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TIGER: the translational human pancreatic islet genotype tissue-expression resource

par Alonso, Lorena;Piron, Anthony ;Morán, Ignasi;Royo, Romina;Puiggròs, Montserrat;Guindo-Martínez, Marta;Bonàs-Guarch, Sílvia;Gloyn, Anna A.L.;Esguerra, Jonathan L S;Ferrer, Jorge;Marchetti, Piero;Eizirik, Decio L. ;Mercader, Josep Maria;Cnop, Miriam ;Torrents, David
Référence Annual Meeting of the European Association for the Study of Diabetes(56th: 21-25 September 2020: Virtual Congress), Diabetologia, Vol. 63, page (1–485)
Publication Publié, 2020-09-21

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Résumé :

Background and aims: The scarcity of human islets preparations from organ donors available and their scattering across research labs, limits the understanding of the genomic and regulatory landscape of human islets and type 2 diabetes (T2D). The Horizon 2020 T2DSystems Consortium set out to gather genomic, transcriptomic and epigenomic datasets from a large number of human pancreatic islet samples from several laboratories and make the data publicly available.Materials and methods: We collected RNA-seq and genotyping data from 495 human islet samples and performed harmonization, quality control, genotype phasing and imputation. We integrated a) T2D association from genome-wide association studies (GWAS) identified in large meta-analyses or included in the GWAS Catalog, b) variant annotation and characterization through Variant Effect Predictor and Gnomad, c) epigenomic marks from islet DNA-methylation sites, chromatin accessibility and CHiP-seq profiles, d) annotation from Gene Ontology, lncRNAs and islet regulome, e) gene expression from normalised islet RNA-seq counts, microarrays and the Genotype-Tissue Expression database, and f) computed expression quantitative loci (eQTL) and allelic specific expression (ASE) and created the largest regulatory variation database from human pancreatic islets.Results: We developed TIGER, a publicly accessible database (http://tiger.bsc.es) provided with a genome browser to ensure the comprehensive data integration. The platform encloses tools for visualizing, querying, and downloading human islet data. TIGER facilitates follow-up by providing genetic and molecular findings related to T2D pathophysiology with a gene or a variant summary, eQTL and ASE results, associations with T2D and other related traits or diseases, genomic context information such as the islet chromatin landscape and direct access to other genomic databases.Conclusion: The comprehensive collation in TIGER of genomic, transcriptomic and epigenetic human islet datasets, and the integration with T2D GWAS and regulatory variation, represents a formidable resource to interrogate the molecular etiology of beta-cell failure in T2D.