GA-ENs: A novel drug–target interactions prediction method by incorporating prior Knowledge Graph into dual Wasserstein Generative Adversarial Network with gradient penalty

Abstract

Bipartite graph-based drug–target interactions (DTIs) prediction methods are commonly limited by the sparse structure of the graph, resulting in acquiring suboptimal node feature representations. In addition, these defective node features will also interfere with the representation quality of corresponding edge features. To alleviate the sparsity of bipartite graph and get better node representation, according to the prior Knowledge Graph (KG), we developed a novel prediction model based on Variational Graph Auto-Encoder (VGAE) combined with our proposed dual Wasserstein Generative Adversarial Network with gradient penalty strategy (dual-WGAN-GP) for generating edge information and augmenting their representations. Specifically, GA-ENs first utilized dual-WGAN-GP to fill possible edges by a prior KG containing various molecular associations knowledge when constructing a bipartite graph of known DTIs. Moreover, we utilized the KG transfer probability matrix to redefine the drug–drug and target–target similarity matrix, thus constructing the final graph adjacent matrix. Combining graph adjacent matrix with node features, we learn node representations by VGAE and augment them by utilizing dual-WGAN-GP again, thus obtaining final edge representations. Finally, a fully connected network with three layers was designed to predict potential DTIs. Extensive experiment results show that GA-ENs has excellent performance for DTIs prediction and could be a supplement tool for practical DTIs biological screening.