A systematic approach to reconstructing transcription networks in Saccharomyces cerevisiae

被引:70
作者
Wang, W
Cherry, JM
Botstein, D [1 ]
Li, H
机构
[1] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
[2] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
关键词
D O I
10.1073/pnas.252638199
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Decomposing regulatory networks into functional modules is a first step toward deciphering the logical structure of complex networks. We propose a systematic approach to reconstructing transcription modules (defined by a transcription factor and its target genes) and identifying conditions/perturbations under which a particular transcription module is activated/deactivated. Our approach integrates information from regulatory sequences, genome-wide mRNA expression data, and functional annotation. We systematically analyzed gene expression profiling experiments in which the yeast cell was subjected to various environmental or genetic perturbations. We were able to construct transcription modules with high specificity and sensitivity for many transcription factors, and predict the activation of these modules under anticipated as well as unexpected conditions. These findings generate testable hypotheses when combined with existing knowledge on signaling pathways and protein-protein interactions. Correlating the activation of a module to a specific perturbation predicts links in the cell's regulatory networks, and examining coactivated modules suggests specific instances of crosstalk between regulatory pathways.
引用
收藏
页码:16893 / 16898
页数:6
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