D4: Deep Drug-drug interaction Discovery and Demystification

MotivationDrug-drug interactions (DDIs) are complex processes which may depend on many clinical and non-clinical factors. Identifying and distinguishing ways in which drugs interact remains a challenge. To minimize DDIs and to personalize treatment based on accurate stratification of patients, it is crucial that mechanisms of interaction can be identified. Most DDIs are a consequence of metabolic mechanisms of interaction, but DDIs with different mechanisms occur less frequently and are therefore more difficult to identify. ResultsWe developed a method (D4) for computationally identifying potential DDIs and determining whether they interact based on one of eleven mechanisms of interaction. D4 predicts DDIs and their mechanisms through features that are generated through a deep learning approach from phenotypic and functional knowledge about drugs, their side-effects and targets. Our findings indicate that our method is able to identify known DDIs with high accuracy and that D4 can determine mechanisms of interaction. We also identify numerous novel and potential DDIs for each mechanism of interaction and evaluate our predictions using DDIs from adverse event reporting systems. Availabilityhttps://github.com/bio-ontology-research-group/D4 Contactarnoor@kau.edu.sa and robert.hoehndorf@kaust.edu.sa