Background: Gene co-expression networks (GCNs) are powerful tools that enable biologists to examine associations between genes during different biological processes. With the advancement of new technologies, such as single-cell RNA sequencing (scRNA-seq), there is a need for developing novel network methods appropriate for new types of data.Results: We present a novel sparse Bayesian factor model to explore the network structure associated with genes in scRNA-seq data. Latent factors impact the gene expression values for each cell and provide flexibility to account for common features of scRNA-seq: high proportions of zero values, increased cell-to-cell variability, and overdispersion due to abnormally large expression counts. From our model, we construct a GCN by analyzing the positive and negative associations of the factors that are shared between each pair of genes.Conclusions: Simulation studies demonstrate that our methodology has high power in identifying gene-gene associations while maintaining a nominal false discovery rate. In real data analyses, our model identifies more known and predicted protein-protein interactions than other competing network models.

Cellular communication through biochemical signaling is fundamental to every biological activity. Investigating cell signaling diffusions across cell types can further help understand biological mechanisms. In recent years, this has become an important research topic as single-cell sequencing technologies have matured. However, cell signaling activities are spatially constrained, and single-cell data cannot provide spatial information for each cell. This issue may cause a high false discovery rate, and using spatially resolved transcriptomics data is necessary. On the other hand, as far as we know, most existing methods focus on providing an ad hoc measurement to estimate intercellular communication instead of relying on a statistical model. It is undeniable that descriptive statistics are straightforward and accessible, but a suitable statistical model can provide more accurate and reliable inference. In this way, we propose a generalized linear regression model to infer cellular communications from spatially resolved transcriptomics data, especially spot-based data. Our BAyesian Tweedie modeling of COMmunications (BATCOM) method estimates the communication scores between cell types with the consideration of their corresponding distances. Due to the properties of the regression model, BATCOM naturally provides the direction of the communication between cell types and the interaction of ligands and receptors that other approaches cannot offer. We conduct simulation studies to assess the performance under different scenarios. We also employ BATCOM in a real-data application and compare it with other existing algorithms. In summary, our innovative model can fill gaps in the inference of cell–cell communication and provide a robust and straightforward result.