Dimensionality reduction via path integration for computing mRNA distributions

DOI10.1007/S00285-021-01683-2MaRDI QIDQ2244906zbMATH OpenOpenAlexWikidataFDO

Authors Jaroslav Albert

Publication date 12 November 2021

Published in Journal of Mathematical Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/2006.08192

zbMATH Keywords

gene regulatory networksmaster equationprobability distributionspath integralpromotersingle-cell RNA data

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Systems biology, networks (92C42)

Abstract: Inherent stochasticity in gene expression leads to distributions of mRNA copy numbers in a population of identical cells. These distributions are determined primarily by the multitude of states of a gene promoter, each driving transcription at a different rate. In an era where single-cell mRNA copy number data are more and more available, there is an increasing need for fast computations of mRNA distributions. In this paper, we present a method for computing separate distributions for each species of mRNA molecules, i. e. mRNAs that have been either partially or fully processed post-transcription. The method involves the integration over all possible realizations of promoter states, which we cast into a set of linear ordinary differential equations of dimension $Mimes{n}_j$, where $M$ is the number of available promoter states and $n_j$ is the mRNA copy number of species $j$ up to which one wishes to compute the probability distribution. This approach is superior to solving the Master equation (ME) directly in two ways: a) the number of coupled differential equations in the ME approach is $MimesLambd{a}_{1}imesLambd{a}_{2}imes\mathrm{...}imesLambd{a}_L$, where $Lambd{a}_j$ is the cutoff for the probability of the $j^{extth}$ species of mRNA; and b) the ME must be solved up to the cutoffs $Lambd{a}_j$, which are {it ad hoc} and must be selected {it a priori}. In our approach, the equation for the probability to observe $n$ mRNAs of any species depends only on the the probability of observing $n-1$ mRNAs of that species, thus yielding a correct probability distribution up to an arbitrary $n$. To demonstrate the validity of our derivations, we compare our results with Gillespie simulations for ten randomly selected system parameters.

Recommendations

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Cites work

• A geometric analysis of fast-slow models for stochastic gene expression
• Adaptive simulation of hybrid stochastic and deterministic models for biochemical systems
• Efficient simulation of discrete stochastic reaction systems with a splitting method
• Exact and approximate distributions of protein and mRNA levels in the low-copy regime of gene expression
• Multiscale stochastic modelling of gene expression
• Path integral approach to generating functions for multistep post-transcription and post-translation processes and arbitrary initial conditions
• Probability distributions for multimeric systems
• Solving the chemical master equation for monomolecular reaction systems analytically
• Stochastic hybrid models of gene regulatory networks -- a PDE approach
• Time-dependent propagators for stochastic models of gene expression: an analytical method

Cited in

(1)

• Measurement of the number of molecules of a single mRNA species in a complex mRNA preparation

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