will be performed to achieve it using the requested data. 5) When applicable, mention also other previously published data sets that will be used jointly with the requested datas et For accessing any or all the Central African genetic data used in the article "Ancient tree-topologies and gene-flow processes among human lineages in Africa", by Gwenna Breton et al. 2024 (doi - PENDING), the requester hereby ensures that: 1) Individual donor privacy should be respected at all times. Data cannot be made publicly available under any circumstances. 2) Data cannot be shared nor transferred to a third party without re-applying for eGA access to the DAC. 3) No direct or indirect commercial use of the data can be made 4) No individual medical genetics or disease diagnostics can be performed with the data 5) No medical or legal forensic investigations can be conducted with the data 6) No genealogical research can be conducted with the data (e.g. no paternity nor maternity testing, no genetic identification, no search of relatives using other datasets) 7) Appropriate citation of the article and data set used for any scientific communication using the data 8) Data is destroyed after the completion of the project. Any further re-use of the data is subject to a novel application to the DAC.

  Dac EGAC50000000447

• Botensilimab, an Fc-enhanced Anti-CTLA-4 Antibody, is Effective Against Tumors Poorly Responsive to Conventional Immunotherapy

  This study explores the genomic landscape associated with a novel Fc-engineered anti-CTLA-4 antibody (botensilimab) in advanced solid tumors. We seek to understand if enhancing the Fc-region affinity of anti-CTLA-4 antibodies can improve anti-tumor efficacy and expand clinical benefit to tumors poorly responsive to conventional immunotherapy. As part of an ongoing open-label, Phase 1, multicenter study, we conducted an exploratory sub-analysis of genomics data. The primary study evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of botensilimab monotherapy and in combination with an anti-PD-1 antibody (balstilimab) in participants with advanced solid tumors. RNA from formalin-fixed paraffin-embedded (FFPE) tumor biopsies and matched normal blood samples were isolated and subjected to RNA-sequencing using the Personalis ImmunoID NeXT Platform. We demonstrated that anti-CTLA-4 engineered for enhanced FcγR affinity leverages FcγR-dependent mechanisms to potentiate T cell responsiveness, reduce intratumoral Tregs, and enhance antigen presenting cell activation. This genomic analysis contributes to our understanding of the molecular mechanisms underlying patient responses to Fc-engineered anti-CTLA-4 therapy and may inform future strategies to expand the clinical benefit of immune checkpoint blockade in cancer immunotherapy.

  Study phs003704

• How are we funded?

  How are we funded? The EGA is provided infrastructure, administrative support, advisory input, and other relevant and necessary aspects by: CRG The EGA at the CRG is funded and supported by “La Caixa Foundation”, The Generalitat de Catalunya (Catalan Government), the Spanish Ministerio de Asuntos Económicos y Transformación Digital (Spanish Government) and the Instituto de Salud Carlos III. The Generalitat de Catalunya contributes with funding to the CRG and to the Barcelona Supercomputing Centre (BSC). The Barcelona Supercomputing Center is decisively contributing to EGA by providing the required compute, storage and networking resources, as well as key personnel for shared operations of EGA infrastructure. EMBL-EBI As part of the European Molecular Biology Laboratory (EMBL), the EGA at EMBL’s European Bioinformatics Institute receives funding from the governments of EMBL’s member states. The UK government, via UK Research and Innovation, also continues to support EMBL-EBI technical infrastructure, with EMBL supporting operational costs. A major source of funding for the EGA both at CRG and EMBL-EBI are competitive projects.The EGA resource continues to be funded through strategic engagement in collaborative partnerships and projects. Please see our projects page for more information. Other funders include the European Commission, the US National Institutes of Health, the Wellcome Trust, UK Research Councils, and our Industry Programme partners. Last updated on October, 2024.

  Documentation about/projects-and-funders/funders

• Fgl2 Regulates FcγRIIB+ CD8+ T Cell Responses during Infection

  While the inhibitory receptor FcγRIIB has been shown to be upregulated on activated CD8+ T cells in both mice and humans, its impact on T cell fate during infection has not been fully elucidated. We identified an increase in FcγRIIB-expressing CD8+ T cells in COVID patients relative to healthy controls, and in mouse models of viral infection. Despite its well-known role as an Fc receptor, FcγRIIB also ligates the immunosuppressive cytokine Fgl2, resulting in CD8+ T cell apoptosis. Both chronic LCMV infection in mice and COVID in humans resulted in a significant increase in plasma Fgl2. Further, plasma Fgl2 was directly proportional to CD8+ T cell lymphopenia in COVID patients. To further understand the association of Fgl2 and CD8+ T cell lymphopenia following COVID infection, we assessed the transcriptomic profiles of PBMCs with high (≥ 9.153 ng/ml) vs low (defined as

