a regulatory network modeled from wild-type gene expression data guides functional predictions in caenorhabditis elegans development从野生型基因表达数据监管网络建模指南功能在秀丽隐杆线虫发展预测.pdfVIP

Stigler and Chamberlin BMC Systems Biology 2012, 6:77 /1752-0509/6/77 RESEARCH ARTICLE Open Access A regulatory network modeled from wild-type gene expression data guides functional predictions in Caenorhabditis elegans development Brandilyn Stigler1* and Helen M Chamberlin2 Abstract Background: Complex gene regulatory networks underlie many cellular and developmental processes. While a variety of experimental approaches can be used to discover how genes interact, few biological systems have been systematically evaluated to the extent required for an experimental definition of the underlying network. Therefore, the development of computational methods that can use limited experimental data to define and model a gene regulatory network would provide a useful tool to evaluate many important but incompletely understood biological processes. Such methods can assist in extracting all relevant information from data that are available, identify unexpected regulatory relationships and prioritize future experiments. Results: To facilitate the analysis of gene regulatory networks, we have developed a computational modeling pipeline method that complements traditional evaluation of experimental data. For a proof-of-concept example, we have focused on the gene regulatory network in the nematode C. elegans that mediates the developmental choice between mesodermal (muscle) and ectodermal (skin) cell fates in the embryonic C lineage. We have used gene expression data to build two models: a knowledge-driven model based on gene expression changes following gene perturbation experiments, and a data-driven mathematical model derived from time-course gene expression data recovered from wild-type animals. We show that both models can identify a rich set of network gene interactions. Importantly, the mathematical model built only from