# Spatial transcriptomics iterative hierarchical clustering (stIHC): A novel method for identifying spatial gene co‐expression modules

## TL;DR

This paper introduces stIHC, a new method for clustering genes in spatial transcriptomics data to better identify spatial gene expression patterns and their biological functions.

## Contribution

The novel stIHC method improves detection of spatial gene co-expression modules compared to existing approaches.

## Key findings

- stIHC outperforms existing methods like SPARK and SpatialDE in clustering spatially variable genes.
- Gene ontology analysis shows that stIHC modules are biologically relevant and functionally consistent.
- The method is robust across different spatial transcriptomics technologies and resolutions.

## Abstract

Recent advancements in spatial transcriptomics (ST) 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 ST 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.