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The ETFL formulation allows multi-omics integration in thermodynamics-compliant metabolism and expression models

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  • Pierre Salvy

    (École Polytechnique Fédérale de Lausanne (EPFL))

  • Vassily Hatzimanikatis

    (École Polytechnique Fédérale de Lausanne (EPFL))

Abstract

Systems biology has long been interested in models capturing both metabolism and expression in a cell. We propose here an implementation of the metabolism and expression model formalism (ME-models), which we call ETFL, for Expression and Thermodynamics Flux models. ETFL is a hierarchical model formulation, from metabolism to RNA synthesis, that allows simulating thermodynamics-compliant intracellular fluxes as well as enzyme and mRNA concentration levels. ETFL formulates a mixed-integer linear problem (MILP) that enables both relative and absolute metabolite, protein, and mRNA concentration integration. ETFL is compatible with standard MILP solvers and does not require a non-linear solver, unlike the previous state of the art. It also accounts for growth-dependent parameters, such as relative protein or mRNA content. We present ETFL along with its validation using results obtained from a well-characterized E. coli model. We show that ETFL is able to reproduce proteome-limited growth. We also subject it to several analyses, including the prediction of feasible mRNA and enzyme concentrations and gene essentiality.

Suggested Citation

  • Pierre Salvy & Vassily Hatzimanikatis, 2020. "The ETFL formulation allows multi-omics integration in thermodynamics-compliant metabolism and expression models," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13818-7
    DOI: 10.1038/s41467-019-13818-7
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    Cited by:

    1. Asli Sahin & Daniel R. Weilandt & Vassily Hatzimanikatis, 2023. "Optimal enzyme utilization suggests that concentrations and thermodynamics determine binding mechanisms and enzyme saturations," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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