Motivation The 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. Results We 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 implementation The SpaceX R-package is available at github.com/bayesrx/SpaceX. Supplementary information Supplementary data are available at bookdown.org/satwik91/SpaceX_supplementary/.

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Motivation: The 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. Results: We 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.

Analysis of structural and functional connectivity (FC) of human brains is of pivotal importance for diagnosis of cognitive ability. The Human Connectome Project (HCP) provides an excellent source of neural data across different regions of interest (ROIs) of the living human brain. Individual specific data were available from an existing analysis (Dai et al., 2017) in the form of time varying covariance matrices representing the brain activity as the subjects perform a specific task. As a preliminary objective of studying the heterogeneity of brain connectomics across the population, we develop a probabilistic model for a sample of covariance matrices using a scaled Wishart distribution. We stress here that our data units are available in the form of covariance matrices, and we use the Wishart distribution to create our likelihood function rather than its more common usage as a prior on covariance matrices. Based on empirical explorations suggesting the data matrices to have low effective rank, we further model the center of the Wishart distribution using an orthogonal factor model type decomposition. We encourage shrinkage towards a low rank structure through a novel shrinkage prior and discuss strategies to sample from the posterior distribution using a combination of Gibbs and slice sampling. We extend our modeling framework to a dynamic setting to detect change points. The efficacy of the approach is explored in various 1

Analysis of structural and functional connectivity (FC) of human brains is of pivotal importance for diagnosis of cognitive ability. The Human Connectome Project (HCP) provides an excellent source of neural data across different regions of interest (ROIs) of the living human brain. Individual specific data were available in the form of time varying covariance matrices representing the brain activity as the subjects perform a specific task. As a preliminary objective of studying the heterogeneity of brain connectomics across the population, we develop a probabilistic model for a sample of covariance matrices using a scaled Wishart distribution. We stress here that our data units are available in the form of covariance matrices, and we use the Wishart distribution to create our likelihood function rather than its more common usage as a prior on covariance matrices. Based on empirical explorations suggesting the data matrices to have a low effective rank, we further model the center of the Wishart distribution using an orthogonal factor model type decomposition. We encourage shrinkage toward a low rank structure through a novel shrinkage prior and discuss strategies to sample from the posterior distribution using a combination of Gibbs and slice sampling. The efficacy of the approach is explored in various simulation settings and exemplified on several case studies including our motivating HCP data. We extend our modeling framework to a dynamic setting to detect change points.