Characterizing the non-monotonic behavior of mutual information along biochemical reaction cascades

TL;DR

This paper investigates how mutual information behaves along biochemical reaction cascades, revealing non-monotonic patterns due to noise and stochastic fluctuations, which impacts how cellular signaling is interpreted.

Contribution

It identifies conditions where mutual information increases along biochemical cascades, challenging the assumption of monotonic information transfer in cellular signaling.

Findings

Mutual information can increase along reaction cascades.

Noise propagation and stochastic fluctuations influence information measures.

Stationary distributions may not accurately reflect information transfer.

Abstract

Cells sense environmental signals and transmit information intracellularly through changes in the abundance of molecular components. Such molecular abundances can be measured in single cells and exhibit significant heterogeneity in clonal populations even in identical environments. Experimentally observed joint probability distributions can then be used to quantify the covariability and mutual information between molecular abundances along signaling cascades. However, because stationary state abundances along stochastic biochemical reaction cascades are not conditionally independent, their mutual information is not constrained by the data processing inequality. Here, we report the conditions under which the mutual information between stationary state abundances increases along a cascade of biochemical reactions. This non-monotonic behavior can be intuitively understood in terms of noise propagation and time-averaging stochastic fluctuations that are short-lived compared to an extrinsic signal. Our results re-emphasize that mutual information measurements of stationary state distributions of cellular components may be of limited utility for characterizing cellular signaling processes because they do not measure information transfer.