期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：26
页码：16893-16898
DOI：10.1073/pnas.252638199
语种：English
出版社：The National Academy of Sciences of the United States of America
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.
