DTI-Voodoo: machine learning over interaction networks and ontology-based background knowledge predicts drug–target interactions

MOTIVATION: In silico drug–target interaction (DTI) prediction is important for drug discovery and drug repurposing. Approaches to predict DTIs can proceed indirectly, top-down, using phenotypic effects of drugs to identify potential drug targets, or they can be direct, bottom-up and use molecular information to directly predict binding affinities. Both approaches can be combined with information about interaction networks. RESULTS: We developed DTI-Voodoo as a computational method that combines molecular features and ontology-encoded phenotypic effects of drugs with protein–protein interaction networks, and uses a graph convolutional neural network to predict DTIs. We demonstrate that drug effect features can exploit information in the interaction network whereas molecular features do not. DTI-Voodoo is designed to predict candidate drugs for a given protein; we use this formulation to show that common DTI datasets contain intrinsic biases with major effects on performance evaluation and comparison of DTI prediction methods. Using a modified evaluation scheme, we demonstrate that DTI-Voodoo improves significantly over state of the art DTI prediction methods. AVAILABILITY AND IMPLEMENTATION: DTI-Voodoo source code and data necessary to reproduce results are freely available at https://github.com/THinnerichs/DTI-VOODOO. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.