Identification of regulatory structure and kinetic parameters of biochemical networks via mixed-integer dynamic optimization

BMC Systems Biology

Laureano Jiménez²  Albert Sorribas²  Rui Alves²  Antoni Miró¹  Gonzalo Guillén-Gosálbez¹ 

[1] Departament d’Enginyeria Química, Universitat Rovira i Virgili, Av.Països Catalans 26, 43007 Tarragona, Spain;Departament de Ciències Mèdiques Bàsiques, Institut de Recerca Biomèdica de Lleida (IRBLLEIDA), Universitat de Lleida, Avinguda Alcalde Rovira Roure 80, 25198 Lleida, Spain

关键词: Biochemical networks;    Dynamic optimization;    Orthogonal collocation;    Akaike criterion;    Structure identification;    Parameter estimation;   

Others  :  1141966
DOI  :  10.1186/1752-0509-7-113

 received in 2013-03-26, accepted in 2013-10-14,  发布年份 2013

【 摘 要 】

Background

Recovering the network topology and associated kinetic parameter values from time-series data are central topics in systems biology. Nevertheless, methods that simultaneously do both are few and lack generality.

Results

Here, we present a rigorous approach for simultaneously estimating the parameters and regulatory topology of biochemical networks from time-series data. The parameter estimation task is formulated as a mixed-integer dynamic optimization problem with: (i) binary variables, used to model the existence of regulatory interactions and kinetic effects of metabolites in the network processes; and (ii) continuous variables, denoting metabolites concentrations and kinetic parameters values. The approach simultaneously optimizes the Akaike criterion, which captures the trade-off between complexity (measured by the number of parameters), and accuracy of the fitting. This simultaneous optimization mitigates a possible overfitting that could result from addition of spurious regulatory interactions.

Conclusion

The capabilities of our approach were tested in one benchmark problem. Our algorithm is able to identify a set of plausible network topologies with their associated parameters.

【 授权许可】

   
2013 Guillén-Gosálbez et al.; licensee BioMed Central Ltd.

【 图 表 】

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