arXiv:2607.24364cs.CV2026-07

用组织上下文动态调整基因先验,提升病理切片预测基因表达精度。

HistoGPA: A Context-Conditioned Gene-Prior Attention Framework for Histology-Based Spatial Gene Expression Prediction

论文配图:HistoGPA: A Context-Conditioned Gene-Prior Attention Framework for Histology-Based Spatial Gene Expression Prediction
图 1 · 摘自论文原文
  • 通过双路径架构融合局部形态与全局上下文,动态调节基因先验信息。
  • 在10种癌症数据上,对前50和前1500高变基因的预测相关性均最优。
  • 特别适合需要精准空间基因表达重建的肿瘤研究与多组学整合场景。

从常规苏木精-伊红(H&E)图像预测空间基因表达,为实验性空间转录组学提供实用补充。现有方法多关注局部或多层次视觉特征,常将预训练基因表征视为固定先验,但局部形态解释与基因先验的相关性依赖于组织上下文。我们提出HistoGPA,一种上下文感知的基因先验注意力框架,采用共享的全片层表示,在两条并行路径中分别调制局部形态特征,并通过交叉注意力条件化预训练基因嵌入以检索基因先验信息。该设计使每个空间位置可基于其局部形态、位置及全片上下文,获取适配的基因先验信息。在HEST-1k数据集的10种癌症类型中,HistoGPA在相同评估协议下,对前50和前1500个高变基因集的宏平均基因级皮尔逊相关系数均优于对比方法。附加分析显示,HistoGPA更准确恢复癌相关基因的空间表达模式,且由预测与真实表达谱独立聚类所得结果一致性更高。这些发现支持一种依赖上下文的组织到表达预测范式,即局部形态表示与基因先验应共同适应整体组织上下文。

原文摘要 · Abstract (English)

Predicting spatial gene expression from routine hematoxylin and eosin (H&E) images provides a practical complement to experimental spatial transcriptomics. Existing approaches focus on local or multi-scale visual features and often treat pretrained gene representations as fixed priors, although the interpretation of local morphology and the relevance of gene priors depend on tissue context. We propose HistoGPA, a context-conditioned gene-prior attention framework that uses a shared slide-level representation in two parallel pathways: one modulates local morphological features, whereas the other conditions pretrained gene embeddings and retrieves gene-prior information through cross-attention. This design enables each spatial location to retrieve context-adapted gene-prior information using its local morphology, position, and slide context. Across ten cancer types in HEST-1k, HistoGPA achieves the highest macro-averaged gene-wise Pearson correlation coefficient among the compared methods under the same evaluation protocol for both the top-50 and top-1,500 highly variable gene sets. Additional analyses show that HistoGPA better recovers the spatial expression patterns of cancer-associated genes and yields greater agreement between clusters derived independently from predicted and ground-truth expression profiles. Together, these findings motivate a context-dependent view of histology-to-expression prediction, in which local morphological representations and gene priors are jointly adapted to the broader tissue context.

空间转录组病理图像基因表达预测注意力机制

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