  Study phs003870

• OV04 chemo prediction

  Predicting resistance to chemotherapy using chromosomal instability signatures Joe Sneath Thompson1,2,*, Laura Madrid2,*, Barbara Hernando1,*, Carolin M. Sauer3, Maria Vias3, Maria Escobar-Rey1,2, Wing-Kit Leung2,3, Diego Garcia-Lopez2, Jamie Huckstep3, Magdalena Sekowska3, Karen Hosking4,5, Mercedes Jimenez-Linan5,6, Marika A. V. Reinius3,5,6, Abhipsa Roy2, Omar Abdulle2, Justina Pangonyte3, Harry Dobson2, Amy Cullen2,3, Dilrini De Silva2, David Gómez-Sánchez1,7, Marina Torres1, Ángel Fernández-Sanromán1, Deborah Sanders3, Filipe Correia Martins3,5,6, Ionut-Gabriel Funingana3,4,5, Giovanni Codacci-Pisanelli3,4,8, Miguel Quintela-Fandino1, Florian Markowetz2,3,4, Jason Yip2, James D. Brenton2,3,4,5,6, Anna M. Piskorz#,2,3, Geoff Macintyre#,1,2 1 Spanish National Cancer Research Centre (CNIO), Madrid, Spain 2 Tailor Bio Ltd, Cambridge, UK 3 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK 4 Department of Oncology, University of Cambridge, Cambridge, UK 5 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK 6 Cancer Research UK Major Centre - Cambridge, University of Cambridge, Cambridge, UK 7 H12O-CNIO Lung Cancer Clinical Research Unit, Health Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain 8 University of Rome "la Sapienza", Rome, Italy

  Dac EGAC50000000612

• Data Access Committee KCL FC

  Dac EGAC00001000386

• MCF10A 12h IL6 classical signaling

  Gene expression after cell culture, 12h IL6+sgp130-Fc stimulated

  Dataset EGAD00010001970

• MCF10A 24h IL6 classical signaling

  Gene expression after cell culture, 24h IL6+sgp130-Fc stimulated

  Dataset EGAD00010001963

• CIP: Obesity-Diabetes Familial Risk, Viva La Familia Study

  The VIVA LA FAMILIA Study was designed to identify genetic variants influencing childhood obesity and its comorbidities in the Hispanic population. Family recruitment and phenotyping were conducted in 2000-2005 in Houston, TX. All enrolled children (n=1030) and parents gave written informed consent or assent. The protocol was approved by the Institutional Review Boards for Human Subject Research for Baylor College of Medicine and Affiliated Hospitals and for Texas Biomedical Research Institute. The VIVA LA FAMILIA study design and methodology have been described in detail (Butte NF, 2006). Each family was ascertained on an obese proband, defined as a BMI > 95th percentile, between the ages 4-19 y. The cross-sectional, longitudinal study design consisted of baseline measurements, with a one-year. GWAS was performed using the Illumina HumanOmni1 v1.0 BeadChips on 815 children from 263 Hispanic families and HumanOmni 2.5-8v1 on an additional 43 children. Exome sequencing is being performed on 822 children using NimbleGen capture, followed by Illumina DNA sequencing. Butte NF, Cai G, Cole SA, Comuzzie AG. Viva la Familia Study: genetic and environmental contributions to childhood obesity and its comorbidities in Hispanic population. Am J Clin Nutr 2006;84(3):646-54. PMID: 16960181

  Study phs000616

• Native_American_Ancient_DNA_sequencing

  The morphology of the first humans in the Americas (Paleoamericans) differs from that of Native Americans, and has raised the question of whether or not there are also differences in origin or genetics. A few populations who survived until relatively recently have been suggested to retain Paleoamerican morphology. One of these populations is from La Jolla. Here, we have generated genome sequence data from four La Jolla individuals in order to investigate these questions 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 EGAS00001001802

• Institut National pour la Recherche Biomedicale Comite d'Access aux Donnees

  Dac EGAC00001001539

• AREP(Association pour la Recherche et l’Enseignement en Pathologie) Data Access Commitee

