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Math Biosci. 2019 Nov 28:108291. doi: 10.1016/j.mbs.2019.108291. [Epub ahead of print]

Experimental design for parameter estimation in steady-state linear models of metabolic networks.

Author information

1
Department of Mathematics, University of Bergen, Bergen, Norway. Electronic address: havard.froysa@uib.no.
2
Department of Mathematics, University of Bergen, Bergen, Norway.

Abstract

Metabolic networks are typically large, containing many metabolites and reactions. Dynamical models that aim to simulate such networks will consist of a large number of ordinary differential equations, with many kinetic parameters that must be estimated from experimental data. We assume these data to be metabolomics measurements made under steady-state conditions for different input fluxes. Assuming linear kinetics, analytical criteria for parameter identifiability are provided. For normally distributed error terms, we also calculate the Fisher information matrix analytically to be used in the D-optimality criterion. A test network illustrates the developed tool chain for finding an optimal experimental design. The first stage is to verify global or pointwise parameter identifiability, the second stage to find optimal input fluxes, and finally remove redundant measurements.

KEYWORDS:

D-optimality; Experimental design; Fisher information; Metabolic networks; Parameter identifiability; Systems biology

PMID:
31786081
DOI:
10.1016/j.mbs.2019.108291

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