Journal of Chemical Information and Modeling 2017-11-27

Differential Compound Prioritization via Bi-Directional Selectivity Push with Power

Junfeng Liu, Xia Ning

Index: 10.1021/acs.jcim.7b00552

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Abstract

Effective in silico compound prioritization is a critical step to identify promising drug candidates in the early stages of drug discovery. Current computational methods for compound prioritization usually focus on ranking the compounds based on one property, typically activity, with respect to a single target. However, compound selectivity is also a key property which should be deliberated simultaneously so as to minimize the likelihood of undesired side effects of future drugs. In this paper, we present a novel machine-learning based differential compound prioritization method dCPPP. This dCPPP method learns compound prioritization models that rank active compounds well, and meanwhile, preferably rank selective compounds higher via a bi-directional selectivity push strategy. The bi-directional push is enhanced by push powers that are determined by ranking difference of selective compounds over multiple bioassays. Our experiments demonstrate that the new method dCPPP achieves significant improvement on prioritizing selective compounds over baseline models.