Addressing the mean-variance relationship in spatially resolved transcriptomics data with spoon.

An important task in the analysis of spatially resolved transcriptomics (SRT) data is to identify spatially variable genes (SVGs), or genes that vary in a 2D space. Current approaches rank SVGs based on either $ P $-values or an effect size, such as the proportion of spatial variance. However, previous work in the analysis of RNA-sequencing data identified a technical bias with log-transformation, violating the "mean-variance relationship" of gene counts, where highly expressed genes are more likely to have a higher variance in counts but lower variance after log-transformation. Here, we demonstrate the mean-variance relationship in SRT data. Furthermore, we propose spoon, a statistical framework using empirical Bayes techniques to remove this bias, leading to more accurate prioritization of SVGs. We demonstrate the performance of spoon in both simulated and real SRT data. A software implementation of our method is available at https://bioconductor.org/packages/spoon.