Organ-Agents: Virtual Human Physiology Simulator via LLMs

• URL: http://arxiv.org/abs/2508.14357v1
• Date: Wed, 20 Aug 2025 01:58:45 GMT
• Title: Organ-Agents: Virtual Human Physiology Simulator via LLMs
• Authors: Rihao Chang, He Jiao, Weizhi Nie, Honglin Guo, Keliang Xie, Zhenhua Wu, Lina Zhao, Yunpeng Bai, Yongtao Ma, Lanjun Wang, Yuting Su, Xi Gao, Weijie Wang, Nicu Sebe, Bruno Lepri, Bingwei Sun,
• Abstract summary: Organ-Agents is a multi-agent framework that simulates human physiology via LLM-driven agents.<n>We curated data from 7,134 sepsis patients and 7,895 controls, generating high-resolution trajectories across 9 systems and 125 variables.<n>Organ-Agents achieved high simulation accuracy on 4,509 held-out patients, with per-system MSEs 0.16 and robustness across SOFA-based severity strata.
• Score: 66.40796430669158
• License: http://creativecommons.org/publicdomain/zero/1.0/
• Abstract: Recent advances in large language models (LLMs) have enabled new possibilities in simulating complex physiological systems. We introduce Organ-Agents, a multi-agent framework that simulates human physiology via LLM-driven agents. Each Simulator models a specific system (e.g., cardiovascular, renal, immune). Training consists of supervised fine-tuning on system-specific time-series data, followed by reinforcement-guided coordination using dynamic reference selection and error correction. We curated data from 7,134 sepsis patients and 7,895 controls, generating high-resolution trajectories across 9 systems and 125 variables. Organ-Agents achieved high simulation accuracy on 4,509 held-out patients, with per-system MSEs <0.16 and robustness across SOFA-based severity strata. External validation on 22,689 ICU patients from two hospitals showed moderate degradation under distribution shifts with stable simulation. Organ-Agents faithfully reproduces critical multi-system events (e.g., hypotension, hyperlactatemia, hypoxemia) with coherent timing and phase progression. Evaluation by 15 critical care physicians confirmed realism and physiological plausibility (mean Likert ratings 3.9 and 3.7). Organ-Agents also enables counterfactual simulations under alternative sepsis treatment strategies, generating trajectories and APACHE II scores aligned with matched real-world patients. In downstream early warning tasks, classifiers trained on synthetic data showed minimal AUROC drops (<0.04), indicating preserved decision-relevant patterns. These results position Organ-Agents as a credible, interpretable, and generalizable digital twin for precision diagnosis, treatment simulation, and hypothesis testing in critical care.

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