ArticlemedRxiv : the preprint server for health sciences2026
A phenotype-to-mechanism framework links phenome-wide comorbidity architecture to molecular mechanisms and therapeutic discovery in complex diseases.
Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
16 authors.
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Abstract
Complex human diseases exhibit substantial clinical heterogeneity driven by poorly understood molecular mechanisms, while many also lack sufficient molecular and omics data for mechanistic investigation, hindering therapeutic development. We introduce PiMInfer, a "phenotype-to-mechanism" framework that leveraged largely available real-world clinical data-based deep phenotypic characterizations with a biomedical knowledge graph approach to resolve disease clinical heterogeneity into phenotype-informed molecular modules, thereby accelerating therapeutic target discovery. We applied PiMInfer to investigate Hidradenitis Suppurativa (HS), an autoimmune skin disease with poorly understood pathogenesis and limited treatment options. PiMInfer identified a coherent, phenotype-informed HS gene module (PiHSM) and functional endotypes, which were validated using multimodal evidence.
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