Cardio21

PYRIN-PLAQUE Digital Twin investigates whether MEFV/pyrin inflammasome biology can be separated from the saturated NLRP3 atherosclerosis story and mapped to human plaque cell states using only public data. We built an auditable Claude Science workflow that combines a 57-claim literature evidence graph, verified public datasets, single-cell plaque module scoring, bulk plaque triangulation, a dimensionless pyroptosis ODE, caveat-aware priority scoring, and reviewer-agent audits. The project deliberately separates a pyrin-specific regulatory backbone from NLRP3 and excludes shared downstream genes such as PYCARD, CASP1, GSDMD, IL1B, and IL18 from discriminative scoring. In GSE159677 single-cell plaque data, MEFV was sparse overall but enriched in macrophage/myeloid cells, and PYRIN_BACKBONE scored highest in the myeloid compartment while NLRP3 localized differently. In GSE120521 bulk plaque data, PYRIN_BACKBONE rose in unstable plaque, but this signal largely collapsed after myeloid-marker adjustment. The ODE model similarly suggested that generic inflammatory priming may dominate pyrin-specific threshold effects. The result is not a validated drug target or clinical claim. It is a transparent, reproducible, caveat-aware hypothesis engine that prioritizes the MEFV/pyrin threshold axis for future experimental validation while preserving confounded and weak findings instead of hiding them.

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