  Dac EGAC00001001196

• Team

  The Team Mallory Freeberg Roderic Guigó Arcadi Navarro Helen Parkinson Jordi Rambla Ana T. Alonso Silvia Bahena Àlex Bedmar Kenneth Buckley Aldar Cabrelles Ángel Carreño Marcos Casado Giulia Cellerino Amy Curwin Teresa D'Altri Abeer Fadda Teresa Garcia Sara Gregorio Max Fischer Bela Juhasz Oriol Lopez-Doriga Mireia Marin Óscar Martínez Andrea Mero Akiris Moctezuma Aurora Moreno Liina Nagirnaja Francesc de Puig Santiago Rensonnet Gabriele Rinck Aravind Sankar Andres Silva Coline Thomas Sabela de la Torre Gemma Vicente The EGA Team at the CRG co-manages the European Genome and phenome Archive together with the EGA Team at the European Bioinformatics Institute. In addition to maintaining and distributing data, we enrich the contents of the EGA contributing with our knowledge about genomics and the relationship between genomes and phenomes. Previous Team Members Alexander Vikhorev Jeff Almeida-King Mario Alberich Sergi Aguilo Pablo Arce Minjie Ding Alfred Gil Leslie Glass Jag Kandasamy Vasudev Kumanduri llkka Lapalainen Audald Lloret i Villas Sira Martinez Anand Mohan Dietmar Orth Justin Paschall Saif Ur Rehman Gary Saunders Thomas Smith Ashutosh Shimpi Marc Sitges Dhvani Solanki Giselle Kerry Nino Spataro Dylan Spalding Matthieu Vizuete-Forster Cristina Yenyxe Gonzalez Garcia Paul Flicek Anna Foix Emilio Garcia Rios Jorge Izquierdo Roberto Ariosa Marta Ferri Peradalta Daniel Barrowdale Babita Singh Umuthan Uyan Aleix Canalda Dona Shaju Mauricio Moldes Carles Garcia Frédéric Haziza Alegria Aclan Lauren Fromont Alvis Brazma Marta Huertas Arnau Soler Gemma Milla Claudia Vasallo Aina Jené Csaba Halmagyi Raül Garcia Thomas Keane Mei Gascón

