RAG-GNN: Integrating Retrieved Knowledge with Graph Neural Networks for Precision Medicine

Abstract: Network topology excels at structural predictions but fails to capture functional semantics encoded in biomedical literature. We present a retrieval-augmented generation (RAG) embedding framework that integrates graph neural network representations with dynamically retrieved literature-derived knowledge through contrastive learning. Benchmarking against ten embedding methods reveals task-specific complementarity: topology-focused methods achieve near-perfect link prediction (GCN: 0.983 AUROC), while RAG-GNN is the only method achieving positive silhouette scores for functional clustering (0.001 vs. negative scores for all baselines). Information-theoretic decomposition shows network topology contributes 77.3% of predictive information, while retrieved documents provide 8.6% unique information. Applied to cancer signaling networks (379 proteins, 3,498 interactions), the framework identifies DDR1 as a therapeutic target based on retrieved evidence of synthetic lethality with KRAS mutations. These results establish that topology-only and retrieval-augmented approaches serve complementary purposes: structural prediction tasks are solved by network topology alone, while functional interpretation uniquely benefits from retrieved knowledge.