A network regularized linear model to infer spatial expression pattern for single cell

Abstract Spatial transcriptomics, situated at the intersection of genomics and spatial biology, offers profound insights into the spatial organization of gene expression within tissues. However, its potential has been constrained by either limited resolution or throughput. While single-cell RNA-seq allows for in-depth profiling of cellular gene expression, the crucial spatial information is often sacrificed during sample collection. In a groundbreaking fusion of these two techniques, our research introduces the glmSMA computational algorithm. This innovative approach aims to predict cell locations by integrating scRNA-seq data with spatial-omics reference atlases. The essence of glmSMA lies in formulating cell mapping as a convex problem, strategically minimizing differences between cellular expression profiles and location expression profiles through L1 and Generalized L2 regularization. Our algorithm has undergone rigorous testing across diverse tissues, including mouse brain, drosophila embryo, and human PDAC samples. The compelling results validate glmSMA’s efficacy, demonstrating its capability to faithfully recapitulate spatial gene expression and anatomical structures. This marks a significant stride forward in overcoming the limitations of existing spatial transcriptomic techniques.