MetDFBA: Incorporating time-resolved metabolomics measurements into dynamic flux balance analysis
Willemsen AM, Hendrickx DM, Hoefsloot HCJ, Hendriks MMWB, Teusink B, Smilde AK, Van Kampen AHC, Wahl SA (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 11
Pages Range: 137-145
Journal Issue: 1
DOI: 10.1039/c4mb00510d
Abstract
Understanding cellular adaptation to environmental changes is one of the major challenges in systems biology. To understand how cellular systems react towards perturbations of their steady state, the metabolic dynamics have to be described. Dynamic properties can be studied with kinetic models but development of such models is hampered by limited in vivo information, especially kinetic parameters. Therefore, there is a need for mathematical frameworks that use a minimal amount of kinetic information. One of these frameworks is dynamic flux balance analysis (DFBA), a method based on the assumption that cellular metabolism has evolved towards optimal changes to perturbations. However, DFBA has some limitations. It is less suitable for larger systems because of the high number of parameters to estimate and the computational complexity. In this paper, we propose MetDFBA, a modification of DFBA, that incorporates measured time series of both intracellular and extracellular metabolite concentrations, in order to reduce both the number of parameters to estimate and the computational complexity. MetDFBA can be used to estimate dynamic flux profiles and, in addition, test hypotheses about metabolic regulation. In a first case study, we demonstrate the validity of our method by comparing our results to flux estimations based on dynamic 13C MFA measurements, which we considered as experimental reference. For these estimations time-resolved metabolomics data from a feast-famine experiment with Penicillium chrysogenum was used. In a second case study, we used time-resolved metabolomics data from glucose pulse experiments during aerobic growth of Saccharomyces cerevisiae to test various metabolic objectives. This journal is
Authors with CRIS profile
Involved external institutions
Delft University of Technology (TU Delft)
Netherlands (NL)
University of Amsterdam
Netherlands (NL)
Vrije Universiteit Amsterdam (VU) / University Amsterdam
Netherlands (NL)
DSM ChemTech R&D B.V.
Netherlands (NL)
Netherlands (NL)
University of Amsterdam
Netherlands (NL)
Vrije Universiteit Amsterdam (VU) / University Amsterdam
Netherlands (NL)
DSM ChemTech R&D B.V.
Netherlands (NL)
How to cite
APA:
Willemsen, A.M., Hendrickx, D.M., Hoefsloot, H.C.J., Hendriks, M.M.W.B., Teusink, B., Smilde, A.K.,... Wahl, S.A. (2015). MetDFBA: Incorporating time-resolved metabolomics measurements into dynamic flux balance analysis. Molecular BioSystems, 11(1), 137-145. https://dx.doi.org/10.1039/c4mb00510d
MLA:
Willemsen, A. Marcel, et al. "MetDFBA: Incorporating time-resolved metabolomics measurements into dynamic flux balance analysis." Molecular BioSystems 11.1 (2015): 137-145.
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