Identification of chemogenomic features from drug-target interaction networks using interpretable classifiers

作者：Tabei Yasuo; Pauwels Edouard; Stoven Veronique; Takemoto Kazuhiro; Yamanishi Yoshihiro^*

来源：Bioinformatics, 2012, 28(18): I487-I494.

DOI：10.1093/bioinformatics/bts412

Motivation: Drug effects are mainly caused by the interactions between drug molecules and their target proteins including primary targets and off-targets. Identification of the molecular mechanisms behind overall drug-target interactions is crucial in the drug design %26lt;br%26gt;Results: We develop a classifier-based approach to identify chemogenomic features (the underlying associations between drug chemical substructures and protein domains) that are involved in drug-target interaction networks. We propose a novel algorithm for extracting informative chemogenomic features by using L-1 regularized classifiers over the tensor product space of possible drug-target pairs. It is shown that the proposed method can extract a very limited number of chemogenomic features without loosing the performance of predicting drug-target interactions and the extracted features are biologically meaningful. The extracted substructure-domain association network enables us to suggest ligand chemical fragments specific for each protein domain and ligand core substructures important for a wide range of protein families.

• 出版日期2012-9-15