ChronoMedKG: A Temporally-Grounded Biomedical Knowledge Graph and Benchmark for Clinical Reasoning

Biomedical knowledge graphs (KGs) treat disease associations as static facts, but temporal information is crucial for clinical reasoning, e.g., a symptom diagnostic of one disease at age 3 may imply a different disease at age 13. Existing KGs such as PrimeKG, Hetionet, and iKraph do not encode when a finding becomes clinically relevant over the course of a disease. This limits their usefulness for longitudinal clinical reasoning and retrieval augmentation. We introduce ChronoMedKG, a temporal biomedical knowledge graph that contains 460,497 evidence-linked triples (filtered from 13M raw extractions) covering 13,431 diseases. Each association is tied to temporal components like onset window or progression stage, which are backed by PMID-traceable evidence and a multi-signal credibility score. The graph is constructed through a disease-autonomous multi-agent pipeline in which multiple frontier LLMs independently extract knowledge from PubMed and PMC literature. Only those relations are kept that are supported by multi-model consensus, survive credibility filtering, as well as ontology alignment. ChronoMedKG scored 92.7% agreement against Orphadata and adds temporal grounding for 6,250 diseases absent from HPOA, Orphadata, and Phenopackets, including 1,657 Orphanet-coded rare diseases. We further introduce ChronoTQA, a benchmark of 3,341 questions across eight task types (six temporal plus two static controls), with a 12-question supplementary probe. Frontier LLMs lose roughly 30 points moving from static to temporal questions; ChronoMedKG retrieval rescues 47-65% of their long-tail failures, against 17-29% for HPOA-RAG. As such, ChronoMedKG provides a crucial temporal axis for retrieval-augmented clinical systems that was previously absent.

S4CMDR: a metadata repository for electronic health records

Background: Electronic health records (EHRs) enable machine learning for diagnosis, prognosis, and clinical decision support. However, EHR standards vary by country and hospital, making records often incompatible. This limits large-scale and cross-clinical machine learning. To address such complexity, a metadata repository cataloguing available data elements, their value domains, and their compatibility is an essential tool. This allows researchers to leverage relevant data for tasks such as identifying undiagnosed rare disease patients. Results: Within the Screen4Care project, we developed S4CMDR, an open-source metadata repository built on ISO 11179-3, based on a middle-out metadata standardisation approach. It automates cataloguing to reduce errors and enable the discovery of compatible feature sets across data registries. S4CMDR supports on-premise Linux deployment and cloud hosting, with state-of-the-art user authentication and an accessible interface. Conclusions: S4CMDR is a clinical metadata repository registering and discovering compatible EHR records. Novel contributions include a microservice architecture, a middle-out standardisation approach, and a user-friendly interface for error-free data registration and visualisation of metadata compatibility. We validate S4CMDR's case studies involving rare disease patients. We invite clinical data holders to populate S4CMDR using their metadata to validate the generalisability and support further development.