Modular parameter identification of biomolecular networks Journal Article

Author(s): Lang, Moritz; Stelling, Jörg
Article Title: Modular parameter identification of biomolecular networks
Affiliation IST Austria
Abstract: The increasing complexity of dynamic models in systems and synthetic biology poses computational challenges especially for the identification of model parameters. While modularization of the corresponding optimization problems could help reduce the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit a simple decomposition of most biomolecular networks into subnetworks, or modules. Drawing on ideas from network modularization and multiple-shooting optimization, we present here a modular parameter identification approach that explicitly allows for such interdependencies. Interfaces between our modules are given by the experimentally measured molecular species. This definition allows deriving good (initial) estimates for the inter-module communication directly from the experimental data. Given these estimates, the states and parameter sensitivities of different modules can be integrated independently. To achieve consistency between modules, we iteratively adjust the estimates for inter-module communication while optimizing the parameters. After convergence to an optimal parameter set---but not during earlier iterations---the intermodule communication as well as the individual modules' state dynamics agree with the dynamics of the nonmodularized network. Our modular parameter identification approach allows for easy parallelization; it can reduce the computational complexity for larger networks and decrease the probability to converge to suboptimal local minima. We demonstrate the algorithm's performance in parameter estimation for two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling pathway.
Keywords: systems biology; Modularization; Parameter identification
Journal Title: SIAM Journal on Scientific Computing
Volume: 38
Issue 6
ISSN: 1095-7197
Publisher: Society for Industrial and Applied Mathematics  
Date Published: 2016-11-15
Start Page: B988
End Page: B1008
DOI: 10.1137/15M103306X
Open access: yes (repository)