--- _id: '1170' abstract: - lang: eng text: 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. author: - first_name: Moritz full_name: Lang, Moritz id: 29E0800A-F248-11E8-B48F-1D18A9856A87 last_name: Lang - first_name: Jörg full_name: Stelling, Jörg last_name: Stelling citation: ama: Lang M, Stelling J. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 2016;38(6):B988-B1008. doi:10.1137/15M103306X apa: Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics . https://doi.org/10.1137/15M103306X chicago: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics , 2016. https://doi.org/10.1137/15M103306X. ieee: M. Lang and J. Stelling, “Modular parameter identification of biomolecular networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society for Industrial and Applied Mathematics , pp. B988–B1008, 2016. ista: Lang M, Stelling J. 2016. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008. mla: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society for Industrial and Applied Mathematics , 2016, pp. B988–1008, doi:10.1137/15M103306X. short: M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008. date_created: 2018-12-11T11:50:31Z date_published: 2016-11-15T00:00:00Z date_updated: 2021-01-12T06:48:49Z day: '15' ddc: - '003' - '518' - '570' - '621' department: - _id: CaGu - _id: GaTk doi: 10.1137/15M103306X file: - access_level: local checksum: 781bc3ffd30b2dd65b7727c5a285fc78 content_type: application/pdf creator: system date_created: 2018-12-12T10:14:41Z date_updated: 2020-07-14T12:44:37Z file_id: '5095' file_name: IST-2017-811-v1+1_modular_parameter_identification.pdf file_size: 871964 relation: main_file file_date_updated: 2020-07-14T12:44:37Z has_accepted_license: '1' intvolume: ' 38' issue: '6' language: - iso: eng month: '11' oa_version: Submitted Version page: B988 - B1008 publication: SIAM Journal on Scientific Computing publication_status: published publisher: 'Society for Industrial and Applied Mathematics ' publist_id: '6186' pubrep_id: '811' quality_controlled: '1' scopus_import: 1 status: public title: Modular parameter identification of biomolecular networks type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 38 year: '2016' ...