通过空间邻近与表达相似性混合,提升单细胞空间转录组补全精度。
SNR-ST-Mix: Sample-specific Neighborhood Regression Mixup for Augmented Spatial Transcriptomics Imputation with Deep Neural Network

- 基于邻域空间与表达相似性的自适应混合策略
- 在多种组织上显著优于传统增强方法,无需修改模型
- 适合空间转录组回归任务,尤其适用于样本少的情况
空间转录组技术可测量组织背景下的基因表达,但数据常受噪声、低分辨率和稀疏采样限制,影响精细空间结构的恢复。深度神经网络已用于从组织图像中进行表达补全,但其性能受限于样本量小及缺乏生物合理增强。现有增强方法多针对分类任务,忽视空间与转录组关系,导致生物学上不合理的插值,降低预测效果。为此,我们提出SNR-ST-Mix,一种专为空间转录组设计的几何与表达感知增强框架。该方法将混合限制在某点的k个最近邻,并根据表达相似性自适应加权插值系数,生成既保留局部生物结构又保证空间平滑的合成样本。双重约束使合成样本扩展有效训练流形,提升泛化能力与预测稳定性。在多种组织类型的实验中,SNR-ST-Mix持续优于传统增强方法,且无需模型结构调整或额外计算开销。结论:该方法提供了一种有效且生物合理的空间转录组回归增强策略,通过显式利用空间几何与表达相似性,扩大训练流形,提升预测性能而不增加模型复杂度。
原文摘要 · Abstract (English)
Purpose: Spatial transcriptomics (ST) enables gene expression measurements within the tissue context. However, these measurements are often noisy, low-resolution, and sparsely sampled, which limits the recovery of fine spatial structure. Deep neural networks have become powerful tools for expression imputation from histology, but their performance remains constrained by limited sample sizes and a lack of biologically informed augmentation. Most of the existing augmentation strategies for learning are designed for classification tasks rather than regression, which neglect spatial and transcriptomic relationships, leading to biologically implausible interpolations that hinder prediction performance. Approach: To address these limitations, we propose SNR-ST-Mix, a geometry- and expression-aware data augmentation framework designed specifically for ST data. It constrains mixing to a spot's k-nearest spatial neighbors and adaptively weights interpolation coefficients based on expression similarity, generating augmented samples that preserve local biological structure while ensuring spatial smoothness. This dual conditioning yields synthetic examples that expand the effective training manifold, promote generalization, and enhance prediction stability under sample-specific training. Results: Extensive experiments with various tissue types demonstrate that SNR-ST-Mix consistently outperforms conventional augmentation methods without requiring architectural changes or additional computation. Conclusions: SNR-ST-Mix provides an effective and biologically principled augmentation strategy for spatial transcriptomics regression tasks. By explicitly leveraging spatial geometry and transcriptomic similarity, it expands the effective training manifold and improves predictive performance without increasing model complexity.
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