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Abstract

BackgroundDisease-centered knowledge graphs (KGs) support drug repurposing and precision medicine research, yet many remain static after release while primary databases and literature continue to expand. PrimeKG (Precision Medicine Knowledge Graph) is a widely used multimodal KG providing a holistic view of diseases. However, its public release reflects a June 2021 data cutoff, omitting several years of subsequent data growth. This lag is especially consequential for rare diseases, where mechanistic and therapeutic evidence often remains scattered across publications rather than structured resources. FindingWe present PrimeKG-Plus, a refreshed, rare-disease-enriched release of PrimeKG, rebuilt from all twenty original data resources updated to their December 2025 releases and three additional resources: OpenTargets, RepurposeDrugs, and nSIDES. Beyond synchronizing biomedical databases, PrimeKG-Plus captures approximately five years of previously unavailable rare-disease knowledge from the biomedical literature, curated from 637 PubMed abstracts and PubMed Central full-text articles using a language-model-assisted workflow focused on four rare neurological disorders: Canavan disease, Niemann-Pick disease type C, Tay-Sachs disease, and Batten disease. Extracted relations were refined through entity normalization, UMLS synonym mapping, embedding-based similarity ranking, and human expert review. Network topology analysis showed improved indirect drug-disease connectivity across three to six hops and added 447,288 drug-protein-disease paths linking previously unreachable drug-disease pairs. Temporal validation using drug approval records identified 55 molecular entities approved after the original PrimeKG June 2021 cutoff, 46 of which were absent from the original graph. ConclusionPrimeKG-Plus restores the temporal relevance of PrimeKG, providing an updated resource for drug repurposing, rare-disease research, and downstream machine-learning applications.

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