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

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...

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Detalles Bibliográficos
Autores: Guillén Gosálbez, Gonzalo, Miró, Antoni, Alves, Rui, Sorribas Tello, Albert, Jiménez Esteller, Laureano
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/48285
Acceso en línea:https://doi.org/10.1186/1752-0509-7-113
http://hdl.handle.net/10459.1/48285
Access Level:acceso abierto
Palabra clave:Parameter estimation
Structure identification
Akaike criterion
Descripción
Sumario: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 mixedinteger 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.