Deciphering the Spatial Modular Patterns of Tissues by Integrating Spatial and Single-Cell Transcriptomic Data

Single-cell RNA sequencing (scRNA-seq) provides a powerful tool to analyze the expression level of tissues at a cellular resolution. However, it could not capture the spatial organization of cells in a tissue. The spatially resolved transcriptomics technologies (ST) have been developed to address this issue. However, the emerging STs are still inefficient at single-cell resolution and/or fail to capture the sufficient reads. To this end, we adopted a partial least squares-based method (spatial modular patterns [SpaMOD]) to simultaneously integrate the two data modalities, as well as the networks related to cells and spots, to identify the cell-spot comodules for deciphering the SpaMOD of tissues. We applied SpaMOD to three paired scRNA-seq and ST datasets, derived from the mouse brain, granuloma, and pancreatic ductal adenocarcinoma, respectively. The identified cell-spot comodules provide detailed biological insights into the spatial relationships between cell populations and their spatial locations in the tissue.