Method

Efficient integration of spatial omics data for joint domain detection, matching, and alignment with stMSA

    • 1School of Computer Science, Northwestern Polytechnical University, 710072 Shaanxi, China;
    • 2Key Laboratory of Big Data Storage and Management, Ministry of Industry and Information Technology, Northwestern Polytechnical University, 710072 Shaanxi, China;
    • 3School of Computer Science and Engineering, Xi'an University of Technology, 710048 Shaanxi, China;
    • 4Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore, 117543 Singapore, Singapore;
    • 5Center for Bioinformatics, School of Life Science and Technology, Harbin Institute of Technology, 150000 Heilongjiang, China;
    • 6School of Interdisciplinary Medicine and Engineering, Harbin Medical University, 150081 Heilongjiang, China
    • 7 These authors contributed equally to this work.
Published August 14, 2025. Vol 35 Issue 10, pp. 2285-2299. https://doi.org/10.1101/gr.280584.125
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Abstract

Spatial omics (SOs) are powerful methodologies that enable the study of genes, proteins, and other molecular features within the spatial context of tissue architecture. With the growing availability of SO data sets, researchers are eager to extract biological insights from larger data sets for a more comprehensive understanding. However, existing approaches focus on batch effect correction, often neglecting complex biological patterns in tissue slices, complicating feature integration and posing challenges when combining transcriptomics with other omics layers. Here, we introduce spatial multislice/omics analysis (stMSA), a deep graph contrastive learning model that incorporates graph auto-encoder techniques. stMSA is specifically designed to produce batch-corrected representations while retaining the distinct spatial patterns within each slice, considering both intra- and inter-batch relationships during integration. Extensive evaluations show that stMSA outperforms state-of-the-art methods in distinguishing tissue structures across diverse slices, even when faced with varying experimental protocols and sequencing technologies. Furthermore, stMSA effectively deciphers complex developmental trajectories by integrating spatial proteomics and transcriptomics data and excels in cross-slice matching and alignment for 3D tissue reconstruction.

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