Drug-Target Interactions Prediction Based on Signed Heterogeneous Graph Neural Networks

Abstract

Drug-target interactions (DTIs) prediction plays an important role in the process of drug discovery. Most computational methods treat it as a binary prediction problem, determining whether there are connections between drugs and targets while ignoring relational types information. Considering the positive or negative effects of DTIs will facilitate the study on comprehensive mechanisms of multiple drugs on a common target, in this work, we model DTIs on signed heterogeneous networks, through categorizing interaction patterns of DTIs and additionally extracting interactions within drug pairs and target protein pairs. We propose signed heterogeneous graph neural networks (SHGNNs), further put forward an end-to-end framework for signed DTIs prediction, called SHGNN-DTI, which not only adapts to signed bipartite networks, but also could naturally incorporate auxiliary information from drug-drug interactions (DDIs) and protein-protein interactions (PPIs). For the framework, we solve the message passing and aggregation problem on signed DTI networks, and consider different training modes on the whole networks consisting of DTIs, DDIs and PPIs. Experiments are conducted on two datasets extracted from DrugBank and related databases, under different settings of initial inputs, embedding dimensions and training modes. The prediction results show excellent performance in terms of metric indicators, and the feasibility is further verified by the case study with two drugs on breast cancer.