| Gene Interaction Network Suggests Dioxin Induces a Significant Linkage between Aryl Hydrocarbon Receptor and Retinoic Acid Receptor Beta Hiroyoshi Toyoshiba, Takeharu Yamanaka, Hideko Sone, Frederick M. Parham,
Nigel J. Walker, Jeanelle Martinez, and Christopher J. Portier
Laboratory of Computational Biology and Risk Analysis, National Institute of
Environmental Health Sciences, Research Triangle Park, North Carolina, USA Abstract
Gene expression arrays (gene chips) have enabled researchers to roughly quantify the level of mRNA expression for a large number of genes in a single sample. Several methods have been developed for the analysis of gene array data including clustering, outlier detection, and correlation studies. Most of these analyses are aimed at a qualitative identification of what is different between two samples and/or the relationship between two genes. We propose a quantitative, statistically sound methodology for the analysis of gene regulatory networks using gene expression data sets. The method is based on Bayesian networks for direct quantification of gene expression networks. Using the gene expression changes in HPL1A lung airway epithelial cells after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin at levels of 0.1, 1.0, and 10.0 nM for 24 hr, a gene expression network was hypothesized and analyzed. The method clearly demonstrates support for the assumed network and the hypothesis linking the usual dioxin expression changes to the retinoic acid receptor system. Simulation studies demonstrated the method works well, even for small samples. Key words: Bayesian networks, dioxin, gene regulatory networks, Markov chain Monte Carlo, retinoic acid receptor, risk assessment, systems biology, toxicogenomics. Environ Health Perspect 112:1217-1224 (2004) . doi:10.1289/txg.7020 available via http://dx.doi.org/ [Online 23 June 2004]
Address correspondence to C.J. Portier, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27709. Telephone: (919) 541-3802. Fax: (919) 541-3647. E-mail: portier@niehs.nih.gov The authors declare they have no competing financial interests. Received 10 February 2004 ; accepted 23 June 2004.
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