DMHGNN: Double multi-view heterogeneous graph neural network framework for drug-target interaction prediction

Abstract

Accurate identification of drug-target interactions (DTIs) plays a crucial role in drug discovery. Compared with traditional experimental methods that are labor-intensive and time-consuming, computational methods for drug-target interactions prediction are more popular in recent years. Conventional computational methods almost simply view heterogeneous network constructed by the drug-related and protein-related dataset instead of comprehensively exploring drug-protein pair (DPP) information. To address this limitation, we proposed a Double Multi-view Heterogeneous Graph Neural Network framework for drug-target interaction prediction (DMHGNN). In DMHGNN, one multi-view heterogeneous graph neural network is based on meta-paths and denoising autoencoder for protein-, drug-related heterogeneous network learning, and another multi-view heterogeneous graph neural network is based on multi-channel graph convolutional network for drug-protein pair similarity network learning. First, a meta-path-based graph encoder with the attention mechanism is used for substructure learning of complex relationships from heterogeneous network constructed by proteins, drugs, side-effects and diseases, obtaining key information that is easy to be ignored in global learning of heterogeneous networks, and multi-source neighbouring features for drugs and proteins are learned from heterogeneous network via denoising auto-encoder model. Then, multi-view graphs of drug-protein pairs (DPPs) including the topology graph, semantics graph and collaborative graph with shared weights are constructed, and the multi-channel graph convolutional network (GCN) is utilized to learn the deep representation of DPPs. Finally, a multi-layer fully connection network is trained to predict drug-target interactions. Experiments have demonstrated its effectiveness and better performance than state-of-the-art methods.

Keywords: DTIs prediction; Double multi-view graphs; Drug-protein pair network; Meta-path-based graph encoder.