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Abstract
The rapidly developing spatial omics generated datasets with diverse scales and modalities. However, most existing methods focus on modeling dynamics of single cells while ignore microenvironments (MEs). Here we present SOTIP (Spatial Omics mulTIPle-task analysis), a versatile method incorporating MEs and their interrelationships into a unified graph. Based on this graph, spatial heterogeneity quantification, spatial domain identification, differential microenvironment analysis, and other downstream tasks can be performed. We validate each module’s accuracy, robustness, scalability and interpretability on various spatial omics datasets. In two independent mouse cerebral cortex spatial transcriptomics datasets, we reveal a gradient spatial heterogeneity pattern strongly correlated with the cortical depth. In human triple-negative breast cancer spatial proteomics datasets, we identify molecular polarizations and MEs associated with different patient survivals. Overall, by modeling biologically explainable MEs, SOTIP outperforms state-of-art methods and provides some perspectives for spatial omics data exploration and interpretation.
Methods that analyse heterogeneity and compare tissue microenvironments using spatial omics data are challenging to develop. Here, the authors present SOTIP, a method that can perform spatial heterogeneity, spatial domain, and differential microenvironment analyses across multiple spatial omics modalities.
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1 Fudan University, Institute of Science and Technology for Brain-Inspired Intelligence; MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence; MOE Frontiers Center for Brain Science, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Tencent AI Lab, Shenzhen, China (GRID:grid.471330.2) (ISNI:0000 0004 6359 9743); Tsinghua University, MOE Key Laboratory of Bioinformatics; Bioinformatics Division and Center for Synthetic & Systems Biology, BNRist; Department of Automation, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178)
2 Tsinghua University, MOE Key Laboratory of Bioinformatics; Bioinformatics Division and Center for Synthetic & Systems Biology, BNRist; Department of Automation, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178)
3 Tsinghua University, MOE Key Laboratory of Bioinformatics; Bioinformatics Division and Center for Synthetic & Systems Biology, School of Medicine, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178)
4 Tencent AI Lab, Shenzhen, China (GRID:grid.471330.2) (ISNI:0000 0004 6359 9743)
5 Tsinghua University, MOE Key Laboratory of Bioinformatics; Bioinformatics Division and Center for Synthetic & Systems Biology, BNRist; Department of Automation, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178); Tsinghua University, MOE Key Laboratory of Bioinformatics; Bioinformatics Division and Center for Synthetic & Systems Biology, School of Medicine, Beijing, China (GRID:grid.12527.33) (ISNI:0000 0001 0662 3178); The University of Texas, Department of Biological Sciences, Center for Systems Biology, Richardson, USA (GRID:grid.267323.1) (ISNI:0000 0001 2151 7939)