Dual-Channel Learning Framework for Drug-Drug Interaction Prediction via Relation-Aware Heterogeneous Graph Transformer

Abstract

Identifying novel drug-drug interactions (DDIs) is a crucial task in pharmacology, as the interference between pharmacological substances can pose serious medical risks. In recent years, several network-based techniques have emerged for predicting DDIs. However, they primarily focus on local structures within DDI-related networks, often overlooking the significance of indirect connections between pairwise drug nodes from a global perspective. Additionally, effectively handling heterogeneous information present in both biomedical knowledge graphs and drug molecular graphs remains a challenge for improved performance of DDI prediction. To address these limitations, we propose a Transformer-based relatIon-aware Graph rEpresentation leaRning framework (TIGER) for DDI prediction. TIGER leverages the Transformer architecture to effectively exploit the structure of heterogeneous graph, which allows it direct learning of long dependencies and high-order structures. Furthermore, TIGER incorporates a relation-aware self-attention mechanism, capturing a diverse range of semantic relations that exist between pairs of nodes in heterogeneous graph. In addition to these advancements, TIGER enhances predictive accuracy by modeling DDI prediction task using a dual-channel network, where drug molecular graph and biomedical knowledge graph are fed into two respective channels. By incorporating embeddings obtained at graph and node levels, TIGER can benefit from structural properties of drugs as well as rich contextual information provided by biomedical knowledge graph. Extensive experiments conducted on three real-world datasets demonstrate the effectiveness of TIGER in DDI prediction. Furthermore, case studies highlight its ability to provide a deeper understanding of underlying mechanisms of DDIs.