Stochastic models of gene transcription with upstream drives: Exact solution and sample path characterisation
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Published version
Author(s)
Dattani, J
Barahona, M
Type
Journal Article
Abstract
Gene transcription is a highly stochastic and dynamic process. As a result, the mRNA copy
number of a given gene is heterogeneous both between cells and across time. We present a framework
to model gene transcription in populations of cells with time-varying (stochastic or deterministic)
transcription and degradation rates. Such rates can be understood as upstream cellular drives
representing the effect of different aspects of the cellular environment. We show that the full solution
of the master equation contains two components: a model-specific, upstream effective drive, which
encapsulates the effect of cellular drives (e.g., entrainment, periodicity or promoter randomness),
and a downstream transcriptional Poissonian part, which is common to all models. Our analytical
framework treats cell-to-cell and dynamic variability consistently, unifying several approaches in the
literature. We apply the obtained solution to characterise different models of experimental relevance,
and to explain the influence on gene transcription of synchrony, stationarity, ergodicity, as well as
the effect of time-scales and other dynamic characteristics of drives. We also show how the solution
can be applied to the analysis of noise sources in single-cell data, and to reduce the computational
cost of stochastic simulations.
number of a given gene is heterogeneous both between cells and across time. We present a framework
to model gene transcription in populations of cells with time-varying (stochastic or deterministic)
transcription and degradation rates. Such rates can be understood as upstream cellular drives
representing the effect of different aspects of the cellular environment. We show that the full solution
of the master equation contains two components: a model-specific, upstream effective drive, which
encapsulates the effect of cellular drives (e.g., entrainment, periodicity or promoter randomness),
and a downstream transcriptional Poissonian part, which is common to all models. Our analytical
framework treats cell-to-cell and dynamic variability consistently, unifying several approaches in the
literature. We apply the obtained solution to characterise different models of experimental relevance,
and to explain the influence on gene transcription of synchrony, stationarity, ergodicity, as well as
the effect of time-scales and other dynamic characteristics of drives. We also show how the solution
can be applied to the analysis of noise sources in single-cell data, and to reduce the computational
cost of stochastic simulations.
Date Issued
2017-01-04
Date Acceptance
2016-11-29
Citation
Journal of the Royal Society Interface, 2017, 14 (126)
ISSN
1742-5689
Publisher
Royal Society, The
Journal / Book Title
Journal of the Royal Society Interface
Volume
14
Issue
126
Copyright Statement
© 2017 The Authors.
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Engineering & Physical Science Research Council (EPSRC)
Grant Number
EP/I017267/1
EP/N014529/1
Subjects
chemical master equation
gene expression
noise
non-stationarity
stochastic models
transcription
q-bio.QM
q-bio.MN
General Science & Technology
MD Multidisciplinary
Publication Status
Published
Article Number
20160833