Heterogeneous sampled subgraph neural networks with knowledge distillation to enhance double-blind compound-protein interaction prediction

Abstract

Identifying binding compounds against a target protein is crucial for large-scale virtual screening in drug development. Recently, network-based methods have been developed for compound-protein interaction (CPI) prediction. However, they are difficult to be applied to unseen (i.e., never-seen-before) proteins and compounds. In this study, we propose SgCPI to incorporate local known interacting networks to predict CPI interactions. SgCPI randomly samples the local CPI network of the query compound-protein pair as a subgraph and applies a heterogeneous graph neural network (HGNN) to embed the active/inactive message of the subgraph. For unseen compounds and proteins, SgCPI-KD takes SgCPI as the teacher model to distillate its knowledge by estimating the potential neighbors. Experimental results indicate: (1) the sampled subgraphs of the CPI network introduce efficient knowledge for unseen molecular prediction with the HGNNs, and (2) the knowledge distillation strategy is beneficial to the double-blind interaction prediction by estimating molecular neighbors and distilling knowledge.