Hierarchical Multi-Relational Graph Representation Learning for Large-Scale Prediction of Drug-Drug Interactions

Most existing methods for predicting drug-drug interactions (DDI) predominantly concentrate on capturing the explicit relationships among drugs, overlooking the valuable implicit correlations present between drug pairs (DPs), which leads to weak predictions. To address this issue, this paper introduces a hierarchical multi-relational graph representation learning (HMGRL) approach. Within the framework of HMGRL, we leverage a wealth of drug-related heterogeneous data sources to construct heterogeneous graphs, where nodes represent drugs and edges denote clear and various associations. The relational graph convolutional network (RGCN) is employed to capture diverse explicit relationships between drugs from these heterogeneous graphs. Additionally, a multi-view differentiable spectral clustering (MVDSC) module is developed to capture multiple valuable implicit correlations between DPs. Within the MVDSC, we utilize multiple DP features to construct graphs, where nodes represent DPs and edges denote different implicit correlations. Subsequently, multiple DP representations are generated through graph cutting, each emphasizing distinct implicit correlations. The graph-cutting strategy enables our HMGRL to identify strongly connected communities of graphs, thereby reducing the fusion of irrelevant features. By combining every representation view of a DP, we create high-level DP representations for predicting DDIs. Two genuine datasets spanning three distinct tasks are adopted to gauge the efficacy of our HMGRL. Experimental outcomes unequivocally indicate that HMGRL surpasses several leading-edge methods in performance.