Modular Parameter Identification of Biomolecular Networks

Lang, Moritz and Stelling, Jörg (2016) Modular Parameter Identification of Biomolecular Networks. SIAM Journal on Scientific Computing, 38 (6). B988-B1008. ISSN 1095-7197

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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.

Item Type: Article
DOI: 10.1137/15M103306X
Subjects: 000 Computer science, knowledge & general works > 000 Computer science, knowledge & systems > 003 Systems
500 Science > 510 Mathematics > 518 Numerical analysis
500 Science > 570 Life sciences; biology
600 Technology > 620 Engineering > 621 Applied physics
Research Group: Guet Group
Tkacik Group
Depositing User: Moritz Lang
Date Deposited: 20 Apr 2017 07:24
Last Modified: 15 Jul 2019 14:42

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