Knowledge-guided gene ranking by coordinative component analysis

<p>Abstract</p> <p>Background</p> <p>In cancer, gene networks and pathways often exhibit dynamic behavior, particularly during the process of carcinogenesis. Thus, it is important to prioritize those genes that are strongly associated with the functionality of a network...

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Main Authors: Hoffman Eric P, Zhan Ming, Wang Yue, Li Huai, Xuan Jianhua, Wang Chen, Clarke Robert
Format: Article
Language:English
Published: BMC 2010-03-01
Series:BMC Bioinformatics
Online Access:http://www.biomedcentral.com/1471-2105/11/162
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author Hoffman Eric P
Zhan Ming
Wang Yue
Li Huai
Xuan Jianhua
Wang Chen
Clarke Robert
author_facet Hoffman Eric P
Zhan Ming
Wang Yue
Li Huai
Xuan Jianhua
Wang Chen
Clarke Robert
author_sort Hoffman Eric P
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>In cancer, gene networks and pathways often exhibit dynamic behavior, particularly during the process of carcinogenesis. Thus, it is important to prioritize those genes that are strongly associated with the functionality of a network. Traditional statistical methods are often inept to identify biologically relevant member genes, motivating researchers to incorporate biological knowledge into gene ranking methods. However, current integration strategies are often heuristic and fail to incorporate fully the true interplay between biological knowledge and gene expression data.</p> <p>Results</p> <p>To improve knowledge-guided gene ranking, we propose a novel method called coordinative component analysis (COCA) in this paper. COCA explicitly captures those genes within a specific biological context that are likely to be expressed in a coordinative manner. Formulated as an optimization problem to maximize the coordinative effort, COCA is designed to first extract the coordinative components based on a partial guidance from knowledge genes and then rank the genes according to their participation strengths. An embedded bootstrapping procedure is implemented to improve statistical robustness of the solutions. COCA was initially tested on simulation data and then on published gene expression microarray data to demonstrate its improved performance as compared to traditional statistical methods. Finally, the COCA approach has been applied to stem cell data to identify biologically relevant genes in signaling pathways. As a result, the COCA approach uncovers novel pathway members that may shed light into the pathway deregulation in cancers.</p> <p>Conclusion</p> <p>We have developed a new integrative strategy to combine biological knowledge and microarray data for gene ranking. The method utilizes knowledge genes for a guidance to first extract coordinative components, and then rank the genes according to their contribution related to a network or pathway. The experimental results show that such a knowledge-guided strategy can provide context-specific gene ranking with an improved performance in pathway member identification.</p>
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spelling doaj.art-f7e561e04324465f9c1978f72a6deca82022-12-22T03:26:13ZengBMCBMC Bioinformatics1471-21052010-03-0111116210.1186/1471-2105-11-162Knowledge-guided gene ranking by coordinative component analysisHoffman Eric PZhan MingWang YueLi HuaiXuan JianhuaWang ChenClarke Robert<p>Abstract</p> <p>Background</p> <p>In cancer, gene networks and pathways often exhibit dynamic behavior, particularly during the process of carcinogenesis. Thus, it is important to prioritize those genes that are strongly associated with the functionality of a network. Traditional statistical methods are often inept to identify biologically relevant member genes, motivating researchers to incorporate biological knowledge into gene ranking methods. However, current integration strategies are often heuristic and fail to incorporate fully the true interplay between biological knowledge and gene expression data.</p> <p>Results</p> <p>To improve knowledge-guided gene ranking, we propose a novel method called coordinative component analysis (COCA) in this paper. COCA explicitly captures those genes within a specific biological context that are likely to be expressed in a coordinative manner. Formulated as an optimization problem to maximize the coordinative effort, COCA is designed to first extract the coordinative components based on a partial guidance from knowledge genes and then rank the genes according to their participation strengths. An embedded bootstrapping procedure is implemented to improve statistical robustness of the solutions. COCA was initially tested on simulation data and then on published gene expression microarray data to demonstrate its improved performance as compared to traditional statistical methods. Finally, the COCA approach has been applied to stem cell data to identify biologically relevant genes in signaling pathways. As a result, the COCA approach uncovers novel pathway members that may shed light into the pathway deregulation in cancers.</p> <p>Conclusion</p> <p>We have developed a new integrative strategy to combine biological knowledge and microarray data for gene ranking. The method utilizes knowledge genes for a guidance to first extract coordinative components, and then rank the genes according to their contribution related to a network or pathway. The experimental results show that such a knowledge-guided strategy can provide context-specific gene ranking with an improved performance in pathway member identification.</p>http://www.biomedcentral.com/1471-2105/11/162
spellingShingle Hoffman Eric P
Zhan Ming
Wang Yue
Li Huai
Xuan Jianhua
Wang Chen
Clarke Robert
Knowledge-guided gene ranking by coordinative component analysis
BMC Bioinformatics
title Knowledge-guided gene ranking by coordinative component analysis
title_full Knowledge-guided gene ranking by coordinative component analysis
title_fullStr Knowledge-guided gene ranking by coordinative component analysis
title_full_unstemmed Knowledge-guided gene ranking by coordinative component analysis
title_short Knowledge-guided gene ranking by coordinative component analysis
title_sort knowledge guided gene ranking by coordinative component analysis
url http://www.biomedcentral.com/1471-2105/11/162
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AT zhanming knowledgeguidedgenerankingbycoordinativecomponentanalysis
AT wangyue knowledgeguidedgenerankingbycoordinativecomponentanalysis
AT lihuai knowledgeguidedgenerankingbycoordinativecomponentanalysis
AT xuanjianhua knowledgeguidedgenerankingbycoordinativecomponentanalysis
AT wangchen knowledgeguidedgenerankingbycoordinativecomponentanalysis
AT clarkerobert knowledgeguidedgenerankingbycoordinativecomponentanalysis