ArticleCommunications biology2019
Stochastic modelling reveals mechanisms of metabolic heterogeneity.
Article in Communications biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Multi-Scale Hybrid Modeling to Predict Cell Culture Process With Metabolic Phase Transitions.Biotechnology and bioengineering · 2026Article
- Metabolic inequality in microbial communities.bioRxiv : the preprint server for biology · 2026Article
- Bayesian inference captures metabolite-bacteria interactions in a microbial community.ISME communications · 2026Article
- Exploring single-cell biosynthetic noise and dynamics for enhanced betaxanthin production in Escherichia coli.Nature communications · 2025Article
- Recent Developments in Single-Cell Metabolomics by Mass Spectrometry─A Perspective.Journal of proteome research · 2025Review
- Dormancy in the origin, evolution and persistence of life on Earth.Proceedings. Biological sciences · 2025Review
- Unveiling inter-embryo variability in spindle length over time: Towards quantitative phenotype analysis.PLoS computational biology · 2024Article
- Futile lipid cycling: from biochemistry to physiology.Nature metabolism · 2024Review
- Bayesian Optimization for Design of Multiscale Biological Circuits.ACS synthetic biology · 2023Article
- Machine Learning and Hybrid Methods for Metabolic Pathway Modeling.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Applications of artificial intelligence multiomics in precision oncology.Journal of cancer research and clinical oncology · 2023Review
- Intercellular interaction mechanisms promote diversity in intracellular ATP concentration in Escherichia coli populations.Scientific reports · 2022Article
- Stabilization of antithetic control via molecular buffering.Journal of the Royal Society, Interface · 2022Article
- Toward modeling metabolic state from single-cell transcriptomics.Molecular metabolism · 2022Review
- Simulating single-cell metabolism using a stochastic flux-balance analysis algorithm.Biophysical journal · 2021Article
- Cell Growth Model with Stochastic Gene Expression Helps Understand the Growth Advantage of Metabolic Exchange and Auxotrophy.mSystems · 2021Article
- Understanding breast cancer heterogeneity through non-genetic heterogeneity.Breast cancer (Tokyo, Japan) · 2021Review
- Pareto optimality between growth-rate and lag-time couples metabolic noise to phenotypic heterogeneity in Escherichia coli.Nature communications · 2021Article
- Microbial metabolic noise.WIREs mechanisms of disease · 2021Review
- Coordination of gene expression noise with cell size: analytical results for agent-based models of growing cell populations.Journal of the Royal Society, Interface · 2021Article
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Authors and funding
4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Phenotypic variation is a hallmark of cellular physiology. Metabolic heterogeneity, in particular, underpins single-cell phenomena such as microbial drug tolerance and growth variability. Much research has focussed on transcriptomic and proteomic heterogeneity, yet it remains unclear if such variation permeates to the metabolic state of a cell. Here we propose a stochastic model to show that complex forms of metabolic heterogeneity emerge from fluctuations in enzyme expression and catalysis. The analysis predicts clonal populations to split into two or more metabolically distinct subpopulations. We reveal mechanisms not seen in deterministic models, in which enzymes with unimodal expression distributions lead to metabolites with a bimodal or multimodal distribution across the population. Based on published data, the results suggest that metabolite heterogeneity may be more pervasive than previously thought. Our work casts light on links between gene expression and metabolism, and provides a theory to probe the sources of metabolite heterogeneity.
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