Differential Compound Prioritization via Bi-Directional Selectivity Push with Power

Abstract

Effective in silico compound prioritization is critical to identify promising candidates in the early stages of drug discovery. Current methods typically focus on compound ranking based on one single property, for example, activity, against a single target. However, compound selectivity is also a key property that should be deliberated simultaneously so as to reduce 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 push strategy. The bidirectional push is enhanced with push powers that are determined by ranking difference of selective compounds over multiple bioassays. Our experiments demonstrate that the dCPPP achieves an overall 19.221% improvement on prioritizing selective compounds over baseline models.