This is my undergraduate work at Dr. Zemin Zhang’s Lab at Peking Unviversity.
It starts with an interesting question: Can we infer the spatial information from scRNA-seq that is usually lost during tissue dissociation? We made a simple but reasonable assumption that spatially-close cells should have high ligand-receptor interactions. Based on that we developed CSOmap, a computational tool to infer cellular interaction de novo from scRNA-seq. We show that CSOmap can successfully recapitulate the spatial organization of multiple organs of human and mouse including tumor microenvironments for multiple cancers in pseudo-space, and reveal molecular determinants of cellular interactions. Further, CSOmap readily simulates perturbation of genes or cell types to gain novel biological insights, especially into how immune cells interact in the tumor microenvironment. CSOmap can be a widely applicable tool to interrogate cellular organizations based on scRNA-seq data for various tissues in diverse systems.
Demonstration of the model. a) CSOmap takes the gene-by-cell expression matrix generated by scRNA-seq and the known ligand-receptor network as inputs, upon which a cell-by-cell affinity matrix is estimated. b) The inherently high-dimensional cell-by-cell affinity matrix is embedded into a three-dimensional space via resolving cell competitions. c) Density can be estimated for individual cells based on their three-dimensional coordinates obtained from b, which allows the identification of spatially-defined cell clusters. d) Given the cell cluster labels, the number of connections among cell clusters and their statistical significance can be summarized and evaluated by CSOmap. e) For a pair of cell clusters, the contributions of each ligand-receptor pair to their interactions can be calculated. f CSOmap allows in silico interference of the original dataset including gene knockdown/overexpression and cell depletion/adoptive transfer to examine the corresponding effects on cellular spatial organizations.
It is a cool project, I really appreciate the mentorship from Dr. Xianwen Ren and Dr. Zemin Zhang. It is my first real experience in scientific research that I will never forget.
For details, please check our manuscript and GitHub repository.