arXiv:2608.14710cs.CVcs.AI2026-08

用组织层级结构指导从病理图像预测基因表达,提升空间转录组精度。

Path2ST: Hierarchical Cell-Tissue Grounded Cross-Modal Translation for Spatial Transcriptomics

论文配图:Path2ST: Hierarchical Cell-Tissue Grounded Cross-Modal Translation for Spatial Transcriptomics
图 1 · 摘自论文原文
  • 基于细胞-组织层级构建条件信号,融合显式与隐式特征。
  • 分层自回归生成实现从粗到细的基因表达合成,保持生物一致性。
  • 新损失函数兼顾表达顺序、爆发模式和细胞类型语义对齐,适合医学影像分析者。

从苏木精-伊红(H&E)染色图像预测空间基因表达,可为昂贵的空间转录组学提供经济替代方案。然而,现有方法将H&E图像视为通用视觉输入,忽略了其内在生物学层次结构——空间组织的细胞类型共同构成功能性的组织微环境,调控局部基因表达程序。为此,我们提出路径2ST(Path2ST),一种分层细胞-组织引导的自回归跨模态翻译框架,包含三个核心组件:(i) 分层细胞-组织条件机制,融合显式与隐式细胞特征及组织级语义表示,构建分层条件信号;(ii) 针对分层语义词表的尺度自适应自回归生成过程,实现从粗到细、生物一致的表达合成;(iii) 全谱损失(SpectraLoss),联合约束序数保真度、建模转录爆发,并对齐语义结构与细胞类型。在三个数据集上的实验表明,该方法达到最先进性能,生成高度准确且空间一致的转录组图谱。相关代码已开源。

原文摘要 · Abstract (English)

Predicting spatial gene expression from hematoxylin and eosin (H\&E)-stained images offers a cost-effective alternative to spatial transcriptomics (ST). However, existing methods treat H\&E images as generic visual inputs and ignore their intrinsic biological hierarchy, where spatially organized cell types collectively form functional tissue microenvironments that govern local gene expression programs. To bridge this gap, we formulate H\&E-to-ST prediction as a cross-modal semantic translation task and propose Path2ST, a hierarchically grounded autoregressive framework featuring three key components: (i) a Hierarchical Cell-Tissue Conditioning mechanism that fuses explicit and implicit cellular features with tissue-level semantic representations to construct hierarchical conditioning signals; (ii) a Scale-Adaptive Autoregressive Generation process over a hierarchical semantic vocabulary, enabling coarse-to-fine, biologically consistent expression synthesis; and (iii) SpectraLoss, a full-spectrum objective that jointly enforces ordinal fidelity, models transcriptional bursts, and aligns semantic structures with cell types. Extensive experiments on three datasets demonstrate state-of-the-art performance, validating that Path2ST generates highly accurate and spatially coherent transcriptomic profiles. The related code is released at https://github.com/RuochenLiu23/Path2ST.

空间转录组跨模态生成病理图像自回归模型

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