Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 18, Issue 8, Pages -Publisher
WILEY
DOI: 10.15252/msb.202211001
Keywords
cellular heterogeneity; gene expression; information theory; mutual information; signaling dynamics
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Funding
- NVIDIA Corporation
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Quantifying the dependency between mRNA abundance and downstream cellular phenotypes is a fundamental problem in biology. In this study, multimodal single-cell measurement data was used to analyze the expression of 83 genes in the Ca2+ signaling network and the dynamic Ca2+ response. It was found that the overall expression levels of these genes explain approximately 60% of Ca2+ signal entropy, with each single gene contributing an average of 17% and showing a large degree of redundancy. The study also 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.
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.
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