Elucidating Polypharmacological Mechanisms of Polyphenols by Gene Module Profile Analysis
AbstractDue to the diverse medicinal effects, polyphenols are among the most intensively studied natural products. However, it is a great challenge to elucidate the polypharmacological mechanisms of polyphenols. To address this challenge, we establish a method for identifying multiple targets of chemical agents through analyzing the module profiles of gene expression upon chemical treatments. By using FABIA algorithm, we have performed a biclustering analysis of gene expression profiles derived from Connectivity Map (cMap), and clustered the profiles into 49 gene modules. This allowed us to define a 49 dimensional binary vector to characterize the gene module profiles, by which we can compare the expression profiles for each pair of chemical agents with Tanimoto coefficient. For the agent pairs with similar gene expression profiles, we can predict the target of one agent from the other. Drug target enrichment analysis indicated that this method is efficient to predict the multiple targets of chemical agents. By using this method, we identify 148 targets for 20 polyphenols derived from cMap. A large part of the targets are validated by experimental observations. The results show that the medicinal effects of polyphenols are far beyond their well-known antioxidant activities. This method is also applicable to dissect the polypharmacology of other natural products. View Full-Text
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Li, B.; Xiong, M.; Zhang, H.-Y. Elucidating Polypharmacological Mechanisms of Polyphenols by Gene Module Profile Analysis. Int. J. Mol. Sci. 2014, 15, 11245-11254.
Li B, Xiong M, Zhang H-Y. Elucidating Polypharmacological Mechanisms of Polyphenols by Gene Module Profile Analysis. International Journal of Molecular Sciences. 2014; 15(7):11245-11254.Chicago/Turabian Style
Li, Bin; Xiong, Min; Zhang, Hong-Yu. 2014. "Elucidating Polypharmacological Mechanisms of Polyphenols by Gene Module Profile Analysis." Int. J. Mol. Sci. 15, no. 7: 11245-11254.