  Documentation about/team

• The Genetic Basis of Aggressive Prostate Cancer, The Role of Rare Variation

  In this study, we will apply a multi-staged approach to reveal genes harboring rare variants that are associated with aggressive PCa. Whole-exome sequencing (Aim 1a) of 2,774 aggressive cases and 2,776 non-aggressive cases of European ancestry will be conducted followed by rare variant analysis of single sites and gene burden testing to identify novel susceptibility loci/genes for aggressive disease. We will validate the most significantly associated genes (~500) through targeted sequencing in an additional 6,415 aggressive and 5,586 non-aggressive cases and 1,890 controls (Aim 1b). Next, we will investigate the clinical predictive utility of the genes/variants identified in 2,291 cases in the STHM3 trial who are undergoing biopsy based on PSA and genetic risk score stratification (Aim 2). Through this tiered approach we expect to significantly advance knowledge of aggressive PCa etiology and health disparities as well as guide the development of early detection and prognostic strategies for the subset of men who are most susceptible to this fatal form of disease. In this case-case study of aggressive vs non aggressive prostate cancer, aggressive cases are defined as prostate cancer as cause of death, (T4 disease or T3 disease) and Gleason 8+. Non-aggressive cases are men with T1/2 disease and Gleason ACKNOWLEDGMENTS and CONTRIBUTING SITES CAPS, PROCAP, STHM1, STHM2: Swedish Cancer Society (CAN 2016/818), Swedish Research Council (2014/2269).STHM3: Stockholm County Council (Stockholms Läns Landsting).MEC: Funding provided by the National Cancer Institute: Understanding Ethnic Differences in Cancer, 2U01CA164973 and The Genetic Basis of Aggressive Prostate Cancer, The Role of Rare Variation, 5R01CA196931-02.ATBC: The ATBC Study is supported by the Intramural Research Program of the U.S. National Cancer Institute, National Institutes of Health, and by U.S. Public Health Service contract HHSN261201500005C from the National Cancer Institute, Department of Health and Human Services.COSM: The Swedish Research Council/National Research Infrastructure Grant (VR 2014/6397; VR 2015/5997) The Swedish Cancer Foundation (CAN 2013/456; CAN 2016/727)CPSII: The authors express sincere appreciation to all Cancer Prevention Study II participants and to each member of the study and biospecimen management group. The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study-II cohort.MCCS/APCS/PCFS: The Melbourne Collaborative Cohort Study (MCCS) recruitment was funded by VicHealth and Cancer Council Victoria and further supported by Australian National Health and Medical Research Council (NHMRC) grants 209057 and 396414. The Aggressive Prostate Cancer Case-Control Study (APCS) was funded by NHMRC grant 623204. The Prostate Cancer Family Study (PCFS) was fully funded by Cancer Council Victoria. Cancer Council Victoria funds the continuing maintenance and updating of the MCCS, APCS and PCFS. Cases and their vital status are ascertained and followed up through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database.PLCO: The Prostate Lung Colorectal Ovarian Cancer Screening Trial (PLCO) was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, US National Institutes of Health, Department of Health and Human Services. EPIC: The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam- Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A19170 and C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom). DFCI: Linda and Arthur Gelb and Rebecca and Nathan Milikowsky. HPFS and PHS: The Health Professionals Follow-up Study was supported by U01 167552 and P01 CA228696 from the National Cancer Institute, and with support from the Prostate Cancer Foundation. The Physicians' Health Study was supported by grants CA34944, CA40360, CA097193, HL26490 and HL34595.Northwestern: P50CA180995 (Catalona) 08/01/15 – 07/31/20 NIH/NCI SPORE in Prostate Cancer; The Urological Research FoundationPROMPT: MRC UK - Project reference G0500966, Cambridge BRC infrastructure funding, Cambridge Biomedical Research Campus (BRC-1215-20014), CRUK Cambridge Cancer Centre infrastructure funding (they are requesting this statement is written in blue for publications).ICR: This work was supported by the NIH R01 grant 5R01CA196931-02. The samples from the UK were from UKGPCS and PrompT. The UKGPCS study was supported by Cancer Research UK (grant numbers C5047/A7357, C1287/A10118, C1287/A5260, C5047/A3354, C5047/A10692, C16913/A6135 and C16913/A6835). We would like to acknowledge the NCRN nurses and Consultants for their work in the UKGPCS study. We thank all the patients who took part in this study. We also acknowledge The Institute of Cancer Research, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI) UK for their ongoing support. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.Funding:CIDR grant X01HG008336

  Study phs001524

• Chun Lab DAC

  Data Access Committee (DAC) for datasets produced by the Chun Lab @ Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California.

  Dac EGAC50000000011

• Native American Ancient DNA sequencing

  The morphology of the first humans in the Americas (Paleoamericans) differs from that of Native Americans, and has raised the question of whether or not there are also differences in origin or genetics. A few populations who survived until relatively recently have been suggested to retain Paleoamerican morphology. One of these populations is from La Jolla. Here, we have generated genome sequence data from four La Jolla individuals in order to investigate these questions 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 EGAD00001002144

• Characterization of a human iPSC-derived endocrine pancreas model

  Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at six stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from two donors, and characterized the distinct transcriptomic profiles associated with each stage. Established regulators of endodermal lineage commitment, such as SOX17 (log2 fold change [FC] compared to iPSCs=14.2, p-value=4.9x10-5) and the pancreatic agenesis gene GATA6 (log2 FC=12.1, p-value=8.6x10-5), showed transcriptional variation consistent with their known developmental roles. However, these analyses highlighted many other genes with stage-specific expression patterns, some of which may be novel drivers or markers of islet development. For example, the leptin receptor gene, LEPR, was most highly expressed in published data from in vivo-matured cells compared to our endocrine pancreas-like cells (log2 FC=5.5, p-value=2.0x10-12), suggesting a role for the leptin pathway in the maturation process. Endocrine pancreas-like cells showed significant stage-selective expression of adult islet genes, including INS, ABCC8, and GLP1R, and enrichment of relevant GO-terms (e.g. "insulin secretion"; odds ratio=4.2, p-value=1.9x10-3): however, principal component analysis indicated that in vitro-differentiated cells were more immature than adult islets. Integration of the stage-specific expression information with genetic data from T2D genome-wide association studies revealed that 46 of 82 T2D-associated loci harbor genes present in at least one developmental stage, facilitating refinement of potential effector transcripts. Together, these data show that expression profiling in an iPSC islet development model can further understanding of islet biology and T2D pathogenesis.

