Drug target prediction using adverse event report systems: a pharmacogenomic approach

作者：Takarabe Masataka; Kotera Masaaki; Nishimura Yosuke; Goto Susumu; Yamanishi Yoshihiro^*

来源：Bioinformatics, 2012, 28(18): I611-I618.

DOI：10.1093/bioinformatics/bts413

Motivation: Unexpected drug activities derived from off-targets are usually undesired and harmful; however, they can occasionally be beneficial for different therapeutic indications. There are many uncharacterized drugs whose target proteins (including the primary target and off-targets) remain unknown. The identification of all potential drug targets has become an important issue in drug repositioning to reuse known drugs for new therapeutic indications. %26lt;br%26gt;Results: We defined pharmacological similarity for all possible drugs using the US Food and Drug Administration%26apos;s (FDA%26apos;s) adverse event reporting system (AERS) and developed a new method to predict unknown drug-target interactions on a large scale from the integration of pharmacological similarity of drugs and genomic sequence similarity of target proteins in the framework of a pharmacogenomic approach. The proposed method was applicable to a large number of drugs and it was useful especially for predicting unknown drug-target interactions that could not be expected from drug chemical structures. We made a comprehensive prediction for potential off-targets of 1874 drugs with known targets and potential target profiles of 2519 drugs without known targets, which suggests many potential drug-target interactions that were not predicted by previous chemogenomic or pharmacogenomic approaches.

• 出版日期2012-9-15