Biomedical Data Commons (BMDC) prioritizes B-lymphocyte non-coding genetic variants in Type 1 Diabetes.

The repurposing of biomedical data is inhibited by its fragmented and multi-formatted nature that requires redundant investment of time and resources by data scientists. This is particularly true for Type 1 Diabetes (T1D), one of the most intensely studied common childhood diseases. Intense investig...

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Autores principales:	Samantha N Piekos, Sadhana Gaddam, Pranav Bhardwaj, Prashanth Radhakrishnan, Ramanathan V Guha, Anthony E Oro
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/156a7a24928640d481d412773f7836ef
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spelling	oai:doaj.org-article:156a7a24928640d481d412773f7836ef2021-12-02T19:57:45ZBiomedical Data Commons (BMDC) prioritizes B-lymphocyte non-coding genetic variants in Type 1 Diabetes.1553-734X1553-735810.1371/journal.pcbi.1009382https://doaj.org/article/156a7a24928640d481d412773f7836ef2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009382https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The repurposing of biomedical data is inhibited by its fragmented and multi-formatted nature that requires redundant investment of time and resources by data scientists. This is particularly true for Type 1 Diabetes (T1D), one of the most intensely studied common childhood diseases. Intense investigation of the contribution of pancreatic β-islet and T-lymphocytes in T1D has been made. However, genetic contributions from B-lymphocytes, which are known to play a role in a subset of T1D patients, remain relatively understudied. We have addressed this issue through the creation of Biomedical Data Commons (BMDC), a knowledge graph that integrates data from multiple sources into a single queryable format. This increases the speed of analysis by multiple orders of magnitude. We develop a pipeline using B-lymphocyte multi-dimensional epigenome and connectome data and deploy BMDC to assess genetic variants in the context of Type 1 Diabetes (T1D). Pipeline-identified variants are primarily common, non-coding, poorly conserved, and are of unknown clinical significance. While variants and their chromatin connectivity are cell-type specific, they are associated with well-studied disease genes in T-lymphocytes. Candidates include established variants in the HLA-DQB1 and HLA-DRB1 and IL2RA loci that have previously been demonstrated to protect against T1D in humans and mice providing validation for this method. Others are included in the well-established T1D GRS2 genetic risk scoring method. More intriguingly, other prioritized variants are completely novel and form the basis for future mechanistic and clinical validation studies The BMDC community-based platform can be expanded and repurposed to increase the accessibility, reproducibility, and productivity of biomedical information for diverse applications including the prioritization of cell type-specific disease alleles from complex phenotypes.Samantha N PiekosSadhana GaddamPranav BhardwajPrashanth RadhakrishnanRamanathan V GuhaAnthony E OroPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 9, p e1009382 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Samantha N Piekos Sadhana Gaddam Pranav Bhardwaj Prashanth Radhakrishnan Ramanathan V Guha Anthony E Oro Biomedical Data Commons (BMDC) prioritizes B-lymphocyte non-coding genetic variants in Type 1 Diabetes.
description	The repurposing of biomedical data is inhibited by its fragmented and multi-formatted nature that requires redundant investment of time and resources by data scientists. This is particularly true for Type 1 Diabetes (T1D), one of the most intensely studied common childhood diseases. Intense investigation of the contribution of pancreatic β-islet and T-lymphocytes in T1D has been made. However, genetic contributions from B-lymphocytes, which are known to play a role in a subset of T1D patients, remain relatively understudied. We have addressed this issue through the creation of Biomedical Data Commons (BMDC), a knowledge graph that integrates data from multiple sources into a single queryable format. This increases the speed of analysis by multiple orders of magnitude. We develop a pipeline using B-lymphocyte multi-dimensional epigenome and connectome data and deploy BMDC to assess genetic variants in the context of Type 1 Diabetes (T1D). Pipeline-identified variants are primarily common, non-coding, poorly conserved, and are of unknown clinical significance. While variants and their chromatin connectivity are cell-type specific, they are associated with well-studied disease genes in T-lymphocytes. Candidates include established variants in the HLA-DQB1 and HLA-DRB1 and IL2RA loci that have previously been demonstrated to protect against T1D in humans and mice providing validation for this method. Others are included in the well-established T1D GRS2 genetic risk scoring method. More intriguingly, other prioritized variants are completely novel and form the basis for future mechanistic and clinical validation studies The BMDC community-based platform can be expanded and repurposed to increase the accessibility, reproducibility, and productivity of biomedical information for diverse applications including the prioritization of cell type-specific disease alleles from complex phenotypes.
format	article
author	Samantha N Piekos Sadhana Gaddam Pranav Bhardwaj Prashanth Radhakrishnan Ramanathan V Guha Anthony E Oro
author_facet	Samantha N Piekos Sadhana Gaddam Pranav Bhardwaj Prashanth Radhakrishnan Ramanathan V Guha Anthony E Oro
author_sort	Samantha N Piekos
title	Biomedical Data Commons (BMDC) prioritizes B-lymphocyte non-coding genetic variants in Type 1 Diabetes.
title_short	Biomedical Data Commons (BMDC) prioritizes B-lymphocyte non-coding genetic variants in Type 1 Diabetes.
title_full	Biomedical Data Commons (BMDC) prioritizes B-lymphocyte non-coding genetic variants in Type 1 Diabetes.
title_fullStr	Biomedical Data Commons (BMDC) prioritizes B-lymphocyte non-coding genetic variants in Type 1 Diabetes.
title_full_unstemmed	Biomedical Data Commons (BMDC) prioritizes B-lymphocyte non-coding genetic variants in Type 1 Diabetes.
title_sort	biomedical data commons (bmdc) prioritizes b-lymphocyte non-coding genetic variants in type 1 diabetes.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/156a7a24928640d481d412773f7836ef
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Biomedical Data Commons (BMDC) prioritizes B-lymphocyte non-coding genetic variants in Type 1 Diabetes.

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