arXiv:2604.27899cs.AI2026-04被引 1

用生成模型模拟人体生理变化,可预测疾病风险并虚拟测试干预效果。

Simulating clinical interventions with a generative multimodal model of human physiology

  • 基于667项生理指标构建生成式模型,学习个体健康轨迹演变规律。
  • 在4个独立队列中预测27种疾病与死亡风险,优于传统临床评分模型。
  • 能虚拟模拟个性化营养干预,预测结果与真实试验高度一致。

理解人体健康随时间的变化及个体对干预反应的差异,仍是医学核心挑战。本文提出HealthFormer,一个仅含解码器的Transformer模型,基于超过15,000名深度表型个体的多访视数据进行训练。将每位参与者在血清生物标志物、体成分、睡眠生理、连续血糖监测、肠道微生物组、可穿戴设备获取生理数据及行为用药暴露等七个领域的667项测量值转化为序列令牌,训练模型生成性地预测个体跨域生理轨迹。通过单一生成目标,可表达多种临床相关任务作为模型查询。无需特定任务微调,HealthFormer在四个独立队列中对30个新发疾病与死亡终点的预测表现提升27项,且每项均优于现有临床风险评分。进一步验证其可模拟虚拟干预:在保留的个性化营养试验中,条件化预测恢复了个体六个月内的生物标志物变化(如舒张压相关性Pearson r=0.78)。在41个来自已发表试验的随机干预-结局对比中,预测效应方向完全一致,预测均值在30例内落入实际报告的95%置信区间。HealthFormer被视为初步的健康世界模型,其上可衍生出预测、风险分层与干预模拟等任务,为临床数字孪生奠定基础。

原文摘要 · Abstract (English)

Understanding how human health changes over time, and why responses to interventions vary between individuals, remains a central challenge in medicine. Here we present HealthFormer, a decoder-only transformer that models the human physiological trajectory generatively, by training on data from the Human Phenotype Project, a multi-visit cohort of over 15,000 deeply phenotyped individuals. We tokenise each participant's health trajectory across 667 measurements spanning seven domains: blood biomarkers, body composition, sleep physiology, continuous glucose monitoring, gut microbiome, wearable-derived physiology, and behaviour and medication exposure. We train HealthFormer to forecast individual physiological trajectories across these domains, and from this single generative objective a range of clinically relevant tasks can be expressed as queries on the model. We show that, without task-specific training, HealthFormer transfers to four independent cohorts and improves prediction for 27 of 30 incident-disease and mortality endpoints, exceeding established clinical risk scores in every comparison. We further show that the model can simulate interventions in silico: in a held-out personalised-nutrition trial, intervention-conditioned predictions recover individual six-month biomarker changes (e.g., Pearson r = 0.78 for diastolic blood pressure). Across 41 randomised intervention-outcome comparisons drawn from published trials, our results show that the predicted direction of effect agrees in every case, and the predicted mean falls within the reported 95% confidence interval in 30 cases. We position HealthFormer as an initial health world model, from which forecasting, risk stratification, and intervention-conditioned simulation arise as queries, providing a basis for clinical digital twins.

生成模型生理预测数字孪生干预模拟

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