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Inference of a Transcriptional Network Involved in Chemical Inhibition of Estrogen Synthesis in Fathead Minnow
Citation:
HABIB, T., DAN VILLENEUVE, D. MARTINOVIC, Y. DENG, G. T. ANKLEY, E. PERKINS, AND N. G. REYERO. Inference of a Transcriptional Network Involved in Chemical Inhibition of Estrogen Synthesis in Fathead Minnow. Presented at 6th Annual Conference of the Midsouth Computational Biology and Bioinformatics Society, MCBIOS 2009, Starkville, MS, February 20 - 21, 2009.
Impact/Purpose:
A variety of chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis. We examined the responses of female fathead minnows (Pimephales promelas) to a model aromatase inhibitor, fadrozole, using transcriptional network inference.
Description:
A variety of chemicals in the environment have the potential to inhibit aromatase, an enzyme critical to estrogen synthesis. We examined the responses of female fathead minnows (Pimephales promelas) to a model aromatase inhibitor, fadrozole, using transcriptional network inference. Fish were exposed for 8 days to 0, 3, or 30μg/L fadrozol and then held in clean water for 8 extra days. We analyzed ex vivo steroid production, plasma steroid levels, and plasma vitellogenin concentrations in the ovary, as well as gene expression using 15,000 probe microarrays. The top 200 significantly changed genes based upon 2-fold change and P< 0.01 were taken for network modeling. A graphical Gaussian model was used to generate a network containing 91,800 interactions among 136 genes. The top 500 edges were queried to find a possible biological network, biochemical pathways, sub-networks and the network topologies. The network was densely organized with an average network node connectivity of 4.2. Overall, the network observed a power-law distribution and sub-networks were scale free. Aromatase was a highly connected gene in a sub-network along with the genes VIM, HOMER1, KRT15, and ICLP2. Many of the sub-networks were involved in fatty acid metabolism, gamma-hexachlorocyclohexane degradation, and phospholipase activating pathways.