DTI-HETA: prediction of drug–target interactions based on GCN and GAT on heterogeneous graph

Abstract

Abstract Drug–target interaction (DTI) prediction plays an important role in drug repositioning, drug discovery and drug design. However, due to the large size of the chemical and genomic spaces and the complex interactions between drugs and targets, experimental identification of DTIs is costly and time-consuming. In recent years, the emerging graph neural network (GNN) has been applied to DTI prediction because DTIs can be represented effectively using graphs. However, some of these methods are only based on homogeneous graphs, and some consist of two decoupled steps that cannot be trained jointly. To further explore GNN-based DTI prediction by integrating heterogeneous graph information, this study regards DTI prediction as a link prediction problem and proposes an end-to-end model based on HETerogeneous graph with Attention mechanism (DTI-HETA). In this model, a heterogeneous graph is first constructed based on the drug–drug and target–target similarity matrices and the DTI matrix. Then, the graph convolutional neural network is utilized to obtain the embedded representation of the drugs and targets. To highlight the contribution of different neighborhood nodes to the central node in aggregating the graph convolution information, a graph attention mechanism is introduced into the node embedding process. Afterward, an inner product decoder is applied to predict DTIs. To evaluate the performance of DTI-HETA, experiments are conducted on two datasets. The experimental results show that our model is superior to the state-of-the-art methods. Also, the identification of novel DTIs indicates that DTI-HETA can serve as a powerful tool for integrating heterogeneous graph information to predict DTIs.