DocumentCode :
1239956
Title :
Challenges in lin-log modelling of glycolysis in Lactococcus lactis
Author :
del Rosario, R.C.H. ; Mendoza, E. ; Voit, E.O.
Author_Institution :
Inst. of Math., Univ. of the Philippines, Quezon
Volume :
2
Issue :
3
fYear :
2008
fDate :
5/1/2008 12:00:00 AM
Firstpage :
136
Lastpage :
149
Abstract :
The performance of the lin-log method for modelling the glycolytic pathway in Lactococcus lactis using in vivo time-series data is investigated. The network structure of this pathway has been studied in previous reports and the authors concentrate here on the challenge of fitting the lin-log model parameters to experimental data. To calibrate the estimation methods, the performance of the lin-log method on a simpler model of a small gene regulatory system was first investigated, which has become a benchmark in the field. Two families of optimisation algorithms were employed. One computes the objective function by solving a system of ordinary differential equations (odes), whereas the other discretises the odes and incorporates them as nonlinear equality constraints in the optimisation problem. Gradient-based, simplex-based and stochastic search algorithms were used to solve the former, whereas only a gradient-based algorithm was used to solve the latter. Although the estimation methods succeeded in determining the parameter values for the small gene network model, they did not yield a satisfactory lin-log model for the glycolytic pathway. The main reasons are apparently that several system variables approach low, and ultimately zero concentrations, which are intrinsically problematic for lin-log models, and that this pathway does not offer a natural non-zero reference state.
Keywords :
biochemistry; biology computing; genetics; gradient methods; microorganisms; nonlinear differential equations; optimisation; physiological models; stochastic processes; time series; Loctococcus lactis; estimation methods; gene regulatory system; glycolysis; glycolytic pathway; gradient-based algorithm; in vivo time-series data; lin-log modelling; network structure; nonlinear equality constraints; optimisation algorithms; ordinary differential equations; simplex-based algorithms; stochastic search algorithms;
fLanguage :
English
Journal_Title :
Systems Biology, IET
Publisher :
iet
ISSN :
1751-8849
Type :
jour
DOI :
10.1049/iet-syb:20070030
Filename :
4537510
Link To Document :
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