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bioRxiv · 10.1101/2025.06.30.662268

DESpace2: detection of differential spatial patterns in spatial omics data

Cai, P.·Robinson, M. D.·Tiberi, S.
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Abstract

Spatially resolved transcriptomics (SRT) enables the investigation of mRNA expression in a spatial context. While several SRT analysis frameworks have been developed, the vast majority of them focus on analyzing individual samples, and do not allow for comparisons of spatial gene expression patterns across experimental conditions, such as healthy vs. diseased states. Here, we present an approach to identify so-called differential spatial patterns (DSP), i.e., genes that exhibit changes in spatial expression between groups of samples across conditions. Our framework processes diverse SRT data types and detects DSP by performing differential gene expression testing across conditions. Notably, this comparison is not currently available in any other spatial omics method. In addition to detecting DSP across conditions, our framework includes two key features. First, it can identify tissue regions where expression changes across conditions. Second, it can detect spatial gene expression pattern changes across more than two experimental conditions, with flexible models. With ad hoc simulations, we demonstrate that our approach has good true positive rates and well-calibrated false discovery rates. Applied to experimental data, our method identifies biologically relevant DSP genes while maintaining computational efficiency. Our framework has been implemented within the DESpace Bioconductor R package (from version 2.0.0).

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Cai, P., Robinson, M. D., Tiberi, S.. 2025-07-02. DESpace2: detection of differential spatial patterns in spatial omics data. https://doi.org/10.1101/2025.06.30.662268

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