用Transformer从横断面数据推断疾病进展的连续与顺序事件
TEMPO: Transformers for Temporal Disease Progression from Cross-Sectional Data

- 将生物标志物和患者分别视为令牌,通过双分支Transformer建模进展序列
- 在合成数据上比现有方法降低52.89%的事件排序误差、25.33%的分期误差
- 适用于阿尔茨海默病等复杂疾病进展研究,无需定制推断算法
事件型模型(EBM)可从横断面数据推断生物标志物进展,但通常仅限于有序序列,且依赖严格模型假设。我们提出 extsc{Tempo},一种基于模拟监督学习的Transformer架构,能够同时学习事件的有序与连续序列。 extsc{Tempo} 包含两个Transformer模块:一个将生物标志物视为令牌以推断事件顺序;另一个将患者视为令牌,以其各生物标志物异常状态表示,以推断疾病阶段。在合成基准测试中, extsc{Tempo} 相较于最先进方法SA-EBM,事件序列的归一化Kendall's Tau距离降低52.89%,阶段预测的均方误差降低25.33%,高维场景下降幅更大(58.88%和61.10%)。应用于ADNI数据集时, extsc{Tempo} 恢复出符合生物学常识的阿尔茨海默病进展路径:早期海马颞叶萎缩,继之淀粉样蛋白沉积与认知下降,晚期出现tau病理及全局神经退行性加速——与已有疾病模型基本一致。 extsc{Tempo} 还免去了定制推断算法的需求,支持快速验证生成性假说。
原文摘要 · Abstract (English)
Event-Based Models (EBMs) infer biomarker progression from cross-sectional data but typically only as ordinal sequences and rely on rigid model assumptions. We propose \textsc{Tempo}, a Transformer architecture that learns both ordinal and continuous event sequences through simulation-based supervised learning. \textsc{Tempo} uses two Transformer modules: one treats biomarkers as tokens to infer event sequencing; the other treats patients as tokens, representing each by their per-biomarker abnormality profile, to infer patients' disease stages. On synthetic benchmarks, \textsc{Tempo} reduces normalized Kendall's Tau distance by 52.89\% and staging MAE by 25.33\% compared to state-of-the-art SA-EBM, with larger reductions in high-dimensional settings (58.88\% and 61.10\%). Applied to ADNI, \textsc{Tempo} recovers a biologically plausible Alzheimer's progression: early medial temporal atrophy, followed by amyloid accumulation and cognitive decline, and late-stage tau pathology with terminal acceleration of global neurodegeneration -- broadly consistent with established disease models. \textsc{Tempo} also eliminates the need to derive custom inference algorithms and enables rapid empirical comparison of generative hypotheses.
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