Recovering Spatially-Varying Cell-Specific Gene Co-expression Networks for Single-Cell Spatial Expression Data.

Abstract

Recent advances in single-cell technologies enable spatial expression profiling at the cell level, making it possible to elucidate spatial changes of cell-specific genomic features. The gene co-expression network is an important feature that encodes the gene-gene marginal dependence structure and allows for the functional annotation of highly connected genes. In this paper, we design a simple and computationally efficient two-step algorithm to recover spatially-varying cell-specific gene co-expression networks for single-cell spatial expression data. The algorithm first estimates the gene expression covariance matrix for each cell type and then leverages the spatial locations of cells to construct cell-specific networks. The second step uses expression covariance matrices estimated in step one and label information from neighboring cells as an empirical prior to obtain thresholded Bayesian posterior estimates. After completing estimates for each cell, this algorithm can further predict or interpolate gene co-expression networks on tissue positions where cells are not captured. In the simulation study, the comparison against the traditional cell-type-specific network algorithms and the cell-specific network method but without incorporating spatial information highlights the advantages of the proposed algorithm in estimation accuracy. We also applied our algorithm to real-world datasets and found some meaningful biological results. The accompanied software is available on https://github.com/jingeyu/CSSN.