Drug-Target Interaction Prediction with PIGLET

Abstract

Drug-target interaction (DTI) prediction is a key task for computed-aided drug development that has been widely approached by deep learning models. Despite extremely high reported performance, these models have yet to find widespread success in accelerating real-world drug discovery. In contrast with the most common approach of creating embeddings from one-dimensional or three-dimensional representations of the input drug and input target, we create a novel graph transformer method for DTI prediction that operates on a proteome-wide knowledge graph of binding pocket similarity, protein-protein interactions, drug similarity, and known binding relationships. We benchmark our method, named PIGLET, against existing DTI prediction models on the Human dataset. We assess performance with two different splitting strategies: the frequently-reported random split, and a novel, more rigorous drug-based split. All models perform similarly well on the random split, and PIGLET outperforms all models on the drug-based split. We highlight the utility of PIGLET through a real-world drug discovery case study.