arXiv:2608.16669cs.CV2026-08

通过形态概念解释癌组织图像如何预测基因表达,揭示病理与分子特征的关联。

Concept-based explanation of gene expression prediction from H&E images

论文配图:Concept-based explanation of gene expression prediction from H&E images
图 1 · 摘自论文原文
  • 结合显著性传播与概念发现,将组织形态与转录程序关联
  • 在结直肠癌数据中实现0.872的分类准确率,区分不同亚型
  • 构建基于相关性的概念图谱,适合病理与计算医学研究者

近期病理基础模型已实现从常规H&E图像准确预测空间转录组(ST)。然而,现有视觉变换器(ViT)模型的可解释性方法多局限于局部热图,难以揭示形态学概念对预测的贡献。本文提出一种可解释框架,融合显著性传播与概念发现,建立转录程序与组织形态之间的联系。我们开发了基于ViT的虚拟ST框架,结合ViT感知的逐层显著性传播与松弛的典型拓扑K稀疏自编码器概念发现方法。该方法同时提供局部解释和全局形态模式洞察。在HEST-1k队列的结直肠癌ST数据上应用,并在TCGA COAD中评估泛化能力。模型准确预测临床相关的ST标志物及伴随分子表型。实测与预测基因表达显示iCMS2和iCMS3亚型存在显著空间异质性,空间分辨与聚合分类的加权F1分数分别为0.872和0.819(TCGA COAD为0.770),且均能分层患者预后。此外,框架建立了一个基于相关性的概念图谱,连接分子表型与组织病理表示。激活与显著性生成的概念对比表明,显著性更直接反映形态与下游预测的关系。本工作建立了概念基础的时空预测解释通用策略,框架可广泛应用于各类基于ViT的病理模型。

原文摘要 · Abstract (English)

Recent advances in pathology foundation models have enabled accurate prediction of spatial transcriptomics (ST) from routine H&E images. However, existing explainability methods for vision transformer (ViT)-based models are largely limited to local heatmaps and do not reveal how morphological concepts contribute to ST predictions. Here, we introduce an explainable framework that combines relevance propagation and concept discovery to link transcriptional programs to tissue morphology. We developed a ViT-based framework for virtual ST from H&E images that combines ViT-aware layer-wise relevance propagation with relaxed archetypal TopK sparse autoencoder-based concept discovery. This approach provides both local explanations and global insights into the morphological patterns associated with transcriptional programs. We applied the framework to colorectal cancer ST data from the HEST-1k cohort and evaluated its generalizability in TCGA COAD. Our architecture accurately predicts clinically relevant ST signatures and accompanying molecular phenotypes. Measured and predicted gene expression profiles reveal substantial spatial heterogeneity of the colorectal cancer subtypes iCMS2 and iCMS3 across a large number of samples. Spatially resolved and aggregated iCMS classification achieve weighted F1 scores of 0.872 and 0.819 (0.770 in TCGA COAD), respectively, and both stratify patient outcome. Beyond prediction, our framework establishes a relevance-based concept atlas linking molecular phenotypes to histopathological representations. Comparison of activation- with relevance-derived concepts demonstrates that relevances provide a more direct link between tissue morphology and downstream predictions. We establish a general strategy for concept-based explanation of spatial prediction, and our framework is readily applicable to a broad range of ViT-based pathology models.

病理分析基因预测可解释性视觉模型

Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。