Coordination of gene expression noise with cell size: analytical results for agent-based models of growing cell populations
File(s)
Accepted version
Author(s)
Thomas, Philipp
Shahrezaei, Vahid
Type
Journal Article
Abstract
The chemical master equation and the Gillespie algorithm are widely used to model the reaction kinetics inside living cells. It is thereby assumed that cell growth and division can be modelled through effective dilution reactions and extrinsic noise sources. We here re-examine these paradigms through developing an analytical agent-based framework of growing and dividing cells accompanied by an exact simulation algorithm, which allows us to quantify the dynamics of virtually any intracellular reaction network affected by stochastic cell size control and division noise. We find that the solution of the chemical master equation—including static extrinsic noise—exactly agrees with the agent-based formulation when the network under study exhibits stochastic concentration homeostasis, a novel condition that generalizes concentration homeostasis in deterministic systems to higher order moments and distributions. We illustrate stochastic concentration homeostasis for a range of common gene expression networks. When this condition is not met, we demonstrate by extending the linear noise approximation to agent-based models that the dependence of gene expression noise on cell size can qualitatively deviate from the chemical master equation. Surprisingly, the total noise of the agent-based approach can still be well approximated by extrinsic noise models.
Date Issued
2021-05-26
Date Acceptance
2021-05-04
Citation
Journal of the Royal Society Interface, 2021, 18 (178), pp.1-16
ISSN
1742-5662
Publisher
The Royal Society
Start Page
1
End Page
16
Journal / Book Title
Journal of the Royal Society Interface
Volume
18
Issue
178
Copyright Statement
© 2021 The Author(s)
Sponsor
Medical Research Council (MRC)
Engineering & Physical Science Research Council (EPSRC)
Identifier
https://royalsocietypublishing.org/doi/10.1098/rsif.2021.0274
Grant Number
MR/T018429/1
EP/N014529/1
Subjects
agent-based modelling
chemical master equation
single-cell analysis
stochastic gene expression
General Science & Technology
Publication Status
Published
Date Publish Online
2021-05-26