SpaceX: Gene Co-expression Network Estimation for Spatial Transcriptomics

Abstract

MotivationThe analysis of spatially-resolved transcriptome enables the understanding of the spatial interactions between the cellular environment and transcriptional regulation. In particular, the characterization of the gene-gene co-expression at distinct spatial locations or cell types in the tissue enables delineation of spatial co-regulatory patterns as opposed to standard differential single gene analyses. To enhance the ability and potential of spatial transcriptomics technologies to drive biological discovery, we develop a statistical framework to detect gene co-expression patterns in a spatially structured tissue consisting of different clusters in the form of cell classes or tissue domains. ResultsWe develop SpaceX (spatially dependent gene co-expression network), a Bayesian methodology to identify both shared and cluster-specific co-expression network across genes. SpaceX uses an over-dispersed spatial Poisson model coupled with a high-dimensional factor model which is based on a dimension reduction technique for computational efficiency. We show via simulations, accuracy gains in co-expression network estimation and structure by accounting for (increasing) spatial correlation and appropriate noise distributions. In-depth analysis of two spatial transcriptomics datasets in mouse hypothalamus and human breast cancer using SpaceX, detected multiple hub genes which are related to cognitive abilities for the hypothalamus data and multiple cancer genes (e.g. collagen family) from the tumor region for the breast cancer data. Availability and implementationThe SpaceX R-package is available at github.com/bayesrx/SpaceX. Contactxzhousph@umich.edu, veerab@umich.edu Supplementary informationSupplementary data are available at bookdown.org/satwik91/SpaceX_supplementary/.