Ontology-Based Post-Coordinated Expression Assembly: from Clinical Narrative to Queryable Knowledge Graphs

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.

Clinical records contain rich evidence about patient state, but converting that evidence into reliable, structured knowledge graphs remains difficult because extraction errors, ontology mismatch, missing relations, and temporal ambiguity can propagate into downstream systems. We propose a clinical knowledge graph construction and refinement framework that combines multi-agent relation proposal, ontology-aware normalization, deterministic evidence scoring, and JEPA-based latent refinement. Rather than treating a clinical knowledge graph as a static extraction artifact, we treat it as a predictive patient-state representation. For each admission, the system constructs an evidence-scored graph from structured MIMIC-IV records and inferred clinical cross-links, then learns to recover held-out clinical relations from the observed graph context. We evaluate the refiner with leakage-free leave-one-out edge recovery (MRR and Hits@k) and held-out batch-mask evaluation (AUC and MRR). To isolate the contribution of discharge-note context, we compare a note-embedding-free configuration with a note-augmented configuration that injects real discharge-note representations only into note-grounded entities. Under the same cohort and evaluation protocol, entity-grounded note injection improves overall leave-one-out MRR by 31% relative improvement.

Clinical decision-support outputs can lack an au- ditable link between patient observations, encoded knowledge, conclusions, and recommendations. We present the CKG Clinical Explanation Engine, a downstream layer for a frozen, training-free clinical knowledge-graph reasoner that converts patient inference states and disease knowledge into typed facts, explicit rule-application traces, provenance-linked conclusions, and policy-licensed recommendations. The design separates measurement availability, representation completeness, and disease-specific activation; consequently, observed zero-activation evience is not treated as missing and partial representation is distinct from unobserved evidence. Optional language generation is restricted to symbolically licensed content. Across five usable workbooks (6,720 patients; 20,160 patient-disease traces; 1,021,440 feature-evidence rows), IG-range validity and knowledge provenance were 100%, numerical cross-sheet fidelity was 100% (120,960/120,960), and exported logical/report trace completeness was 100% (20,160/20,160). Availability representation consistency was 99.7028% (1,018,404/1,021,440); all 3,036 disagreements were confined to three systematic feature-cohort patterns. The corpus contained 86,783 observed zero-activation and 139,949 observed partially represented instances. A separate seeded 25-patient end-to-end audit completed without execution failure and passed all pre-specified trace, licensing, provenance, and state-consistency checks. These results establish structural and implementation auditability, not clinical correctness or utility.