融合病理图像与空间转录组数据,提升生存预测可解释性
Prototype-driven fusion of pathology and spatial transcriptomics for interpretable survival prediction
- 通过多层级专家架构学习跨模态原型,实现图像与分子数据协同建模
- 在五项生存指标上表现优于或接近领先方法,准确率显著提升
- 可生成生物可解释的分子风险分解,适合临床研究与精准医疗应用
全切片图像(WSI)可通过多实例学习(MIL)实现弱监督预后建模。空间转录组学(ST)保留原位基因表达信息,提供补充形态学的空间分子背景。随着配对的WSI-ST队列扩展至人群规模,整合其互补的空间信号进行预后预测变得至关重要;然而,针对该范式的系统性跨模态融合策略仍有限。为此,我们提出PathoSpatial,一个可解释的端到端框架,整合共注册的WSI与ST数据,学习空间感知的预后表征。PathoSpatial在多层级专家架构中采用任务引导的原型学习,自适应协调模态内无监督发现与模态间有监督聚合。设计上,它显著增强可解释性并保持判别能力。我们在三阴性乳腺癌队列上评估PathoSpatial,涵盖配对的ST与WSI数据。该方法在五个生存终点上表现强劲且一致,性能优于或媲美领先的单模态与多模态方法。PathoSpatial天然支持事后原型解释与分子风险分解,提供定量、生物学合理的解释,识别潜在预后因子。我们以该工作为概念验证,展示适用于空间组学-病理融合的可扩展、可解释多模态学习。
原文摘要 · Abstract (English)
Whole slide images (WSIs) enable weakly supervised prognostic modeling via multiple instance learning (MIL). Spatial transcriptomics (ST) preserves in situ gene expression, providing a spatial molecular context that complements morphology. As paired WSI-ST cohorts scale to population level, leveraging their complementary spatial signals for prognosis becomes crucial; however, principled cross-modal fusion strategies remain limited for this paradigm. To this end, we introduce PathoSpatial, an interpretable end-to-end framework integrating co-registered WSIs and ST to learn spatially informed prognostic representations. PathoSpatial uses task-guided prototype learning within a multi-level experts architecture, adaptively orchestrating unsupervised within-modality discovery with supervised cross-modal aggregation. By design, PathoSpatial substantially strengthens interpretability while maintaining discriminative ability. We evaluate PathoSpatial on a triple-negative breast cancer cohort with paired ST and WSIs. PathoSpatial delivers strong and consistent performance across five survival endpoints, achieving superior or comparable performance to leading unimodal and multimodal methods. PathoSpatial inherently enables post-hoc prototype interpretation and molecular risk decomposition, providing quantitative, biologically grounded explanations, highlighting candidate prognostic factors. We present PathoSpatial as a proof-of-concept for scalable and interpretable multimodal learning for spatial omics-pathology fusion.
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