  Study EGAS00001001803

• Dedifferentiated Melanoma (2021-02-02)

  De- and transdifferentiation of melanoma is a rare histopathological phenomenon that has not be characterised genetically. In this project we plan to sequence the genomes of de and transdifferentiated cases so as to define their genetic make-up. . This dataset contains all the data available for this study on 2021-02-02.

  Dataset EGAD00001006931

• Anti-TIGIT antibody tiragolumab improves PD-L1 blockade via myeloid and Treg cells

  Tiragolumab, an anti-TIGIT antibody with an active IgG1/kappa Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (NCT03563716) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone1. However, there remains little consensus on the mechanism(s) of response with this combination2. We found that high baseline intratumoral macrophages and Tregs were associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation was associated with clinical benefit in patients receiving the combination treatment. In mouse tumor models, tiragolumab surrogate antibodies inflamed tumor-associated macrophages, monocytes, and dendritic cells through Fc gamma receptors (FcɣR), in turn driving anti-tumor CD8+ T cells from an exhausted effector-like state to a more memory-like one. These results uncover a mechanism of action by which TIGIT checkpoint inhibitors can remodel immunosuppressive tumor microenvironments, and suggest that FcɣR engagement is an important consideration in anti-TIGIT antibody development.

  Study EGAS50000000251

• SF3B1 splicing signature

  We describe individuals with de novo pathogenic variants in SF3B1. SF3B1 is a core component of the U2 snRNP complex that ensures accurate branchpoint and 3′ splice-site recognition, and its mutations induce aberrant splicing that contributes to tumorigenesis, notably in myelodysplastic syndromes. We aim to study splicing defects associated with constitutional pathogenic variants.

  Study EGAS50000001473

• Expression profiling of a human endocrine pancreas iPSC model

  Directed differentiation of stem cells offers a scalable solution to the need for human cell models recapitulating islet biology and T2D pathogenesis. We profiled mRNA expression at six stages of an induced pluripotent stem cell (iPSC) model of endocrine pancreas development from two donors, and characterized the distinct transcriptomic profiles associated with each stage. Established regulators of endodermal lineage commitment, such as SOX17 (log2 fold change [FC] compared to iPSCs=14.2, p-value=4.9x10-5) and the pancreatic agenesis gene GATA6 (log2 FC=12.1, p-value=8.6x10-5), showed transcriptional variation consistent with their known developmental roles. However, these analyses highlighted many other genes with stage-specific expression patterns, some of which may be novel drivers or markers of islet development. For example, the leptin receptor gene, LEPR, was most highly expressed in published data from in vivo-matured cells compared to the endocrine pancreas-like cells (log2 FC=5.5, p-value=2.0x10-12), suggesting a role for the leptin pathway in the maturation process. Endocrine pancreas-like cells showed significant stage-selective expression of adult islet genes, including INS, ABCC8, and GLP1R, and enrichment of relevant GO-terms (e.g. “insulin secretion”; odds ratio=4.2, p-value=1.9x10-3): however, principal component analysis indicated that in vitro-differentiated cells were more immature than adult islets. Integration of the stage-specific expression information with genetic data from T2D genome-wide association studies revealed that 46 of 82 T2D-associated loci harbor genes present in at least one developmental stage, facilitating refinement of potential effector transcripts. Together, these data show that expression profiling in an iPSC islet development model can further understanding of islet biology and T2D pathogenesis.

  Dataset EGAD00001002148

• Ribo-depleted RNA-sequencing of II.3, III.1, and III.3

  This datasets contains the Ribo-depleted RNA-sequencing of patients II.3, III.1, and III.3. Libraries were sequenced to a minimum depth of 195 million read pairs (2x75nts) on an Illumina NextSeq500 Midoutput FC.

  Dataset EGAD50000002364

• Epidemiologic Architecture for Genes Linked to Environment (EAGLE) MetaboChip Study

  The Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study is a study site of the larger Population Architecture using Genomics and Epidemiology (PAGE) I study.  EAGLE accessed two data resources during the course of study: the National Health and Nutrition Examination Surveys (NHANES) and BioVU, the Vanderbilt University Medical Center biorepository linked to de-identified electronic health records.The EAGLE MetaboChip Study, also known as EAGLE BioVU in the literature, is a data resource of Illumina MetaboChip genotypes for ~15,000 DNA samples from African American/Black, Hispanic, and Asian patients in BioVU (PMID: 26201699). Several EAGLE BioVU and PAGE I study phenotypes were extracted using structured and unstructured data available in de-identified electronic health records linked to the DNA samples. 

  Study phs002767