用H&E切片预测基因表达,提升跨切片稳定性与精度。
CHRep: Cross-modal Histology Representation and Post-hoc Calibration for Spatial Gene Expression Prediction

- 分两阶段:先学结构感知表征,再轻量校准增强鲁棒性。
- 在三组数据上显著提升相关性,最大增益达9.8%。
- 适合病理图像分析、基因表达预测等生物医学研究者。
空间转录组技术可实现基因的空间定位,但成本高、通量低,限制了大规模研究和临床应用。从常规苏木精-伊红(H&E)切片预测空间基因表达是一种有前景的替代方案,但在真实场景的留一滑块评估中,现有模型常受切片级外观差异和回归导致的过平滑影响,抑制了生物学有意义的变化。CHRep是一种两阶段框架,用于稳健的组织学到表达预测。训练阶段,通过联合优化相关性感知回归、对称图像-表达对齐及坐标诱导的空间拓扑正则化,学习结构感知表示。推理阶段,通过一个无需微调主干网络的轻量级校准模块,结合训练集画廊的非参数估计与幅度正则化修正模块,提升跨切片鲁棒性。不同于依赖单一预测路径的嵌入对齐或检索迁移方法,CHRep将拓扑保持表示学习与后处理校准相结合,在切片级变化下仍能实现稳定邻域检索与可控偏差修正。在三个队列中,CHRep在留一滑块评估下持续提升基因层面相关性,最大增益出现在Alex+10x。相较于HAGE,cSCC上所有基因的皮尔逊相关系数[PCC(ACG)]提升4.0%,HER2+上提升9.8%。相较于mclSTExp,Alex+10x上PCC(ACG)进一步提升39.5%,同时均方误差(MSE)和平均绝对误差(MAE)分别降低9.7%和9.0%。
原文摘要 · Abstract (English)
Spatial transcriptomics (ST) enables spatially resolved gene profiling but remains expensive and low-throughput, limiting large-cohort studies and routine clinical use. Predicting spatial gene expression from routine hematoxylin and eosin (H&E) slides is a promising alternative, yet under realistic leave-one-slide-out evaluation, existing models often suffer from slide-level appearance shifts and regression-driven over-smoothing that suppress biologically meaningful variation. CHRep is a two-phase framework for robust histology-to-expression prediction. In the training phase, CHRep learns a structure-aware representation by jointly optimizing correlation-aware regression, symmetric image-expression alignment, and coordinate-induced spatial topology regularization. In the inference phase, cross-slide robustness is improved without backbone fine-tuning through a lightweight calibration module trained on the training slides, which combines a non-parametric estimate from a training gallery with a magnitude-regularized correction module. Unlike prior embedding-alignment or retrieval-based transfer methods that rely on a single prediction route, CHRep couples topology-preserving representation learning with post-hoc calibration, enabling stable neighborhood retrieval and controlled bias correction under slide-level shifts. Across the three cohorts, CHRep consistently improves gene-wise correlation under leave-one-slide-out evaluation, with the largest gains observed on Alex+10x. Relative to HAGE, the Pearson correlation coefficient on all considered genes [PCC(ACG)] increases by 4.0% on cSCC and 9.8% on HER2+. Relative to mclSTExp, PCC(ACG) further improves by 39.5% on Alex+10x, together with 9.7% and 9.0% reductions in mean squared error (MSE) and mean absolute error (MAE), respectively.
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