融合转录调控网络的空间域识别方法

    Identifying Spatial Domains by Integrating Transcriptional Regulatory Networks

    • 摘要: 随着空间转录组 (Spatial Transcriptomics, ST) 技术的快速发展,研究者能够同时获取组织切片的基因表达与空间位置信息,从而解析组织微环境及其异质性。空间域识别是ST分析的核心任务,但现有空间域识别方法在处理高维稀疏数据时对空间结构与生物功能信息的联合利用仍不足,限制了对复杂组织区域的可解性刻画。为此,本文提出了一种融合转录调控信息的多视图图卷积网络 (TF-GCN) :基于SCENIC构建调控活性视图,并与空间邻接视图联合建模,通过共卷积对齐与注意力融合实现多视图自适应整合。在公开数据集DLPFC、 BRCA等的实验表明,TF-GCN在聚类准确性与鲁棒性方面优于对比方法;此外,在STARmap高分辨率数据及无人工标注乳腺癌数据上进一步验证了方法的泛化性。消融实验与注意力权重分析表明,共卷积、注意力融合与正则约束均对性能提升有贡献,且权重分配可随组织异质性自适应调整。综上,TF-GCN能更充分融合空间信息与转录调控信息,提升对复杂组织结构的解析能力。

       

      Abstract: The rapid development of Spatial Transcriptomics (ST) has enabled the simultaneous acquisition of gene expression profiles and spatial locations from tissue sections, facilitating the characterization of tissue microenvironments and heterogeneity. Spatial domain identification is a core task in ST analysis. However, existing methods still underutilize the joint exploitation of spatial structure and biological functional signals when handling high-dimensional and sparse data, which limits their interpretable ability in delineating complex tissue regions. To address this, we propose TF-GCN, a multi-view graph convolutional network that integrates transcriptional regulatory information. Specifically, we construct a regulatory activity view using SCENIC and jointly model it with a spatial adjacency view, achieving adaptive multi-view integration via co-convolution alignment and attention-based fusion. Experimental results on public datasets such as DLPFC and BRCA demonstrate that TF-GCN outperforms baseline methods in clustering accuracy and robustness. Moreover, we further validate its generalizability on high-resolution STARmap data and an unlabeled breast cancer dataset. Ablation studies and attention-weight analyses indicate that co-convolution, attention fusion, and regularization each contribute substantially to performance improvements, and that the learned weights adapt to tissue heterogeneity. Overall, TF-GCN more effectively fuses spatial information with transcriptional regulatory signals, improving the characterization of complex tissue architectures.

       

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