HIDEEP: a systems approach to predict hormone impacts on drug efficacy based on effect paths.

Experimental evidence has shown that some of the human endogenous hormones significantly affect drug efficacy. Since hormone status varies with individual physiological states, it is essential to understand the interplay of hormones and drugs for precision medicine. Here, we developed an in silico method to predict interactions between 283 human endogenous hormones and 590 drugs for 20 diseases including cancers and non-cancer diseases. We extracted hormone effect paths and drug effect paths from a large-scale molecular network that contains protein interactions, transcriptional regulations, and signaling interactions. If two kinds of effect paths for a hormone-drug pair intersect closely, we expect that the influence of the hormone on the drug efficacy is significant. It has been shown that the proposed method correctly distinguishes hormone-drug pairs with known interactions from random pairs in blind experiments. In addition, the method can suggest underlying interaction mechanisms at the molecular level so that it helps us to better understand the interplay of hormones and drugs.