A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs

In recent years, the increase in awareness of antimicrobial resistance together with the societal demand of healthier meat products have driven attention to health-related traits in livestock production. Previous studies have reported medium to high heritabilities for these traits and described geno...

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Autores principales:	Daniel Crespo-Piazuelo, Yuliaxis Ramayo-Caldas, Olga González-Rodríguez, Mariam Pascual, Raquel Quintanilla, Maria Ballester
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	immunocompetence pig gene networks transcription factors systems biology candidate genes Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/e8dedb6e4095409bb5c7a8b7f55c9ed4
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spelling	oai:doaj.org-article:e8dedb6e4095409bb5c7a8b7f55c9ed42021-12-01T08:02:52ZA Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs1664-322410.3389/fimmu.2021.784978https://doaj.org/article/e8dedb6e4095409bb5c7a8b7f55c9ed42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.784978/fullhttps://doaj.org/toc/1664-3224In recent years, the increase in awareness of antimicrobial resistance together with the societal demand of healthier meat products have driven attention to health-related traits in livestock production. Previous studies have reported medium to high heritabilities for these traits and described genomic regions associated with them. Despite its genetic component, health- and immunity-related traits are complex and its study by association analysis with genomic markers may be missing some information. To analyse multiple phenotypes and gene-by-gene interactions, systems biology approaches, such as the association weight matrix (AWM), allows combining genome wide association study results with network inference algorithms. The present study aimed to identify gene networks, key regulators and candidate genes associated to immunocompetence in pigs by integrating multiple health-related traits, enriched for innate immune phenotypes, using the AWM approach. The co-association network analysis unveiled a network comprised of 3,636 nodes (genes) and 451,407 edges (interactions), including a total of 246 regulators. From these, five genes (ARNT2, BRMS1L, MED12L, SUPT3H and TRIM25) were selected as key regulators as they were associated with the maximum number of genes with the minimum overlapping (1,827 genes in total). The five regulators were involved in pathways related to immunity such as lymphocyte differentiation and activation, platelet activation and degranulation, megakaryocyte differentiation, FcγR-mediated phagocytosis and response to nitric oxide, among others, but also in immunometabolism. Furthermore, we identified genes co-associated with the key regulators previously reported as candidate genes (e.g., ANGPT1, CD4, CD36, DOCK1, PDE4B, PRKCE, PTPRC and SH2B3) for immunity traits in humans and pigs, but also new candidate ones (e.g., ACSL3, CXADR, HBB, MMP12, PTPN6, WLS) that were not previously described. The co-association analysis revealed new regulators associated with health-related traits in pigs. This approach also identified gene-by-gene interactions and candidate genes involved in pathways related to cell fate and metabolic and immune functions. Our results shed new light in the regulatory mechanisms involved in pig immunity and reinforce the use of the pig as biomedical model.Daniel Crespo-PiazueloYuliaxis Ramayo-CaldasOlga González-RodríguezMariam PascualRaquel QuintanillaMaria BallesterFrontiers Media S.A.articleimmunocompetencepiggene networkstranscription factorssystems biologycandidate genesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immunocompetence pig gene networks transcription factors systems biology candidate genes Immunologic diseases. Allergy RC581-607
spellingShingle	immunocompetence pig gene networks transcription factors systems biology candidate genes Immunologic diseases. Allergy RC581-607 Daniel Crespo-Piazuelo Yuliaxis Ramayo-Caldas Olga González-Rodríguez Mariam Pascual Raquel Quintanilla Maria Ballester A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs
description	In recent years, the increase in awareness of antimicrobial resistance together with the societal demand of healthier meat products have driven attention to health-related traits in livestock production. Previous studies have reported medium to high heritabilities for these traits and described genomic regions associated with them. Despite its genetic component, health- and immunity-related traits are complex and its study by association analysis with genomic markers may be missing some information. To analyse multiple phenotypes and gene-by-gene interactions, systems biology approaches, such as the association weight matrix (AWM), allows combining genome wide association study results with network inference algorithms. The present study aimed to identify gene networks, key regulators and candidate genes associated to immunocompetence in pigs by integrating multiple health-related traits, enriched for innate immune phenotypes, using the AWM approach. The co-association network analysis unveiled a network comprised of 3,636 nodes (genes) and 451,407 edges (interactions), including a total of 246 regulators. From these, five genes (ARNT2, BRMS1L, MED12L, SUPT3H and TRIM25) were selected as key regulators as they were associated with the maximum number of genes with the minimum overlapping (1,827 genes in total). The five regulators were involved in pathways related to immunity such as lymphocyte differentiation and activation, platelet activation and degranulation, megakaryocyte differentiation, FcγR-mediated phagocytosis and response to nitric oxide, among others, but also in immunometabolism. Furthermore, we identified genes co-associated with the key regulators previously reported as candidate genes (e.g., ANGPT1, CD4, CD36, DOCK1, PDE4B, PRKCE, PTPRC and SH2B3) for immunity traits in humans and pigs, but also new candidate ones (e.g., ACSL3, CXADR, HBB, MMP12, PTPN6, WLS) that were not previously described. The co-association analysis revealed new regulators associated with health-related traits in pigs. This approach also identified gene-by-gene interactions and candidate genes involved in pathways related to cell fate and metabolic and immune functions. Our results shed new light in the regulatory mechanisms involved in pig immunity and reinforce the use of the pig as biomedical model.
format	article
author	Daniel Crespo-Piazuelo Yuliaxis Ramayo-Caldas Olga González-Rodríguez Mariam Pascual Raquel Quintanilla Maria Ballester
author_facet	Daniel Crespo-Piazuelo Yuliaxis Ramayo-Caldas Olga González-Rodríguez Mariam Pascual Raquel Quintanilla Maria Ballester
author_sort	Daniel Crespo-Piazuelo
title	A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs
title_short	A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs
title_full	A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs
title_fullStr	A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs
title_full_unstemmed	A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs
title_sort	co-association network analysis reveals putative regulators for health-related traits in pigs
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/e8dedb6e4095409bb5c7a8b7f55c9ed4
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A Co-Association Network Analysis Reveals Putative Regulators for Health-Related Traits in Pigs

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