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Nucleic Acids Research 2005 33(15):4828-4837; doi:10.1093/nar/gki793
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Published online 26 August 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

Identifying cooperative transcriptional regulations using protein–protein interactions

Nobuyoshi Nagamine, Yuji Kawada and Yasubumi Sakakibara*

Department of Biosciences and Informatics, Keio University 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan

*To whom correspondence should be addressed. Tel/Fax: +81 45 566 1791; Email: yasu{at}bio.keio.ac.jp

Received April 6, 2005. Revised July 2, 2005. Accepted August 9, 2005.

Cooperative transcriptional activations among multiple transcription factors (TFs) are important to understand the mechanisms of complex transcriptional regulations in eukaryotes. Previous studies have attempted to find cooperative TFs based on gene expression data with gene expression profiles as a measure of similarity of gene regulations. In this paper, we use protein–protein interaction data to infer synergistic binding of cooperative TFs. Our fundamental idea is based on the assumption that genes contributing to a similar biological process are regulated under the same control mechanism. First, the protein–protein interaction networks are used to calculate the similarity of biological processes among genes. Second, we integrate this similarity and the chromatin immuno-precipitation data to identify cooperative TFs. Our computational experiments in yeast show that predictions made by our method have successfully identified eight pairs of cooperative TFs that have literature evidences but could not be identified by the previous method. Further, 12 new possible pairs have been inferred and we have examined the biological relevances for them. However, since a typical problem using protein–protein interaction data is that many false-positive data are contained, we propose a method combining various biological data to increase the prediction accuracy.


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