用六边形结构优化基因表达预测,更准更保真。
HEXST: Hexagonal Shifted-Window Transformer for Spatial Transcriptomics Gene Expression Prediction

- 基于六边形采样设计注意力机制,适配真实数据布局。
- 在7个数据集上超越现有模型,保留基因空间异质性。
- 结合对比损失与单细胞先验,提升基因特异性表达差异。
空间转录组学可在组织切片中实现基因表达的空间解析,但成本高、通量低,限制了大规模应用。为推动其进入常规实践,近期计算方法尝试从常见的苏木精-伊红染色病理切片直接推断空间基因表达。然而,多数现有模型假设笛卡尔或无几何结构的局部性,忽略了广泛使用的点阵平台的六边形采样特性;且点式回归目标常导致表达图过度平滑,掩盖基因特异性空间异质性。为此,我们提出HEXST——一种面向空间基因表达预测的几何对齐Transformer。HEXST直接在六边形点坐标上操作,通过定制的移位窗口注意力机制和六边形旋转位置编码,实现高效的局部到全局上下文建模。为增强基因级空间对比度,HEXST在训练中融合点式回归与对比敏感的差分目标,并引入预训练单细胞基础模型提供的转录组先验。在七个空间转录组数据集上,HEXST持续优于现有最优模型,提供准确且稳健的空间基因表达预测,同时保持基因级对比度与空间异质性。
原文摘要 · Abstract (English)
Spatial transcriptomics offers spatially resolved gene expression profiling within tissue sections, but its cost and limited throughput hinder large-scale deployment. To extend this capability to routine practice, recent computational methods aim to infer spatial gene expression directly from ubiquitous hematoxylin and eosin-stained histology slides. However, most existing models assume Cartesian or geometry-agnostic locality, despite the hexagonal sampling of widely used spot-array platforms, and point-wise regression objectives often yield over-smoothed gene expression profiles, obscuring gene-specific spatial heterogeneity. To address these, we propose HEXST, a geometry-aligned Transformer for spatial gene expression prediction from histology. HEXST operates directly on hexagonal spot coordinates to enable efficient local-to-global contextual modeling via tailored shifted-window attention mechanism and hexagonal rotary positional encoding. To enhance gene-wise spatial contrast, HEXST complements point-wise regression with a contrast-sensitive differential objective and transcriptomic priors from a pretrained single-cell foundation model during training. Across seven spatial transcriptomics datasets, HEXST consistently outperforms state-of-the-art models, providing accurate and robust spatial gene expression predictions while preserving gene-wise contrast and spatial heterogeneity.
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