Knowledge-Driven and Relation-Aware Synergistic Learning for Drug Repositioning.

Abstract

As an effective and low-risk approach to identify new therapeutic pathways for existing drugs, drug repositioning has been extensively utilized to expedit drug discovery processes. However, current knowledge graph (KG)-based methodologies encounter several hurdles in this context. Firstly, most graph neural network (GNN)- based approaches fail to adequately capture the intricate relationships between drug-drug, drug-disease, or diseasedisease. Secondly, the subtle synergistic mechanisms between drugs and diseases remain underexplored. Lastly, the training of knowledge graph embedding (KGE) methods is susceptible to noise, leading to unstable model optimization. To address these challenges, we intruduce KRANE, a knowledge-driven and relation-aware synergistic learning method for drug repositioning. KRANE addresses these issues through three innovative modules. Firstly, we design a relation-aware feature extractor (RAFE), which utilizes the contextual triples attention scores in KG to effectively integrate drug-related knowledge and enhance the representation of complex relational features. Secondly, we adopt a synergistic feature reconstruction module as a decoder to extract synergistic heterogeneous feature interactions between drugs and diseases from entity and relation representations. Finally, we propose a knowledgeregulated loss function to mitigate the impact of noise on model training. Experiments conducted on three publicly available datasets demonstrate that KRANE significantly outperforms existing methods. The source code and datasets are available at https://github.com/qifen37/KRANE.