Overview of glmSMA. GlmSMA is designed to estimate the linear relationship between spatial gene expression at specific locations and cellular expression of marker genes, incorporating both L1 and generalized L2 norms for optimal mapping precision. The L1 norm encourages sparsity, ensuring that most single cells are assigned to a small, defined patch within the reference atlas. The generalized L2 norm, meanwhile, promotes smoothness in cell distribution by leveraging anatomical structures and spatial coordinates. This refined mapping can then be used to enhance original spatial patterns and facilitate detailed studies of cell-to-cell communication within the spatial context.

glmSMA reconstruct spatial organization in the mouse cortex.

a, Comprehensive Mapping of Cells in the Mouse Brain Cortex: Mapping of 4,785 cells, representing 13 distinct cell types, within the mouse brain cortex, visualizing the spatial organization of these cellular populations. b, KL-Divergence Analysis Across Methods: A comparison of Kullback-Leibler (KL) divergence values between predicted cell type distributions and ground truth distributions across three methods. Results show that glmSMA achieves superior prediction accuracy for most cell types, aligning closely with actual distribution patterns.

c, Comparison of predicted and ground truth cell distributions in specific cell types.

Cell enrichment in the intestinal villus and human PDAC-sample lacking spatially informative genes. a, Violin plots illustrate the pairwise expression differences between spots. Expression differences increase as the physical distance between spots grows. b, Marker gene expression levels across different locations. Adjacent spots can exhibit significantly different expression levels. c, The enrichment of cell types in different anatomical structures. The predicted cell enrichment closely aligned with the ground truth for most cell types. d, The number of cells assigned to each region in intestinal villus.

Reconstruction of drosophila embryo. a, Overall 1,297 cell assignment in drosophila embryo. Multiple cells can be assigned to same locations. b, Individual cell assignment. Each cell will be assign to a small patch. c, Comparison of glmSMA, perler and novosparc results for reconstruction of marker genes in a drosophila embryo.

Reconstruction of mouse cerebellum. a, Simulation results of glmSMA for cell assignment in the mouse cerebellum. b, Comparsion of glmSMA, DistMap, novosparc and perler results for Granule cell and Purkinje cell assignments in the mouse cerebellum. c, Comparsion of glmSMA, DistMap denovosparc and novosparc results for Granule cell assignment in the specific anatomical region. d, Reconstruction of Car8 gene using glmSMA with the reconstructed pattern consistent with the ground truth.