ML-DTI: Mutual Learning Mechanism for Interpretable Drug–Target Interaction Prediction

Deep learning (DL) provides opportunities for the identification of drug–target interactions (DTIs). The challenges of applying DL lie primarily with the lack of interpretability. Also, most of the existing DL-based methods formulate the drug and target encoder as two independent modules without considering the relationship between them. In this study, we propose a mutual learning mechanism to bridge the gap between the two encoders. We formulated the DTI problem from a global perspective by inserting mutual learning layers between the two encoders. The mutual learning layer was achieved by multihead attention and position-aware attention. The neural attention mechanism also provides effective visualization, which makes it easier to analyze a model. We evaluated our approach using three benchmark kinase data sets under different experimental settings and compared the proposed method to three baseline models. We found that the four methods yielded similar results in the random split setting (training and test sets share common drugs and targets), while the proposed method increases the predictive performance significantly in the orphan-target and orphan-drug split setting (training and test sets share only targets or drugs). The experimental results demonstrated that the proposed method improved the generalization and interpretation capability of DTI modeling.