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Open Access Highly Accessed Research article

Parameter optimization in S-system models

Marco Vilela15*, I-Chun Chou2, Susana Vinga3, Ana Tereza R Vasconcelos4, Eberhard O Voit2 and Jonas S Almeida15

Author Affiliations

1 Dept. Bioinformatics and Computational Biology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA

2 Dept. Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA

3 Instituto de Engenharia de Sistemas e Computadores: Investigação e Desenvolvimento (INESC-ID), R. Alves Redol 9, 1000-029 Lisboa, Portugal

4 Dept. Computatinal and Applied Mathematics, Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro, Brazil

5 Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Rua da Quinta Grande 6, Apartado 127, 2780-156 Oeiras, Portugal

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BMC Systems Biology 2008, 2:35  doi:10.1186/1752-0509-2-35

Published: 16 April 2008

Abstract

Background

The inverse problem of identifying the topology of biological networks from their time series responses is a cornerstone challenge in systems biology. We tackle this challenge here through the parameterization of S-system models. It was previously shown that parameter identification can be performed as an optimization based on the decoupling of the differential S-system equations, which results in a set of algebraic equations.

Results

A novel parameterization solution is proposed for the identification of S-system models from time series when no information about the network topology is known. The method is based on eigenvector optimization of a matrix formed from multiple regression equations of the linearized decoupled S-system. Furthermore, the algorithm is extended to the optimization of network topologies with constraints on metabolites and fluxes. These constraints rejoin the system in cases where it had been fragmented by decoupling. We demonstrate with synthetic time series why the algorithm can be expected to converge in most cases.

Conclusion

A procedure was developed that facilitates automated reverse engineering tasks for biological networks using S-systems. The proposed method of eigenvector optimization constitutes an advancement over S-system parameter identification from time series using a recent method called Alternating Regression. The proposed method overcomes convergence issues encountered in alternate regression by identifying nonlinear constraints that restrict the search space to computationally feasible solutions. Because the parameter identification is still performed for each metabolite separately, the modularity and linear time characteristics of the alternating regression method are preserved. Simulation studies illustrate how the proposed algorithm identifies the correct network topology out of a collection of models which all fit the dynamical time series essentially equally well.