用H&E切片一键生成空间转录组,速度快且精度高。
DriftST: One-Step Generative Inference of Spatial Transcriptomics from H\&E Histology

- 基于细胞漂移机制,实现从组织图像到基因表达的一步生成。
- 在多种组织和分辨率下均达到当前最佳性能,尤其在细胞级精度上提升显著。
- 同时捕捉基因间关系与重要性差异,适用于不同尺度的数据分析。
空间转录组可保留基因表达的空间信息,但成本高、通量低,导致公开数据集规模有限。从广泛可用的苏木精-伊红(H&E)染色切片推断基因表达是一种低成本替代方案。然而,现有方法存在诸多局限:回归方法过度平滑至条件均值,生成方法虽准确但需多步推断;多数方法将基因视为独立且等价,忽略基因间依赖关系与重要性差异;且多数仅针对单一分辨率(如点级或细胞级)。为此,我们提出DriftST,一个统一框架,可直接从H&E图像推断空间分辨基因表达。DriftST基于细胞漂移生成模型,学习从组织图像条件源到表达分布的直接漂移路径,兼具生成能力与高效的一步推断。为建模基因结构,引入STransformer,结合共表达注意力模块捕捉基因间依赖,并通过基因残差门控制不同基因的重要性。该框架采用通用基因面板表示,可在同一框架内处理点级与细胞级数据。跨多种组织与平台的大量实验表明,DriftST在两类分辨率下均达到当前最优表现。
原文摘要 · Abstract (English)
Spatial Transcriptomics (ST) measures gene expression while preserving spatial context, but its high cost and low throughput leave public datasets small. Inferring expression directly from widely available Hematoxylin and Eosin (H&E) stained histology offers a cost-effective alternative. However, existing approaches face several limitations: regression methods over-smooth toward the conditional mean, while generative methods are faithful but require slow multi-step inference; most methods treat genes as independent and equally important, ignoring inter-gene dependencies and heterogeneous gene informativeness; and most are tailored to a single resolution, either spot-level or cell-level. To address these issues, we propose DriftST, a unified framework for inferring spatially resolved gene expression from H&E images. DriftST builds on a Cellular Drifting generative model that learns a direct drift from a histology-conditioned source to the expression distribution, retaining generative expressiveness while enabling efficient one-step generation. To capture gene structure, we introduce the STransformer, which combines a co-expression attention module for inter-gene dependencies with a gene residual gate for differential gene importance. Operating on a generic gene-panel representation, DriftST applies directly to both spot-level and cell-level data in one framework, and extensive experiments across diverse tissues and platforms show that it achieves state-of-the-art performance at both resolutions.
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