Tissue-specific functional networks for prioritizing phenotype and disease genes.

Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue...

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Autores principales:	Yuanfang Guan, Dmitriy Gorenshteyn, Margit Burmeister, Aaron K Wong, John C Schimenti, Mary Ann Handel, Carol J Bult, Matthew A Hibbs, Olga G Troyanskaya
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/cd24d7aa560e4a8ab919491b64fa491f
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spelling	oai:doaj.org-article:cd24d7aa560e4a8ab919491b64fa491f2021-11-18T05:50:57ZTissue-specific functional networks for prioritizing phenotype and disease genes.1553-734X1553-735810.1371/journal.pcbi.1002694https://doaj.org/article/cd24d7aa560e4a8ab919491b64fa491f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028291/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.Yuanfang GuanDmitriy GorenshteynMargit BurmeisterAaron K WongJohn C SchimentiMary Ann HandelCarol J BultMatthew A HibbsOlga G TroyanskayaPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 8, Iss 9, p e1002694 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Yuanfang Guan Dmitriy Gorenshteyn Margit Burmeister Aaron K Wong John C Schimenti Mary Ann Handel Carol J Bult Matthew A Hibbs Olga G Troyanskaya Tissue-specific functional networks for prioritizing phenotype and disease genes.
description	Integrated analyses of functional genomics data have enormous potential for identifying phenotype-associated genes. Tissue-specificity is an important aspect of many genetic diseases, reflecting the potentially different roles of proteins and pathways in diverse cell lineages. Accounting for tissue specificity in global integration of functional genomics data is challenging, as "functionality" and "functional relationships" are often not resolved for specific tissue types. We address this challenge by generating tissue-specific functional networks, which can effectively represent the diversity of protein function for more accurate identification of phenotype-associated genes in the laboratory mouse. Specifically, we created 107 tissue-specific functional relationship networks through integration of genomic data utilizing knowledge of tissue-specific gene expression patterns. Cross-network comparison revealed significantly changed genes enriched for functions related to specific tissue development. We then utilized these tissue-specific networks to predict genes associated with different phenotypes. Our results demonstrate that prediction performance is significantly improved through using the tissue-specific networks as compared to the global functional network. We used a testis-specific functional relationship network to predict genes associated with male fertility and spermatogenesis phenotypes, and experimentally confirmed one top prediction, Mbyl1. We then focused on a less-common genetic disease, ataxia, and identified candidates uniquely predicted by the cerebellum network, which are supported by both literature and experimental evidence. Our systems-level, tissue-specific scheme advances over traditional global integration and analyses and establishes a prototype to address the tissue-specific effects of genetic perturbations, diseases and drugs.
format	article
author	Yuanfang Guan Dmitriy Gorenshteyn Margit Burmeister Aaron K Wong John C Schimenti Mary Ann Handel Carol J Bult Matthew A Hibbs Olga G Troyanskaya
author_facet	Yuanfang Guan Dmitriy Gorenshteyn Margit Burmeister Aaron K Wong John C Schimenti Mary Ann Handel Carol J Bult Matthew A Hibbs Olga G Troyanskaya
author_sort	Yuanfang Guan
title	Tissue-specific functional networks for prioritizing phenotype and disease genes.
title_short	Tissue-specific functional networks for prioritizing phenotype and disease genes.
title_full	Tissue-specific functional networks for prioritizing phenotype and disease genes.
title_fullStr	Tissue-specific functional networks for prioritizing phenotype and disease genes.
title_full_unstemmed	Tissue-specific functional networks for prioritizing phenotype and disease genes.
title_sort	tissue-specific functional networks for prioritizing phenotype and disease genes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/cd24d7aa560e4a8ab919491b64fa491f
work_keys_str_mv	AT yuanfangguan tissuespecificfunctionalnetworksforprioritizingphenotypeanddiseasegenes AT dmitriygorenshteyn tissuespecificfunctionalnetworksforprioritizingphenotypeanddiseasegenes AT margitburmeister tissuespecificfunctionalnetworksforprioritizingphenotypeanddiseasegenes AT aaronkwong tissuespecificfunctionalnetworksforprioritizingphenotypeanddiseasegenes AT johncschimenti tissuespecificfunctionalnetworksforprioritizingphenotypeanddiseasegenes AT maryannhandel tissuespecificfunctionalnetworksforprioritizingphenotypeanddiseasegenes AT caroljbult tissuespecificfunctionalnetworksforprioritizingphenotypeanddiseasegenes AT matthewahibbs tissuespecificfunctionalnetworksforprioritizingphenotypeanddiseasegenes AT olgagtroyanskaya tissuespecificfunctionalnetworksforprioritizingphenotypeanddiseasegenes
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Tissue-specific functional networks for prioritizing phenotype and disease genes.

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