In silico method for modelling metabolism and gene product expression at genome scale
Open accessAbstract
Transcription and translation use raw materials and energy generated metabolically to create the macromolecular machinery responsible for all cellular functions, including metabolism. A biochemically accurate model of molecular biology and metabolism will facilitate comprehensive and quantitative computations of an organism's molecular constitution as a function of genetic and environmental parameters. Here we formulate a model of metabolism and macromolecular expression. Prototyping it using the simple microorganism Thermotoga maritima, we show our model accurately simulates variations in cellular composition and gene expression. Moreover, through in silico comparative transcriptomics, the model allows the discovery of new regulons and improving the genome and transcription unit annotations. Our method presents a framework for investigating molecular biology and cellular physiology in silico and may allow quantitative interpretation of multi-omics data sets in the context of an integrated biochemical description of an organism. To describe the biochemical composition of an organism multiple data sets must be combined and this information can then be used forin silico analysis. By combining metabolism and transcription data, Lerman et al. discovered new regulons and improved the gene annotation for the simple organism Thermotoga maritima.
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ME models have only been developed for Thermotoga maritima and Escherichia coli because they require detailed knowledge of all steps of protein synthesis that is not readily available for all organisms, particularly eukaryal cells.
“ME models have only been developed for Thermotoga maritima (Lerman et al, 2012) and E. coli (Orth et al, 2010) because they require detailed knowledge of all the steps of protein synthesis (protein maturation, protein folding, metal binding, etc.), which are not readily available for all organisms, and in particular for eukaryal cells.”
From Improving the phenotype predictions of a yeast genome‐scale metabolic model by incorporating enzymatic constraints (2017) · cites this paper as Lerman et al, 2012
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References 59 · Cited by 266
Research works printed but not linked: 1
- [14]Tiele I Dissertation: A Stoichiometric Model of Escherichia coli's Macromolecular Synthesis Machinery and its Integration with Metabolism ProQuest Ann Arbor, MI 2008
- Authors
- Lerman, J. A., Hyduke, D. R., Latif, H., Portnoy, V. A., Lewis, N. E., Orth, J. D., Schrimpe-Rutledge, A. C., Smith, R. D., Adkins, J. N., Zengler, K., & Palsson, B. O.
- Affiliations
- University of California San Diego (US)
- Pacific Northwest National Laboratory (US)
- ORCID
- Venue
- Nature Communications
- Published
- 2012-07-03
- Volume
- 3
- Issue
- 1
- Pages
- 929-929
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC3827721
- OpenAlex
- W2170298003
- Cited by
- 266
- References
- 59
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 14 · 2023: 18 · 2022: 10 · 2021: 39 · 2020: 16 · 2019: 19 · 2018: 18 · 2017: 21 · 2016: 23 · 2015: 22 · 2014: 23 · 2013: 20 · 2012: 4
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Energy (DE‐FG02‐, FG02-08ER64686)
- U.S. Department of Health and Human Services (Y1-AI-8401-01)
- National Institutes of Health (GM085764)
- National Institute of General Medical Sciences (GM 085764, P50GM085764, U01GM102098)
- National Institute of Allergy and Infectious Diseases (Y1-AI-8401, Y1-AI8401-01, Y01 AI008401)
- Pacific Northwest National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- genome-scale metabolic modeling, gene expression, macromolecular composition, transcription and translation, Thermotoga maritima, genome annotation, comparative transcriptomics, multi-omics integration, cell physiology, in silico modeling
- MeSH terms
- Computational Biology, Thermotoga maritima, Systems Biology, Transcriptome
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