Identifying changed protein-protein interactions in biological processes by gene coexpression analysis  

作　　者：ZHANG Ting ZHANG XueGong SUN ZhiRong 

机构地区：[1]Key Laboratory of Bioinformatics of Ministry of Education, State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China [2]Bioinformatics Division, TNLIST/Department of Automation, Tsinghua Un-iversi-ty, Beijing 100084, China

出　　处：《Chinese Science Bulletin》2010年第14期1396-1402,共7页

基　　金：supported in part by the National Natural Science Foundation of China (Grant Nos. 30770498, 30625012 and 60721003);the National High-Tech Research and Development Program of China (Grant No.2006AA020403);the National Basic Research Program of China (Grant No.2009CB918801)

摘　　要：The interaction strength between 2 proteins is not constant but variable under different conditions. For a given biological process, identification of protein-protein interactions (PPIs) undergoing dynamic change in interaction strength is highly valuable but never achieved before. In this work, we presented a computational approach to identify changed PPIs (cPPIs) on a global scale by analyzing the coexpression level of genes encoding the interacting protein pairs. This approach stemmed from the biological con-ception that the change of protein-protein interaction bore imprint at the gene coexpression level. We applied this method to identify cPPIs in cells treated with a cytokine TGFβ, as well as cPPIs in rheumatoid arthritis (RA) patients. The accuracy of identification was evaluated by comparing our results with data from the high-throughput experiment and literature mining. Our analysis demonstrated that this is a simple and effective method to infer cPPIs from a given set of PPIs or even from the whole interactome. Further analysis uncovered the biological functions of the cPPIs in RA patients, which included muscle contraction and antigen presentation. Our method could help to elucidate molecular mechanisms of dynamic biological processes.The interaction strength between 2 proteins is not constant but variable under different conditions. For a given biological process, identification of protein-protein interactions （PPIs） undergoing dynamic change in interaction strength is highly valuable but never achieved before. In this work, we presented a computational approach to identify changed PPIs （cPPIs） on a global scale by analyzing the coexpression level of genes encoding the interacting protein pairs. This approach stemmed from the biological conception that the change of protein-protein interaction bore imprint at the gene coexpression level. We applied this method to identify cPPIs in cells treated with a cytokine TGFβ, as well as cPPIs in rheumatoid arthritis （RA） patients. The accuracy of identification was evaluated by comparing our results with data from the high-throughput experiment and literature mining. Our analysis demonstrated that this is a simple and effective method to infer cPPIs from a given set of PPIs or even from the whole interactome. Further analysis uncovered the biological functions of the cPPIs in RA patients, which included muscle contraction and antigen presentation. Our method could help to elucidate molecular mechanisms of dynamic biological processes.

关 键 词：蛋白质相互作用 相互作用力 生物过程 表达分析 基因 识别 价格指数 转化生长因子 

分 类 号：Q78[生物学—分子生物学]