Computation of single-cell metabolite distributions using mixture models
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Published version
Author(s)
Tonn, Mona
Thomas, Philipp
Barahona, Mauricio
Oyarzun, Diego
Type
Journal Article
Abstract
Metabolic heterogeneity is widely recognized as the next challenge in our understanding of non-genetic variation. A growing body of evidence suggests that metabolic heterogeneity may result from the inherent stochasticity of intracellular events. However, metabolism has been traditionally viewed as a purely deterministic process, on the basis that highly abundant metabolites tend to filter out stochastic phenomena. Here we bridge this gap with a general method for prediction of metabolite distributions across single cells. By exploiting the separation of time scales between enzyme expression and enzyme kinetics, our method produces estimates for metabolite distributions without the lengthy stochastic simulations that would be typically required for large metabolic models. The metabolite distributions take the form of Gaussian mixture models that are directly computable from single-cell expression data and standard deterministic models for metabolic pathways. The proposed mixture models provide a systematic method to predict the impact of biochemical parameters on metabolite distributions. Our method lays the groundwork for identifying the molecular processes that shape metabolic heterogeneity and its functional implications in disease.
Date Issued
2020-12-22
Date Acceptance
2020-11-26
Citation
Frontiers in Cell and Developmental Biology, 2020, 8, pp.1-11
ISSN
2296-634X
Publisher
Frontiers Media
Start Page
1
End Page
11
Journal / Book Title
Frontiers in Cell and Developmental Biology
Volume
8
Copyright Statement
© 2020 Tonn, Thomas, Barahona and Oyarzún. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Sponsor
Engineering & Physical Science Research Council (EPSRC)
Medical Research Council (MRC)
Human Frontier Science Program
Identifier
https://www.frontiersin.org/articles/10.3389/fcell.2020.614832/full
Grant Number
EP/N014529/1
MR/T018429/1
7922460 - RGY-0076/2015
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Developmental Biology
metabolic variability
stochastic gene expression
metabolic modeling
single-cell modeling
mixture model analysis
GENE-EXPRESSION
MASS-SPECTROMETRY
HETEROGENEITY
STOCHASTICITY
FLUCTUATIONS
VARIABILITY
PRINCIPLES
DYNAMICS
SYSTEMS
GROWTH
metabolic modeling
metabolic variability
mixture model analysis
single-cell modeling
stochastic gene expression
q-bio.MN
q-bio.MN
q-bio.BM
q-bio.QM
q-bio.SC
Publication Status
Published
Article Number
614832
Date Publish Online
2020-12-22