用通路知识增强深度模型,提升癌症多组学整合的可解释性与预测力。
Biologically Informed Deep Neural Networks for Multi-Omic Integration, Pathway Activity Inference and Risk Stratification in Cancer

- 通过通路约束架构嵌入生物学先验,兼顾模型表达力与可解释性。
- 在乳腺癌数据上实现生存预测与亚型分类,基因/蛋白/miRNA层贡献最显著。
- 可视化特征空间揭示临床相关性,为多组学整合提供实操指南。
整合复杂多组学数据面临重大挑战。现有方法常在模型可解释性与表征能力间权衡,多数依赖事后解释或使用线性模型而忽略复杂交互。我们提出通路活性自编码器框架,通过通路引导的结构约束嵌入先验知识,在保持强表征能力的同时提升可解释性。该框架应用于乳腺癌场景,在生存预测与亚型分类任务中均表现出整合优势。分析各组学层对最终任务的影响发现,基因、蛋白质及miRNA表达层贡献最强。重复性研究表明,虽然丢弃法提升模型鲁棒性,但过度正则化会降低预测性能。对学习特征空间的可视化进一步揭示了框架内在透明性与临床相关性。结果强调多组学整合的价值,并明确各组学层的作用,为本框架内的整合提供实用指导。总体而言,我们的通路活性自编码器生成具有生物学意义且可直接转化为临床洞察的优越潜在表示。
原文摘要 · Abstract (English)
Integrating complex, multi-omics data presents significant challenges. Existing approaches often face a trade-off between model interpretability and representational capacity, with most either relying on post-hoc interpretation or use linear models that may overlook complex interactions. We report Pathway Activity Autoencoders for the multi-omics setting, which embed prior knowledge via pathway-informed architectural constraints, fostering interpretability, while preserving representational power. Our multi-omic framework is applied in the context of breast cancer and is evaluated in survival prediction and subtype classification with results indicating a positive effect of integration. We conduct analysis of individual omics layer impact on end-task performance, revealing that gene, protein, and microRNA expression layers provide the strongest contribution. Repeatability studies indicate that, while dropout improves model robustness and consistency, excessive regularisation can reduce predictive performance. Finally, visualizations of the learned feature space illustrate the framework's intrinsic transparency and clinical relevance. The results underscore the value of multi-omic integration and delineate the impact of individual omics layers, establishing practical guidelines for integration within our framework. Overall, our pathway activity autoencoder frameworks yield superior latent representations that are biologically meaningful and are directly translatable into clinically relevant insights.
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