A knowledge graph-based method for drug-drug interaction prediction with contrastive learning.

Abstract

Precisely predicting Drug-Drug Interactions (DDIs) carries the potential to elevate the quality and safety of drug therapies, protecting the well-being of patients, and providing essential guidance and decision support at every stage of the drug development process. In recent years, leveraging large-scale biomedical knowledge graphs has improved DDI prediction performance. However, the feature extraction procedures in these methods are still rough. More refined features may further improve the quality of predictions. To overcome these limitations, we develop a knowledge graph-based method for multi-typed DDI prediction with contrastive learning (KG-CLDDI). In KG-CLDDI, we combine drug knowledge aggregation features from the knowledge graph with drug topological aggregation features from the DDI graph. Additionally, we build a contrastive learning module that uses horizontal reversal and dropout operations to produce high-quality embeddings for drug-drug pairs. The comparison results indicate that KG-CLDDI is superior to state-of-the-art models in both the transductive and inductive settings. Notably, for the inductive setting, KG-CLDDI outperforms the previous best method by 17.49% and 24.97% in terms of AUC and AUPR, respectively. Furthermore, we conduct the ablation analysis and case study to show the effectiveness of KG-CLDDI. These findings illustrate the potential significance of KG-CLDDI in advancing DDI research and its clinical applications. The codes of KG-CLDDI are available at https://github.com/jianzhong123/KG-CLDDI.