Prediction of drug-target interaction networks from the integration of chemical and genomic spaces

Yoshihiro Yamanishi, Michihiro Araki, Alex Gutteridge, Wataru Honda, Minoru Kanehisa

    Research output: Contribution to journalArticlepeer-review

    563 Citations (Scopus)


    Motivation: The identification of interactions between drugs and target proteins is a key area in genomic drug discovery. Therefore, there is a strong incentive to develop new methods capable of detecting these potential drug-target interactions efficiently. Results: In this article, we characterize four classes of drug-target interaction networks in humans involving enzymes, ion channels, G-protein-coupled receptors (GPCRs) and nuclear receptors, and reveal significant correlations between drug structure similarity, target sequence similarity and the drug-target interaction network topology. We then develop new statistical methods to predict unknown drug-target interaction networks from chemical structure and genomic sequence information simultaneously on a large scale. The originality of the proposed method lies in the formalization of the drug-target interaction inference as a supervised learning problem for a bipartite graph, the lack of need for 3D structure information of the target proteins, and in the integration of chemical and genomic spaces into a unified space that we call 'pharmacological space'. In the results, we demonstrate the usefulness of our proposed method for the prediction of the four classes of drug-target interaction networks. Our comprehensively predicted drug-target interaction networks enable us to suggest many potential drug-target interactions and to increase research productivity toward genomic drug discovery.

    Original languageEnglish
    Pages (from-to)i232-i240
    Issue number13
    Publication statusPublished - Jul 2008

    All Science Journal Classification (ASJC) codes

    • Statistics and Probability
    • Biochemistry
    • Molecular Biology
    • Computer Science Applications
    • Computational Theory and Mathematics
    • Computational Mathematics

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