Semi-supervised heterogeneous graph contrastive learning for drug-target interaction prediction

Abstract

Identification of drug-target interactions (DTIs) is an important step in drug discovery and drug repositioning. In recent years, graph-based methods have attracted great attention and show advantages on predicting potential DTIs. However, these methods face the problem that the known DTIs are very limited and expensive to obtain, which decreases the generalization ability of the methods. Self-supervised contrastive learning is independent of labeled DTIs, which can mitigate the impact of the problem. Therefore, we propose a framework SHGCL-DTI for predicting DTIs, which supplements the classical semi-supervised DTI prediction task with an auxiliary graph contrastive learning module. Specifically, we generate representations for the nodes through the neighbor view and meta-path view, and define positive and negative pairs to maximize the similarity between positive pairs from different views. Subsequently, SHGCL-DTI reconstructs the original heterogeneous network to predict the potential DTIs. The experiments on the public dataset show that SHGCL-DTI has significant improvement in different scenarios, compared with existing state-of-the-art methods. We also demonstrate that the contrastive learning module improves the prediction performance and generalization ability of SHGCL-DTI through ablation study. In addition, we have found several novel predicted DTIs supported by the biological literature. The data and source code are available at: https://github.com/TOJSSE-iData/SHGCL-DTI.

Keywords: Deep learning; Drug–target interaction prediction; Graph contrastive learning; Graph neural network; Heterogeneous network.