Spatial Transcriptomics Iterative Hierarchical Clustering (stIHC): A Novel Method for Identifying Spatial Gene Co-Expression Modules

TL;DR

stIHC is a new iterative hierarchical clustering method that effectively identifies spatial gene co-expression modules in spatial transcriptomics data, outperforming existing approaches and revealing biologically relevant gene groups.

Contribution

The paper introduces stIHC, a novel clustering method that improves detection of spatial gene modules, especially rare patterns, across multiple spatial transcriptomics technologies.

Findings

stIHC outperforms existing clustering methods in simulations and real datasets.

Gene modules identified by stIHC show consistent biological functions.

Method is robust across different technologies and resolutions.

Abstract

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.