arXiv:2605.21454cs.CVq-bio.QM2026-05

用生物结构原型融合病理与基因数据,提升癌症生存预测可解释性。

ProtoPathway: Biologically Structured Prototype-Pathway Fusion for Multimodal Cancer Survival Prediction

论文配图:ProtoPathway: Biologically Structured Prototype-Pathway Fusion for Multimodal Cancer Survival Prediction
图 1 · 摘自论文原文
  • 病理图像用可学习的形态原型表示,基因数据通过反应组路径图神经网络编码。
  • 跨模态注意力在原型与通路矩阵间计算,准确率优于现有方法且推理成本更低。
  • 结果可解释性强,能追溯从基因到组织的生物学路径,适合临床研究者使用。

我们提出ProtoPathway,一种设计上可解释的多模态癌症生存预测框架,通过编码器在病理和转录组两侧生成具有生物学基础的表征。病理侧采用K个可学习的形态原型,通过软分配将图像块映射为固定长度的任务自适应原型令牌,实现可变长度图像块的压缩。基因侧使用双分图神经网络,在Reactome通路层级中编码基因表达,通过共享的基因-通路图进行双向消息传递,生成反映基因及其生物学背景的通路嵌入。跨模态注意力在紧凑的原型×通路矩阵上运行,原型查询通路,建模分子程序向组织形态演化的生物学方向。由于双轴均具备任务学习的身份稳定性,注意力矩阵本身即为可解释输出,实现从基因、通路、原型到空间组织图谱的全层级推理归因。我们在五个TCGA癌种队列上评估,表现优于或相当现有方法,显著提升可解释性并降低计算成本,可解释性通过分层折叠的秩次分析得到验证。代码、模型权重、Reactome通路及统一复现所有多模态生存基线的代码库已开源:https://github.com/AmayaGS/ProtoPathway。

原文摘要 · Abstract (English)

We introduce ProtoPathway, an interpretable-by-design multimodal framework for cancer survival prediction that unifies whole slide imaging and transcriptomics through encoders producing biologically grounded representations on both sides of the fusion. On the histopathology side, $K$ learnable morphological prototypes, trained end-to-end with the survival objective, serve as the slide representation itself: patches flow into prototype tokens via soft assignment, compressing variable-length patch sets into fixed task-adaptive tokens. On the genomic side, a bipartite graph neural network encodes gene expression within the Reactome pathway hierarchy, producing pathway embeddings that reflect both constituent genes and their broader biological context through bidirectional message passing over a shared gene--pathway graph. Cross-modal attention then operates over a compact prototype $\times$ pathway matrix in which prototypes query pathways, modeling the biological direction in which molecular programs give rise to tissue morphology. Because both axes carry stable task-learned identity, the attention matrix is itself an interpretability output, yielding native inference-time attribution across the full biological hierarchy, from genes through pathways and prototypes to spatial tissue maps. We evaluate on five TCGA cancer cohorts, demonstrating competitive or superior survival prediction with substantially improved biological interpretability and reduced computational cost, with interpretability claims validated through fold-stratified rank-based population-level analysis. Our source code, model weights, and Reactome pathways, together with a unified codebase reimplementing all multimodal survival baselines under identical preprocessing and evaluation, are available at: https://github.com/AmayaGS/ProtoPathway.

癌症预测多模态融合可解释性生物通路

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