Predicting Drug-Target Interaction Via Self-Supervised Learning

Abstract

Recent advances in graph representation learning provide new opportunities for computational drug-target interaction (DTI) prediction. However, it still suffers from deficiencies of dependence on manual labels and vulnerability to attacks. Inspired by the success of self-supervised learning (SSL) algorithms, which can leverage input data itself as supervision,we propose SupDTI, a SSL-enhanced drug-target interaction prediction framework based on a heterogeneous network (i.e., drug-protein, drug-drug, and protein-protein interaction network; drug-disease, drug-side-effect, and protein-disease association network; drug-structure and protein-sequence similarity network). Specifically, SupDTI is an end-to-end learning framework consisting of five components. First, localized and globalized graph convolutions are designed to capture the nodes' information from both local and global perspectives, respectively. Then, we develop a variational autoencoder to constrain the nodes' representation to have desired statistical characteristics. Finally, a unified self-supervised learning strategy is leveraged to enhance the nodes' representation, namely, a contrastive learning module is employed to enable the nodes' representation to fit the graph-level representation, followed by a generative learning module which further maximizes the node-level agreement across the global and local views by learning the probabilistic connectivity distribution of the original heterogeneous network. Experimental results show that our model can achieve better prediction performance than state-of-the-art methods.