Integrating Drug Substructures and Longitudinal Electronic Health Records for Personalized Drug Recommendation

Wenjie Du, Xuqiang Li, Jinke Feng, Shuai Zhang, Wen Zhang, Yang Wang

Keywords: Drug-Drug interaction; Drug Recommendation; Drug Substructures

TL;DR: By jointly modeling patient conditions and substructure-aware representations, Our model enhances both accuracy and interpretability, ultimately enabling safer, more personalized drug recommendations.

Abstract:

Drug recommendation systems aim to identify optimal drug combinations for patient care, balancing therapeutic efficacy and safety. Advances in large-scale longitudinal EHRs have enabled learning-based approaches that leverage patient histories such as diagnoses, procedures, and previously prescribed drugs, to model complex patient-drug relationships. Yet, many existing solutions overlook standard clinical practices that favor certain drugs for specific conditions and fail to fully integrate the influence of molecular substructures on drug efficacy and safety. In response, we propose \textbf{SubRec}, a unified framework that integrates representation learning across both patient and drug spaces. Specifically, SubRec introduces a conditional information bottleneck to extract core drug substructures most relevant to patient conditions, thereby enhancing interpretability and clinical alignment. Meanwhile, an adaptive vector quantization mechanism is designed to generate patient–drug interaction patterns into a condition-aware codebook which reuses clinically meaningful patterns, reduces training overhead, and provides a controllable latent space for recommendation. Crucially, the synergy between condition-specific substructure learning and discrete patient prototypes allows SubRec to make accurate and personalized drug recommendations. Experimental results on the real-world MIMIC III and IV demonstrate our model's advantages.
The source code is available at \href{https://anonymous.4open.science/r/DrugRecommendation-5173}{https://anonymous.4open.science/}.

Primary Area: Machine learning for sciences (e.g. climate, health, life sciences, physics, social sciences)

Submission Number: 6305