空间转录组迭代层次聚类（stIHC）：一种识别空间基因共表达模块的新方法
Spatial Transcriptomics Iterative Hierarchical Clustering (stIHC): A Novel Method for Identifying Spatial Gene Co-Expression Modules
AI总结：
针对现有空间可变基因聚类方法难检测稀有空间表达模式的问题，提出空间转录组迭代层次聚类法stIHC，经多模拟和多技术数据集验证性能优于主流方法，且模块基因功能一致，可用于解析基因表达空间组织与复杂组织功能结构。
摘要：
空间转录组技术的最新进展使研究人员能够在保留组织内空间信息的同时，同时测量数百到数千个基因的RNA表达水平，为空间基因表达模式、组织构建和基因功能研究提供关键见解。然而，现有将空间可变基因（SVG）聚类为共表达模块的方法往往无法检测到稀有或独特的空间表达模式。为解决这一问题，我们提出了空间转录组迭代层次聚类（stIHC），这是一种将SVG聚类为共表达模块的新方法，共表达模块代表具有共同空间表达模式的基因组。通过三组模拟实验，以及对来自10x Visium、10x Xenium和Spatial Transcriptomics等技术的空间转录组数据集的应用，stIHC的表现优于主流SVG检测方法所采用的聚类方案，包括SPARK、SPARK-X、MERINGUE和SpatialDE。基因本体富集分析证实，每个模块内的基因具有一致的生物学功能，验证了空间共表达的功能相关性。stIHC在具有不同基因数量和空间分辨率的技术间均表现出稳健性，为解析基因表达的空间组织和复杂组织的功能结构提供了有力工具。
英文摘要：
Recent advancements in spatial transcriptomics technologies allow researchers to simultaneously measure RNA expression levels for hundreds to thousands of genes while preserving spatial information within tissues, providing critical insights into spatial gene expression patterns, tissue organization, and gene functionality. However, existing methods for clustering spatially variable genes (SVGs) into co-expression modules often fail to detect rare or unique spatial expression patterns. To address this, we present spatial transcriptomics iterative hierarchical clustering (stIHC), a novel method for clustering SVGs into co-expression modules, representing groups of genes with shared spatial expression patterns. Through three simulations and applications to spatial transcriptomics datasets from technologies such as 10x Visium, 10x Xenium, and Spatial Transcriptomics, stIHC outperforms clustering approaches used by popular SVG detection methods, including SPARK, SPARK-X, MERINGUE, and SpatialDE. Gene Ontology enrichment analysis confirms that genes within each module share consistent biological functions, supporting the functional relevance of spatial co-expression. Robust across technologies with varying gene numbers and spatial resolution, stIHC provides a powerful tool for decoding the spatial organization of gene expression and the functional structure of complex tissues.
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