Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver

Abstract Identifying individual genetic variation in drug metabolism pathways is of importance not only in livestock, but also in humans in order to provide the ultimate goal of giving the right drug at the right dose at the right time. Our objective was to identify individual genes and gene network...

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Autores principales:	Jeremy T. Howard, Melissa S. Ashwell, Ronald E. Baynes, James D. Brooks, James L. Yeatts, Christian Maltecca
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/23b23d05a48845e98efd4e4f76751f13
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spelling	oai:doaj.org-article:23b23d05a48845e98efd4e4f76751f132021-12-02T15:05:55ZGene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver10.1038/s41598-017-01526-52045-2322https://doaj.org/article/23b23d05a48845e98efd4e4f76751f132017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01526-5https://doaj.org/toc/2045-2322Abstract Identifying individual genetic variation in drug metabolism pathways is of importance not only in livestock, but also in humans in order to provide the ultimate goal of giving the right drug at the right dose at the right time. Our objective was to identify individual genes and gene networks involved in metabolizing fenbendazole (FBZ) and flunixin meglumine (FLU) in swine liver. The population consisted of female and castrated male pigs that were sired by boars represented by 4 breeds. Progeny were randomly placed into groups: no drug (UNT), FLU or FBZ administered. Liver transcriptome profiles from 60 animals with extreme (i.e. fast or slow drug metabolism) pharmacokinetic (PK) profiles were generated from RNA sequencing. Multiple cytochrome P450 (CYP1A1, CYP2A19 and CYP2C36) genes displayed different transcript levels across treated versus UNT. Weighted gene co-expression network analysis identified 5 and 3 modules of genes correlated with PK parameters and a portion of these were enriched for biological processes relevant to drug metabolism for FBZ and FLU, respectively. Genes within identified modules were shown to have a higher transcript level relationship (i.e. connectivity) in treated versus UNT animals. Investigation into the identified genes would allow for greater insight into FBZ and FLU metabolism.Jeremy T. HowardMelissa S. AshwellRonald E. BaynesJames D. BrooksJames L. YeattsChristian MalteccaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeremy T. Howard Melissa S. Ashwell Ronald E. Baynes James D. Brooks James L. Yeatts Christian Maltecca Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver
description	Abstract Identifying individual genetic variation in drug metabolism pathways is of importance not only in livestock, but also in humans in order to provide the ultimate goal of giving the right drug at the right dose at the right time. Our objective was to identify individual genes and gene networks involved in metabolizing fenbendazole (FBZ) and flunixin meglumine (FLU) in swine liver. The population consisted of female and castrated male pigs that were sired by boars represented by 4 breeds. Progeny were randomly placed into groups: no drug (UNT), FLU or FBZ administered. Liver transcriptome profiles from 60 animals with extreme (i.e. fast or slow drug metabolism) pharmacokinetic (PK) profiles were generated from RNA sequencing. Multiple cytochrome P450 (CYP1A1, CYP2A19 and CYP2C36) genes displayed different transcript levels across treated versus UNT. Weighted gene co-expression network analysis identified 5 and 3 modules of genes correlated with PK parameters and a portion of these were enriched for biological processes relevant to drug metabolism for FBZ and FLU, respectively. Genes within identified modules were shown to have a higher transcript level relationship (i.e. connectivity) in treated versus UNT animals. Investigation into the identified genes would allow for greater insight into FBZ and FLU metabolism.
format	article
author	Jeremy T. Howard Melissa S. Ashwell Ronald E. Baynes James D. Brooks James L. Yeatts Christian Maltecca
author_facet	Jeremy T. Howard Melissa S. Ashwell Ronald E. Baynes James D. Brooks James L. Yeatts Christian Maltecca
author_sort	Jeremy T. Howard
title	Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver
title_short	Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver
title_full	Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver
title_fullStr	Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver
title_full_unstemmed	Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver
title_sort	gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/23b23d05a48845e98efd4e4f76751f13
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Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver

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