PO.BCS02.01 · 生物信息与计算
一个医疗系统规模的多模态全患者时序基础模型
A healthcare system scale multimodal whole patient temporal foundation model
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
医疗数据在时间和模态上是碎片化的,包括临床报告、影像和实验室检测。虽然电子健康记录(EHR)捕捉了丰富的纵向健康轨迹,但当前的预测建模方法通常孤立地对单个模态进行建模,缺失了理解癌症等复杂疾病所需的上下文。为弥合这一差距,我们旨在将患者的全部病史综合为一个统一的可计算表征。
我们从一个美国主要医疗系统中整理了一个回顾性队列,涵盖来自720万名患者、跨越33年的250亿次医疗事件。该数据集整合了28种不同的临床模态,包括结构化数据(诊断、用药、生命体征、流程表和实验室结果)、临床记录和影像数据。我们开发了一个基于transformer的多模态时序基础模型,它使用模态特定的编码器对每种模态进行标记化,并随时间将各事件融合为一个统一的患者嵌入。
我们在246项下游预测任务上评估了冻结的患者嵌入,包括87种疾病的新发、56种疾病的进展、100个治疗-结局配对的治疗响应,以及三项短期运营任务。在所有任务中,该模型达到了0.77的平均AUROC,优于年龄-性别、临床文本和任务特定的监督基线。在涵盖实体和血液系统恶性肿瘤及全身治疗的肿瘤学专项任务中,该模型在新发肿瘤方面优于年龄-性别基线9%,在肿瘤进展方面优于18%,在治疗响应方面优于16%。对患者嵌入进行无监督聚类,恢复出癌症类型、合并症和治疗模式的临床上连贯的分组,形成了一个多尺度、数据驱动的医学表型图谱。相同的嵌入能够通过相似性搜索识别具有可比轨迹的患者,支持自动化队列发现和精细化临床试验匹配。基于梯度的可解释性分析识别出与临床预期一致的疾病发生和治疗响应的多模态风险因素,在患者和群体两个层面提供透明的归因。
单一的、具有时序感知能力的多模态EHR基础模型可以学习通用的全患者表征,支持对癌症结局的准确早期预测和表型分析,同时可广泛适用于多种疾病。通过将碎片化数据整合为一个持续更新的患者表征,该方法为将肿瘤学从被动、间歇性护理转向主动、持续性风险管理奠定了基础,并为风险分层、试验优化以及临床上可解释的多模态生物标志物发现提供了可扩展的基础。
查看英文原文 English abstract
Healthcare data are fragmented across time and modalities, including clinical reports, imaging, and lab tests. While Electronic Health Records (EHRs) capture rich longitudinal health trajectories, current predictive modeling approaches typically model individual modalities in isolation, missing the context needed to understand complex diseases such as cancers. To bridge this gap, we aim to synthesize the entirety of a patient's medical history into a unified computable representation.
We curated a retrospective cohort from a major U.S. healthcare system, comprising 25 billion medical events from 7.2 million patients spanning 33 years. This dataset integrates 28 distinct clinical modalities, including structured data (diagnoses, medications, vital signs, flowsheet, and laboratory results), clinical notes, and imaging data. We developed a transformer-based multimodal temporal foundation model that tokenizes each modality with modality-specific encoders and fuses events over time into a unified patient embedding.
We evaluated frozen patient embeddings on 246 downstream prediction tasks, including new onset of 87 diseases, progression of 56 diseases, treatment response for 100 therapy-outcome pairs, and three short-term operational tasks. Across all tasks, the model achieved a mean AUROC of 0.77, outperforming age-sex, clinical text, and task-specific supervised baselines. On oncology-focused tasks spanning solid and hematologic malignancies and systemic therapies, the model outperformed the age-sex baseline by 9% for new neoplasm onset, 18% for neoplasm progression, and 16% for treatment response. Unsupervised clustering of patient embeddings recovered clinically coherent groupings of cancer types, comorbidities, and treatment patterns, forming a multiscale, data-driven atlas of medical phenotypes. The same embeddings enabled similarity search to identify patients with comparable trajectories, supporting automated cohort discovery and fine-grained clinical trial matching. Gradient-based interpretability analyses identified multimodal risk factors for disease onset and treatment response that aligned with clinical expectations, providing transparent attribution at both patient and population level.
A single multimodal, temporally aware EHR foundation model can learn general-purpose whole-patient representations that support accurate early prediction and phenotyping of cancer outcomes while remaining applicable across diverse diseases. By consolidating fragmented data into a continuously updated patient representation, this approach lays the groundwork for shifting oncology from reactive, episodic care to proactive, continuous risk management, and provides a scalable basis for risk stratification, trial optimization, and discovery of clinically interpretable multimodal biomarkers.
利益披露 Disclosure
A. Zhang, None..
T. Ding, None..
S. J. Wagner, None..
C. Tian, None..
M. Lu, None..
A. Misrahi, None..
J. E. Lewis, None..
R. Pettit, None..
L. P. Le, None..
F. Mahmood, None.