arXiv:2602.10303cs.LGq-bio.QM2026-02

用微分方程神经网络建模区间删失生存数据,无需比例风险假设。

ICODEN: Ordinary Differential Equation Neural Networks for Interval-Censored Data

  • 基于ODE的神经网络建模危险函数,通过积分求累积风险。
  • 在高维基因数据下仍保持稳定预测,对线性和非线性效应均有效。
  • 适合高维生物医学数据,支持个性化风险分组识别。

当事件发生时间仅知在某个时间区间内(区间删失)时,预测事件发生时间极具挑战。现有生存分析方法常依赖强假设或难以处理高维协变量。本文提出ICODEN,一种基于常微分方程的神经网络模型,通过深度神经网络建模危险函数,并通过求解常微分方程获得累积危险函数。该方法不依赖比例风险假设,也不需预设危险函数的参数形式,从而实现灵活的生存建模。在包含比例与非比例风险、线性与非线性协变量效应的多种模拟设置中,ICODEN始终表现良好,且随着预测变量数量增加仍保持稳定。在阿尔茨海默病神经影像计划(ADNI)多个阶段及两项年龄相关性眼病研究(AREDS、AREDS2)的数据应用中,ICODEN在预测阿尔茨海默病或晚期年龄相关性黄斑变性(AMD)发病时间方面表现稳健。模型能有效利用数百至千余个单核苷酸多态性(SNPs),并支持数据驱动的亚组识别,揭示不同人群的进展风险差异。这些结果表明,ICODEN是一种适用于高维生物医学场景下区间删失生存数据预测的无假设依赖工具。

原文摘要 · Abstract (English)

Predicting time-to-event outcomes when event times are interval censored is challenging because the exact event time is unobserved. Many existing survival analysis approaches for interval-censored data rely on strong model assumptions or cannot handle high-dimensional predictors. We develop ICODEN, an ordinary differential equation-based neural network for interval-censored data that models the hazard function through deep neural networks and obtains the cumulative hazard by solving an ordinary differential equation. ICODEN does not require the proportional hazards assumption or a prespecified parametric form for the hazard function, thereby permitting flexible survival modeling. Across simulation settings with proportional or non-proportional hazards and both linear and nonlinear covariate effects, ICODEN consistently achieves satisfactory predictive accuracy and remains stable as the number of predictors increases. Applications to data from multiple phases of the Alzheimer's Disease Neuroimaging Initiative (ADNI) and to two Age-Related Eye Disease Studies (AREDS and AREDS2) for age-related macular degeneration (AMD) demonstrate ICODEN's robust prediction performance. In both applications, predicting time-to-AD or time-to-late AMD, ICODEN effectively uses hundreds to more than 1,000 SNPs and supports data-driven subgroup identification with differential progression risk profiles. These results establish ICODEN as a practical assumption-lean tool for prediction with interval-censored survival data in high-dimensional biomedical settings.

生存分析区间删失神经网络高维数据

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