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A Boolean approach for novel hypoxia-related gene discovery

Hypoxia plays a major role in the etiology and pathogenesis of most of the leading causes of morbidity and mortality, whether cardiovascular diseases, cancer, respiratory diseases or stroke. Despite active research on hypoxia-signaling pathways, the understanding of regulatory mechanisms, especially...

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Detalles Bibliográficos
Autores principales: Stobdan, Tsering, Sahoo, Debashis, Haddad, Gabriel G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409593/
https://www.ncbi.nlm.nih.gov/pubmed/36006949
http://dx.doi.org/10.1371/journal.pone.0273524
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author Stobdan, Tsering
Sahoo, Debashis
Haddad, Gabriel G.
author_facet Stobdan, Tsering
Sahoo, Debashis
Haddad, Gabriel G.
author_sort Stobdan, Tsering
collection PubMed
description Hypoxia plays a major role in the etiology and pathogenesis of most of the leading causes of morbidity and mortality, whether cardiovascular diseases, cancer, respiratory diseases or stroke. Despite active research on hypoxia-signaling pathways, the understanding of regulatory mechanisms, especially in specific tissues, still remain elusive. With the accessibility of thousands of potentially diverse genomic datasets, computational methods are utilized to generate new hypotheses. Here we utilized Boolean implication relationship, a powerful method to probe symmetrically and asymmetrically related genes, to identify novel hypoxia related genes. We used a well-known hypoxia-responsive gene, VEGFA, with very large human expression datasets (n = 25,955) to identify novel hypoxia-responsive candidate gene/s. Further, we utilized in-vitro analysis using human endothelial cells exposed to 1% O(2) environment for 2, 8, 24 and 48 hours to validate top candidate genes. Out of the top candidate genes (n = 19), 84% genes were previously reported as hypoxia related, validating our results. However, we identified FAM114A1 as a novel candidate gene significantly upregulated in the endothelial cells at 8, 24 and 48 hours of 1% O(2) environment. Additional evidence, particularly the localization of intronic miRNA and numerous HREs further support and strengthen our finding. Current results on FAM114A1 provide an example demonstrating the utility of powerful computational methods, like Boolean implications, in playing a major role in hypothesis building and discovery.
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spelling pubmed-94095932022-08-26 A Boolean approach for novel hypoxia-related gene discovery Stobdan, Tsering Sahoo, Debashis Haddad, Gabriel G. PLoS One Research Article Hypoxia plays a major role in the etiology and pathogenesis of most of the leading causes of morbidity and mortality, whether cardiovascular diseases, cancer, respiratory diseases or stroke. Despite active research on hypoxia-signaling pathways, the understanding of regulatory mechanisms, especially in specific tissues, still remain elusive. With the accessibility of thousands of potentially diverse genomic datasets, computational methods are utilized to generate new hypotheses. Here we utilized Boolean implication relationship, a powerful method to probe symmetrically and asymmetrically related genes, to identify novel hypoxia related genes. We used a well-known hypoxia-responsive gene, VEGFA, with very large human expression datasets (n = 25,955) to identify novel hypoxia-responsive candidate gene/s. Further, we utilized in-vitro analysis using human endothelial cells exposed to 1% O(2) environment for 2, 8, 24 and 48 hours to validate top candidate genes. Out of the top candidate genes (n = 19), 84% genes were previously reported as hypoxia related, validating our results. However, we identified FAM114A1 as a novel candidate gene significantly upregulated in the endothelial cells at 8, 24 and 48 hours of 1% O(2) environment. Additional evidence, particularly the localization of intronic miRNA and numerous HREs further support and strengthen our finding. Current results on FAM114A1 provide an example demonstrating the utility of powerful computational methods, like Boolean implications, in playing a major role in hypothesis building and discovery. Public Library of Science 2022-08-25 /pmc/articles/PMC9409593/ /pubmed/36006949 http://dx.doi.org/10.1371/journal.pone.0273524 Text en © 2022 Stobdan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Stobdan, Tsering
Sahoo, Debashis
Haddad, Gabriel G.
A Boolean approach for novel hypoxia-related gene discovery
title A Boolean approach for novel hypoxia-related gene discovery
title_full A Boolean approach for novel hypoxia-related gene discovery
title_fullStr A Boolean approach for novel hypoxia-related gene discovery
title_full_unstemmed A Boolean approach for novel hypoxia-related gene discovery
title_short A Boolean approach for novel hypoxia-related gene discovery
title_sort boolean approach for novel hypoxia-related gene discovery
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409593/
https://www.ncbi.nlm.nih.gov/pubmed/36006949
http://dx.doi.org/10.1371/journal.pone.0273524
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