Model reduction and a priori kinetic parameter identifiability analysis using metabolome time series for metabolic reaction networks with linlog kinetics

Metabolic Engineering
I Emrah NikerelJoseph J Heijnen

Abstract

In this work, we present a time-scale analysis based model reduction and parameter identifiability analysis method for metabolic reaction networks. The method uses the information obtained from short term chemostat perturbation experiments. We approximate the time constant of each metabolite pool by their turn-over time and classify the pools accordingly into two groups: fast and slow pools. We performed a priori model reduction, neglecting the dynamic term of the fast pools. By making use of the linlog approximative kinetics, we obtained a general explicit solution for the fast pools in terms of the slow pools by elaborating the degenerate algebraic system resulting from model reduction. The obtained relations yielded also analytical relations between a subset of kinetic parameters. These relations also allow to realize an analytical model reduction using lumped reaction kinetics. After solving these theoretical identifiability problems and performing model reduction, we carried out a Monte Carlo approach to study the practical identifiability problems. We illustrated the methodology on model reduction and theoretical/practical identifiability analysis on an example system representing the glycolysis in Saccharomyces cerevisia...Continue Reading

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Citations

Jun 3, 2014·BMC Systems Biology·Shodhan RaoBayu Jayawardhana
Dec 12, 2012·Journal of Mathematical Biology·Sara BerthoumieuxEugenio Cinquemani
Aug 10, 2010·BMC Bioinformatics·Suresh Kumar Poovathingal, Rudiyanto Gunawan
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Jun 21, 2011·Bioinformatics·Sara BerthoumieuxEugenio Cinquemani
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Mar 10, 2019·Current Opinion in Biotechnology·Jonathan StrutzKeith Tyo
Feb 6, 2020·Mathematical Biosciences·Hussein KansoValentina Baldazzi

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