用对比自编码器融合多组学数据,提升肺癌生存预测在数据缺失下的稳定性。
A Contrastive Variational AutoEncoder for NSCLC Survival Prediction with Missing Modalities
- 设计模态特定编码器与门控融合瓶颈,处理不同数据来源的不确定性。
- 在TCGA-LUAD和LUSC数据集上,生存预测准确率优于现有模型,缺失数据下表现更稳健。
- 揭示了多模态融合并非总有益,提供可解释性指导,适合临床医疗AI研究者。
非小细胞肺癌(NSCLC)生存预测因个体预后特征差异大而困难。整合全切片图像、批量转录组和DNA甲基化数据可提供诊断时患者状况的互补视角,但真实临床数据常存在大量缺失,部分患者甚至缺少完整模态。当前先进模型依赖可用数据构建患者表征或使用生成模型推断缺失模态,但在严重缺失情况下鲁棒性不足。本文提出多模态对比变分自编码器(MCVAE):模态特定变分编码器捕捉各数据源的不确定性,融合瓶颈引入学习型门控机制以标准化当前模态的贡献。采用联合生存损失与重建损失的多任务目标正则化患者表征,并引入跨模态对比损失,在潜在空间中强制对齐不同模态。训练中应用随机模态掩码,提升对任意缺失模式的鲁棒性。在TCGA-LUAD(n=475)和TCGA-LUSC(n=446)数据集上的广泛评估表明,本方法在预测疾病特异性生存(DSS)方面有效,且在严重缺失场景下优于两种前沿模型。最后通过测试所有模态子集,澄清多模态集成并非始终有益。
原文摘要 · Abstract (English)
Predicting survival outcomes for non-small cell lung cancer (NSCLC) patients is challenging due to the different individual prognostic features. This task can benefit from the integration of whole-slide images, bulk transcriptomics, and DNA methylation, which offer complementary views of the patient's condition at diagnosis. However, real-world clinical datasets are often incomplete, with entire modalities missing for a significant fraction of patients. State-of-the-art models rely on available data to create patient-level representations or use generative models to infer missing modalities, but they lack robustness in cases of severe missingness. We propose a Multimodal Contrastive Variational AutoEncoder (MCVAE) to address this issue: modality-specific variational encoders capture the uncertainty in each data source, and a fusion bottleneck with learned gating mechanisms is introduced to normalize the contributions from present modalities. We propose a multi-task objective that combines survival loss and reconstruction loss to regularize patient representations, along with a cross-modal contrastive loss that enforces cross-modal alignment in the latent space. During training, we apply stochastic modality masking to improve the robustness to arbitrary missingness patterns. Extensive evaluations on the TCGA-LUAD (n=475) and TCGA-LUSC (n=446) datasets demonstrate the efficacy of our approach in predicting disease-specific survival (DSS) and its robustness to severe missingness scenarios compared to two state-of-the-art models. Finally, we bring some clarifications on multimodal integration by testing our model on all subsets of modalities, finding that integration is not always beneficial to the task.
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