Transcriptional noise adjusted for expression levels reveals genes with high transcriptional noise that are highly expressed, functionally related, and co-regulated in yeast.

Understanding the relationship between variability in single-cell and non-single-cell gene expression studies will aid in understanding the role of and mechanisms that lead to variability in biological systems. Studies on the variation of gene expression levels in yeast normally focus on single cells and use the coefficient of variance (CV) as a measure of noise. The CV is typically negatively correlated with gene expression levels, so most of the studies using yeast find that genes with high transcriptional noise are lowly expressed. We find adjusting noise for expression levels using linear/natural log polynomial, and local fits and analyzing many non-single-cell RNA-seq sets identifies genes with high median transcriptional noise that are different than those that have high median CVs. Interestingly, these genes are heavily regulated by transcription factors that are related to variability and stochastic processes based on single-cell studies, including Msn2p, Msn4p, Hsf1p, and Crz1p but are not associated with genes with high median CVs based on non-single-cell gene expression data. In addition, adjusting noise for expression levels in a single-cell RNA-seq data set adds value by finding genes that have noisy gene expression levels and their associated transcription factors that are not found to be associated with genes with high CVs in the single-cell expression data or a comparable non-single-cell gene expression data. Lastly, S. cerevisiae genes with noisy expression tend to have orthologs with noisy gene expression in C. albicans, indicating transcriptional noise is evolutionarily conserved.