Zhu Juntong, Wang Daoyuan, Chen Siqi, Meng Lili, Long Yahui, Liang Cheng
School of Information Science and Engineering, Shandong Normal University, Jinan, 250014, China.
School of Computer Science and Engineering, Central South University, Changsha, 410083, China.
Interdiscip Sci. 2025 Jun 26. doi: 10.1007/s12539-025-00728-0.
Recent advancements in spatial transcriptomics (ST) technologies have greatly revolutionized our understanding of tissue heterogeneity and cellular functions. However, popular ST, such as 10x Visium, still fall short in achieving true single-cell resolution, underscoring an urgent need for in-silico methods that can accurately resolve cell type composition within ST data. While several methods have been proposed, most rely solely on gene expression profiles, often neglecting spatial context, which results in suboptimal performance. Additionally, many deconvolution methods dependent on scRNA-seq data fail to align the distribution of ST and scRNA-seq reference data, consequently affecting the accuracy of cell type mapping. In this study, we propose stGNN, a novel spatially-informed graph learning framework powered by statistical modeling for resolving fine-grained cell type compositions in ST. To capture comprehensive features, we develop a dual encoding module, utilizing both a graph convolutional network (GCN) and an auto-encoder to learn spatial and non-spatial representations respectively. Following that, we further design an adaptive attention mechanism to integrate these representations layer-by-layer, capturing multi-scale spatial structures from low to high order and thus improving representation learning. Additionally, for model training, we adopt a negative log-likelihood loss function that aligns the distribution of ST data with scRNA-seq (or snRNA-seq) reference data, enhancing the accuracy of cell type proportion prediction in ST. To assess the performance of stGNN, we applied our proposed model to six ST datasets from various platforms, including 10x Visium, Slide-seqV2, and Visium HD, for cell type proportion estimation. Our results demonstrate that stGNN consistently outperforms seven state-of-the-art methods. Notably, when applied to mouse brain tissues, stGNN successfully resolves clear cortical layers at a high resolution. Additionally, we show that stGNN is able to effectively resolve ST at different resolutions. In summary, stGNN provides a powerful framework for analyzing the spatial distribution of diverse cell populations in complex tissue structures. stGNN's code is openly shared on https://github.com/LiangSDNULab/stGNN .
空间转录组学(ST)技术的最新进展极大地革新了我们对组织异质性和细胞功能的理解。然而,诸如10x Visium等流行的ST技术在实现真正的单细胞分辨率方面仍有不足,这凸显了对能够准确解析ST数据中细胞类型组成的计算机方法的迫切需求。虽然已经提出了几种方法,但大多数仅依赖基因表达谱,往往忽略了空间背景,导致性能欠佳。此外,许多依赖scRNA-seq数据的反卷积方法未能使ST和scRNA-seq参考数据的分布对齐,从而影响细胞类型映射的准确性。在本研究中,我们提出了stGNN,这是一种由统计建模驱动的新型空间信息图学习框架,用于解析ST中的细粒度细胞类型组成。为了捕获综合特征,我们开发了一个双编码模块,利用图卷积网络(GCN)和自动编码器分别学习空间和非空间表示。在此之后,我们进一步设计了一种自适应注意力机制,逐层整合这些表示,从低阶到高阶捕获多尺度空间结构,从而改进表示学习。此外,对于模型训练,我们采用负对数似然损失函数,使ST数据的分布与scRNA-seq(或snRNA-seq)参考数据对齐,提高ST中细胞类型比例预测的准确性。为了评估stGNN的性能,我们将我们提出的模型应用于来自各种平台的六个ST数据集,包括10x Visium、Slide-seqV2和Visium HD,用于细胞类型比例估计。我们的结果表明,stGNN始终优于七种先进方法。值得注意的是,当应用于小鼠脑组织时,stGNN成功地以高分辨率解析出清晰的皮质层。此外,我们表明stGNN能够有效地解析不同分辨率下的ST。总之,stGNN为分析复杂组织结构中不同细胞群体的空间分布提供了一个强大的框架。stGNN的代码在https://github.com/LiangSDNULab/stGNN上公开共享。
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