Title
Simultaneous model discrimination and parameter estimation in dynamic models of cellular systems.
Abstract
Model development is a key task in systems biology, which typically starts from an initial model candidate and, involving an iterative cycle of hypotheses-driven model modifications, leads to new experimentation and subsequent model identification steps. The final product of this cycle is a satisfactory refined model of the biological phenomena under study. During such iterative model development, researchers frequently propose a set of model candidates from which the best alternative must be selected. Here we consider this problem of model selection and formulate it as a simultaneous model selection and parameter identification problem. More precisely, we consider a general mixed-integer nonlinear programming (MINLP) formulation for model selection and identification, with emphasis on dynamic models consisting of sets of either ODEs (ordinary differential equations) or DAEs (differential algebraic equations).We solved the MINLP formulation for model selection and identification using an algorithm based on Scatter Search (SS). We illustrate the capabilities and efficiency of the proposed strategy with a case study considering the KdpD/KdpE system regulating potassium homeostasis in Escherichia coli. The proposed approach resulted in a final model that presents a better fit to the in silico generated experimental data.The presented MINLP-based optimization approach for nested-model selection and identification is a powerful methodology for model development in systems biology. This strategy can be used to perform model selection and parameter estimation in one single step, thus greatly reducing the number of experiments and computations of traditional modeling approaches.
Year
DOI
Venue
2013
10.1186/1752-0509-7-76
BMC systems biology
Keywords
Field
DocType
systems biology,homeostasis,bioinformatics,potassium,algorithms,escherichia coli
Mathematical optimization,Iterative and incremental development,Ordinary differential equation,Global optimization,Computer science,Nonlinear programming,Model selection,Differential algebraic equation,Bioinformatics,System identification,Parameter identification problem
Journal
Volume
Issue
ISSN
7
1
1752-0509
Citations 
PageRank 
References 
11
0.60
21
Authors
4
Name
Order
Citations
PageRank
Maria Rodriguez-Fernandez116211.05
Markus Rehberg2110.94
Andreas Kremling3539.60
Julio R. Banga466550.71