Quantifying the phenotypic information in mRNA abundance.

Quantifying the dependency between mRNA abundance and downstream cellular phenotypes is a fundamental open problem in biology. Advances in multimodal single‐cell measurement technologies provide an opportunity to apply new computational frameworks to dissect the contribution of individual genes and gene combinations to a given phenotype. Using an information theory approach, we analyzed multimodal data of the expression of 83 genes in the Ca2+ signaling network and the dynamic Ca2+ response in the same cell. We found that the overall expression levels of these 83 genes explain approximately 60% of Ca2+ signal entropy. The average contribution of each single gene was 17%, revealing a large degree of redundancy between genes. Using different heuristics, we estimated the dependency between the size of a gene set and its information content, revealing that on average, a set of 53 genes contains 54% of the information about Ca2+ signaling. Our results provide the first direct quantification of information content about complex cellular phenotype that exists in mRNA abundance measurements. Synopsis: The dependency of cellular signaling dynamics variability on transcriptional state was estimated by applying information theory estimation to paired multimodal measurements of mRNA abundances and cellular cytosolic Ca2+ dynamics response to ATP.Overall expression levels of 83 genes related to Ca2+ signaling explain 60% of the observed variability in Ca2+ signaling dynamics.Most of the information provided by any single gene is redundant with other genes.54% of information about Ca2+ dynamics exists in the most informative set of 12 genes or a random set of 53 genes. [ABSTRACT FROM AUTHOR]