Learning to take it personally: Precision drug repurposing through patient-specific loss on knowledge graphs using Biobank data

OBJECTIVE: Precision medicine requires drug repurposing methods that adapt to individual patient profiles while working within regulatory frameworks. Existing approaches apply uniform models to all patients, only using individual factors as inputs or filters. METHODS: Our framework instead integrates patient-specific profiles into the learning algorithm through a customized loss function. We combine standard link prediction with UK Biobank data-integrating polygenic risk scores, biomarker expressions, and medical history. RESULTS: Evaluated on a biomedical knowledge graph connecting 61,000+ entities through 1.2+ million relations, our approach improves drug repurposing quality with AUPRC improvements ranging from 1.3× to 5.4× across patients. Case studies on Alzheimer's Disease patients reveal drug candidates with stronger AD evidence and patient-specific mechanisms. Our loss function identifies influential diseases and biomarkers for each patient, enhancing interpretability while providing biologically relevant recommendations tailored to individual profiles. CONCLUSION: This approach represents a fundamental shift from treating personalization as data preprocessing to embedding it within the learning objective itself.