CBKG-DTI: Multi-Level Knowledge Distillation and Biomedical Knowledge Graph for Drug-Target Interaction Prediction

The prediction of drug-target interactions (DTIs) has emerged as a vital step in drug discovery. Recently, biomedical knowledge graph enables the utilization of multi-omics resources for modelling complex biological systems and further improves overall performance of specific predictive task. However, due to the scale and generalization of biomedical knowledge graph, it is necessary to capture task-specific knowledge from biomedical knowledge graph for DTI prediction. Moreover, although biomedical knowledge graph has rich interactions between biological entities, there still needs to contain unignorable structural information of drugs or targets in the multi-modal fusion manner. To this end, we develop a novel DTI identification framework, CBKG-DTI, which aims to distill task-specific knowledge from the complex knowledge graph to the lightweight DTI prediction model. Specifically, CBKG-DTI first introduces a hierarchy-aware knowledge graph embedding as teacher model to capture semantic hierarchy information of biomedical knowledge graph. Then, to further improve model performance, CBKG-DTI integrates information from multiple aspects such as relational information and structural information by constructing a heterogeneous network and then employs a heterogeneous graph attention network framework as the lightweight student model. Moreover, we design a multi-level distillation mechanism to improve the representation and prediction ability of the lightweight student model via capturing the representation and logit distribution of the teacher model. Finally, we conduct the extensive comparison experiments and can reach the AUC of 0.9751 and the AUPR of 0.6310 under 5-fold cross validation. This not only demonstrates the superiority of CBKG-DTI in DTI prediction, but also, more importantly, validate the effectiveness of the framework capturing task-specific knowledge from biomedical knowledge graph.