arXiv:2604.06267cs.LGcs.AI2026-04

通过优化潜在空间正则化,提升多组学生存风险建模的稳定性与区分度。

MO-RiskVAE: A Multi-Omics Variational Autoencoder for Survival Risk Modeling in Multiple MyelomaMO-RiskVAE

  • 系统对比不同潜在空间正则化策略对生存预测的影响。
  • 适度放松KL正则化显著提升生存判别能力,混合连续-离散结构增强风险排序。
  • 模型无需额外监督即可稳定改进风险分层,适合临床预后研究。

多模态变分自编码器(VAEs)在整合异构组学与临床数据方面展现出强大潜力,用于多发性骨髓瘤的生存风险建模。然而,在生存监督下训练时,标准潜在空间正则化策略常无法保留预后相关变异,导致表示不稳定或过度约束。尽管已有多种改进方法,但其潜在空间设计的关键因素仍不明确。本文在统一扩展的MyeVAE框架下,系统研究了多模态生存预测中的潜在空间建模选择。通过在相同架构和优化协议下,独立考察正则化强度、后验几何与潜在空间结构,发现生存驱动训练主要受潜在正则化幅度与结构影响,而非具体散度形式。特别是,适度放松KL正则化能持续提升生存判别能力,而MMD与HSIC等替代散度机制在未适当缩放时收益有限。进一步表明,合理设计潜在空间可增强学习表征与生存风险梯度的一致性。基于Gumbel-Softmax的混合连续-离散结构虽未能稳定发现离散亚型,但显著改善了连续潜空间中的全局风险排序。基于此,我们提出稳健的多模态生存模型MO-RiskVAE,无需额外监督或复杂训练技巧,即能持续优于原始MyeVAE。

原文摘要 · Abstract (English)

Multimodal variational autoencoders (VAEs) have emerged as a powerful framework for survival risk modeling in multiple myeloma by integrating heterogeneous omics and clinical data. However, when trained under survival supervision, standard latent regularization strategies often fail to preserve prognostically relevant variation, leading to unstable or overly constrained representations. Despite numerous proposed variants, it remains unclear which aspects of latent design fundamentally govern performance in this setting. In this work, we conduct a controlled investigation of latent modeling choices for multimodal survival prediction within a unified extension of the MyeVAE framework. By systematically isolating regularization scale, posterior geometry, and latent space structure under identical architectures and optimization protocols, we show that survival-driven training is primarily sensitive to the magnitude and structure of latent regularization rather than the specific divergence formulation. In particular, moderate relaxation of KL regularization consistently improves survival discrimination, while alternative divergence mechanisms such as MMD and HSIC provide limited benefit without appropriate scaling. We further demonstrate that structuring the latent space can improve alignment between learned representations and survival risk gradients. A hybrid continuous--discrete formulation based on Gumbel--Softmax enhances global risk ordering in the continuous latent subspace, even though stable discrete subtype discovery does not emerge under survival supervision. Guided by these findings, we instantiate a robust multimodal survival model, termed MO-RiskVAE, which consistently improves risk stratification over the original MyeVAE without introducing additional supervision or complex training heuristics.

生存分析多组学变分自编码器风险分层

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