A fused deep learning approach to transform drug repositioning.

Drug repositioning holds promise for discovering new therapeutic applications for existing drugs, accelerating drug development and reducing associated costs. However, current methodologies encounter difficulties in managing diverse network representations, tackling cold start issues, and handling intrinsic attribute representations. Here we introduce a Unified Knowledge-Enhanced deep learning framework for Drug Repositioning (UKEDR), which integrates knowledge graph embedding, pre-training strategies, and recommendation systems to address these challenges. To overcome the cold start issue, UKEDR utilizes a semantic similarity-driven embedding approach. Our evaluations show that UKEDR performs better than various baselines, including classical machine learning, network-based, and deep learning approaches. In cold start scenarios, it demonstrates an improved capability in handling unseen nodes and generalizing to new compounds. The model also demonstrates strong robustness on imbalanced datasets and shows excellent generalization capabilities in specific drug-centric and disease-centric cold-start scenarios, validating its potential for real-world applications.