An effective framework for predicting drug–drug interactions based on molecular substructures and knowledge graph neural network

Drug–drug interactions (DDIs) play a central role in drug research, as the simultaneous administration of multiple drugs can have harmful or beneficial effects. Harmful interactions lead to adverse reactions, some of which can be life-threatening, while beneficial interactions can promote efficacy. Therefore, it is crucial for physicians, patients, and the research community to identify potential DDIs. Although many AI-based techniques have been proposed for predicting DDIs, most existing computational models primarily focus on integrating multiple data sources or combining popular embedding methods. Researchers often overlook the valuable information within the molecular structure of drugs or only consider the structural information of drugs, neglecting the relationship or topological information between drugs and other biological objects. In this study, we propose MSKG-DDI – a two-component framework that incorporates the Drug Chemical Structure Graph-based component and the Drug Knowledge Graph-based component to capture multimodal characteristics of drugs. Subsequently, a multimodal fusion neural layer is utilized to explore the complementarity between multimodal representations of drugs. Extensive experiments were conducted using two real-world datasets, and the results demonstrate that MSKG-DDI outperforms other state-of-the-art models in binary-class, multi-class, and multi-label prediction tasks under both transductive and inductive settings. Furthermore, the ablation analysis further confirms the practical usefulness of MSKG-DDI.