用大模型+推理机制,从少量人群统计数据中发现疾病演化规律。
LLM-Guided ODE Discovery and Parameter Inference from Small-Cohort Aggregate Data

- 大模型提出微分方程结构候选,智能体迭代优化参数分布。
- 在仅231个观察值的罕见病数据上,准确恢复出功能一致的方程结构。
- 适合数据稀缺、隐私敏感的临床研究,如罕见病机制探索。
基于常微分方程(ODE)的机制建模可提供复杂动态过程的可解释描述,并实现潜在机制推断,在临床场景中尤为关键。然而,在罕见病中,模型结构与参数通常未知,且个体数据稀少、噪声大、异质性强,还受隐私限制。此时,群体层面的汇总统计量是一种实用的隐私保护数据形式,而捕捉异质性需将参数建模为分布而非固定值。但现有方法无法仅从汇总统计量中联合发现ODE结构并优化参数分布。本文提出AgentODE,一个端到端框架:大模型(LLM)生成候选ODE结构,工具增强的推理智能体通过诊断-更新循环迭代精炼参数分布,仅使用群体层面汇总统计量。我们在三个跨领域基准问题及两个临床数据集(包括罕见病隐性营养不良性大疱性表皮松解症,RDEB)上评估该方法,后者仅有46名患者共231个观测值。AgentODE在所有设置下均恢复出功能一致的ODE结构;在RDEB实验中,仅依赖汇总统计量的推理能促进机制合理结构发现,而拥有个体数据的基线虽预测性能更优,却推导出不合理结构。AgentODE为直接从群体汇总数据进行罕见病机制建模开辟了新可能,突破了传统数据稀缺与隐私约束的瓶颈。
原文摘要 · Abstract (English)
Mechanistic modeling via ordinary differential equations (ODEs) provides interpretable descriptions of complex dynamics and enables inference of underlying mechanisms, which is particularly valuable in clinical settings. However, in rare diseases, both the structure and parameters of the model are typically unknown, while individual-level data is scarce, noisy, heterogeneous, and subject to privacy constraints. In such settings, population-level summary statistics provide a practical privacy-preserving data representation, while capturing heterogeneity further requires modeling parameters as distributions rather than fixed values. Yet no existing method jointly discovers ODE structure and refines parameter distributions solely from summary statistics. We present AgentODE, an end-to-end framework that addresses this gap. An LLM proposes candidate ODE structures, while a tool-augmented inference agent iteratively refines parameter distributions through a diagnosis--update loop, operating on population-level summary statistics alone. We evaluate AgentODE on three benchmark problems across different fields and two clinical datasets, including the rare disease recessive dystrophic epidermolysis bullosa (RDEB), with only 231 observations across 46 patients. AgentODE recovers functionally consistent ODE structures across all settings, and experiments on RDEB demonstrates that in sparse and noisy data settings reasoning from summary statistics promotes mechanistically principled structure discovery, whereas baselines with individual-level data access recover implausible structures despite better predictive performance. AgentODE opens new possibilities for mechanistic modeling of rare diseases directly from population-level summary statistics, where data scarcity and privacy constraints have traditionally limited such analyses.
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