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Math Biosci. 2013 Dec;246(2):315-25. doi: 10.1016/j.mbs.2013.01.008. Epub 2013 Feb 5.

Characterizability of metabolic pathway systems from time series data.

Author information

  • 1The Wallace H. Coulter, Department of Biomedical Engineering at Georgia Tech. and Emory University, 313 Ferst Drive, Suite 4103, Atlanta, GA 30332-0535, United States. Electronic address: eberhard.voit@bme.gatech.edu.

Abstract

Over the past decade, the biomathematical community has devoted substantial effort to the complicated challenge of estimating parameter values for biological systems models. An even more difficult issue is the characterization of functional forms for the processes that govern these systems. Most parameter estimation approaches tacitly assume that these forms are known or can be assumed with some validity. However, this assumption is not always true. The recently proposed method of Dynamic Flux Estimation (DFE) addresses this problem in a genuinely novel fashion for metabolic pathway systems. Specifically, DFE allows the characterization of fluxes within such systems through an analysis of metabolic time series data. Its main drawback is the fact that DFE can only directly be applied if the pathway system contains as many metabolites as unknown fluxes. This situation is unfortunately rare. To overcome this roadblock, earlier work in this field had proposed strategies for augmenting the set of unknown fluxes with independent kinetic information, which however is not always available. Employing Moore-Penrose pseudo-inverse methods of linear algebra, the present article discusses an approach for characterizing fluxes from metabolic time series data that is applicable even if the pathway system is underdetermined and contains more fluxes than metabolites. Intriguingly, this approach is independent of a specific modeling framework and unaffected by noise in the experimental time series data. The results reveal whether any fluxes may be characterized and, if so, which subset is characterizable. They also help with the identification of fluxes that, if they could be determined independently, would allow the application of DFE.

Copyright © 2013 Elsevier Inc. All rights reserved.

KEYWORDS:

Characterizability; Dynamic flux estimation; Identifiability; Metabolic pathway; Moore–Penrose inverse; Parameter estimation

PMID:
23391489
[PubMed - indexed for MEDLINE]
PMCID:
PMC3709000
Free PMC Article
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