NDLI: Modular Parameter Identification of Biomolecular Networks

Content Provider	Society for Industrial and Applied Mathematics (SIAM)
Author	Stelling, Jörg Lang, Moritz
Copyright Year	2016
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.
Starting Page	B988
Ending Page	B1008
Page Count	21
File Format	PDF
ISSN	10648275
DOI	10.1137/15M103306X
e-ISSN	10957197
Issue Number	6
Volume Number	38
Language	English
Publisher	Society for Industrial and Applied Mathematics
Publisher Date	2016-11-15
Access Restriction	Subscribed
Subject Keyword	systems biology Inverse problems modularization Nonlinear programming parameter identification Systems biology, networks
Content Type	Text
Resource Type	Article
Subject	Applied Mathematics Computational Mathematics

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