| The TAO-Gen Algorithm for Identifying Gene Interaction Networks with Application to SOS Repair in E. coli Takeharu Yamanaka, Hiroyoshi Toyoshiba, Hideko Sone, Frederick M. Parham, and Christopher J. Portier Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA Abstract
One major unresolved issue in the analysis of gene expression data is the identification and quantification of gene regulatory networks. Several methods have been proposed for identifying gene regulatory networks, but these methods predominantly focus on the use of multiple pairwise comparisons to identify the network structure. In this article, we describe a method for analyzing gene expression data to determine a regulatory structure consistent with an observed set of expression profiles. Unlike other methods this method goes beyond pairwise evaluations by using likelihood-based statistical methods to obtain the network that is most consistent with the complete data set. The proposed algorithm performs accurately for moderate-sized networks with most errors being minor additions of linkages. However, the analysis also indicates that sample sizes may need to be increased to uniquely identify even moderate-sized networks. The method is used to evaluate interactions between genes in the SOS signaling pathway in Escherichia coli using gene expression data where each gene in the network is over-expressed using plasmids inserts. Key words: gene networks, microarray, Bayesian model selection, SOS repair, toxicogenomics. Environ Health Perspect 112: 1614-1621 (2004) . doi:10.1289/txg.7105 available via http://dx.doi.org/ [Online 21 July 2004]
Address correspondence to C.J. Portier, Laboratory of Computational Biology and Risk Analysis, NIEHS, P.O. Box 12233, MD A3-06, 111 Alexander Dr., Research Triangle Park, NC 27709. Telephone: (919) 541-3802. Fax: (919) 541-3647. E-mail: portier@niehs.nih.gov We would like to thank T. Darden, S. Roel, and N. Walker for helpful comments and advices. The authors declare they have no competing financial interests. Received 19 March 2004 ; accepted 21 July 2004.
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