Allele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.

The study of systems genetics is changing the way the genetic and molecular basis of phenotypic variation, such as disease susceptibility and drug response, is being analyzed. Moreover, systems genetics aids in the translation of insights from systems biology into genetics. The use of systems geneti...

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Autores principales:	Fan Zhang, Bo Gao, Liangde Xu, Chunquan Li, Dapeng Hao, Shaojun Zhang, Meng Zhou, Fei Su, Xi Chen, Hui Zhi, Xia Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/979d96028c1c4864bf7091e5a7173b95
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spelling	oai:doaj.org-article:979d96028c1c4864bf7091e5a7173b952021-11-18T08:02:36ZAllele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.1932-620310.1371/journal.pone.0053581https://doaj.org/article/979d96028c1c4864bf7091e5a7173b952013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23308257/?tool=EBIhttps://doaj.org/toc/1932-6203The study of systems genetics is changing the way the genetic and molecular basis of phenotypic variation, such as disease susceptibility and drug response, is being analyzed. Moreover, systems genetics aids in the translation of insights from systems biology into genetics. The use of systems genetics enables greater attention to be focused on the potential impact of genetic perturbations on the molecular states of networks that in turn affects complex traits. In this study, we developed models to detect allele-specific perturbations on interactions, in which a genetic locus with alternative alleles exerted a differing influence on an interaction. We utilized the models to investigate the dynamic behavior of an integrated molecular network undergoing genetic perturbations in yeast. Our results revealed the complexity of regulatory relationships between genetic loci and networks, in which different genetic loci perturb specific network modules. In addition, significant within-module functional coherence was found. We then used the network perturbation model to elucidate the underlying molecular mechanisms of individual differences in response to 100 diverse small molecule drugs. As a result, we identified sub-networks in the integrated network that responded to variations in DNA associated with response to diverse compounds and were significantly enriched for known drug targets. Literature mining results provided strong independent evidence for the effectiveness of these genetic perturbing networks in the elucidation of small-molecule responses in yeast.Fan ZhangBo GaoLiangde XuChunquan LiDapeng HaoShaojun ZhangMeng ZhouFei SuXi ChenHui ZhiXia LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53581 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fan Zhang Bo Gao Liangde Xu Chunquan Li Dapeng Hao Shaojun Zhang Meng Zhou Fei Su Xi Chen Hui Zhi Xia Li Allele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.
description	The study of systems genetics is changing the way the genetic and molecular basis of phenotypic variation, such as disease susceptibility and drug response, is being analyzed. Moreover, systems genetics aids in the translation of insights from systems biology into genetics. The use of systems genetics enables greater attention to be focused on the potential impact of genetic perturbations on the molecular states of networks that in turn affects complex traits. In this study, we developed models to detect allele-specific perturbations on interactions, in which a genetic locus with alternative alleles exerted a differing influence on an interaction. We utilized the models to investigate the dynamic behavior of an integrated molecular network undergoing genetic perturbations in yeast. Our results revealed the complexity of regulatory relationships between genetic loci and networks, in which different genetic loci perturb specific network modules. In addition, significant within-module functional coherence was found. We then used the network perturbation model to elucidate the underlying molecular mechanisms of individual differences in response to 100 diverse small molecule drugs. As a result, we identified sub-networks in the integrated network that responded to variations in DNA associated with response to diverse compounds and were significantly enriched for known drug targets. Literature mining results provided strong independent evidence for the effectiveness of these genetic perturbing networks in the elucidation of small-molecule responses in yeast.
format	article
author	Fan Zhang Bo Gao Liangde Xu Chunquan Li Dapeng Hao Shaojun Zhang Meng Zhou Fei Su Xi Chen Hui Zhi Xia Li
author_facet	Fan Zhang Bo Gao Liangde Xu Chunquan Li Dapeng Hao Shaojun Zhang Meng Zhou Fei Su Xi Chen Hui Zhi Xia Li
author_sort	Fan Zhang
title	Allele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.
title_short	Allele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.
title_full	Allele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.
title_fullStr	Allele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.
title_full_unstemmed	Allele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.
title_sort	allele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/979d96028c1c4864bf7091e5a7173b95
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_version_	1718422618640482304

Allele-specific behavior of molecular networks: understanding small-molecule drug response in yeast.

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