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MedGenesis: Toward a World Model for Autonomous Clinical and Translational Research

Xiao, H.; Jiang, N.; Zhang, T.; Yin, Z.; Gui, T.; Zhang, Z.; Shao, K.; Ge, J.; Wei, R.; Pan, J.; Ma, J.; Yang, L.; Zhao, Z.; Zhou, J.; Fan, J.; Jiang, Y.; Torr, P.; Zheng, S.; Wu, Y. C.; Gao, Q.

2026-06-24 health informatics
10.64898/2026.06.14.26355612 medRxiv
Show abstract

Clinical research advances slowly because its core tasks, from evidence synthesis to mechanistic validation, remain fragmented. We present MedGenesis, a clinical artificial intelligence (AI) scientist built on a world-model reasoning loop that jointly updates a Latent Hypothesis Space and a Latent Action Space under expected information gain (EIG), uncertainty reduction (UR), and a safety prior P(safe), and integrates longitudinal electronic health records (EHRs) via the Virtual Clinical Trajectory and Observation Representation (ViCTOR) for cohort retrieval, trajectory stratification, and time-to-event analysis. On two benchmarks - ClinicalResBench (1,697 expert-curated questions) and ClinicalRepBench (40 paper-reproduction tasks) - MedGenesis outperformed frontier language models and biomedical AI systems while reducing hallucination. Across 1 million patient observations spanning five clinical evidence formats, it generated traceable outputs across meta-analysis, randomized controlled trials, real-world trajectories, case-control studies, and case reports, with one wet-lab-coupled run nominating a 3-hydroxybutyrate - neutrophil axis modulating antitumor immunity. These results compress hypothesis-to-evidence cycles from years to hours, creating a continuous clinical discovery process.

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