{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:16:56Z","timestamp":1778717816768,"version":"3.51.4"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Model development is a key task in systems biology, which typically starts from an initial model candidate and, involving an iterative cycle of hypotheses-driven model modifications, leads to new experimentation and subsequent model identification steps. The final product of this cycle is a satisfactory refined model of the biological phenomena under study. During such iterative model development, researchers frequently propose a set of model candidates from which the best alternative must be selected. Here we consider this problem of model selection and formulate it as a simultaneous model selection and parameter identification problem. More precisely, we consider a general mixed-integer nonlinear programming (MINLP) formulation for model selection and identification, with emphasis on dynamic models consisting of sets of either ODEs (ordinary differential equations) or DAEs (differential algebraic equations).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We solved the MINLP formulation for model selection and identification using an algorithm based on <jats:italic>Scatter Search<\/jats:italic> (SS). We illustrate the capabilities and efficiency of the proposed strategy with a case study considering the KdpD\/KdpE system regulating potassium homeostasis in <jats:italic>Escherichia coli<\/jats:italic>. The proposed approach resulted in a final model that presents a better fit to the <jats:italic>in silico<\/jats:italic> generated experimental data.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The presented MINLP-based optimization approach for nested-model selection and identification is a powerful methodology for model development in systems biology. This strategy can be used to perform model selection and parameter estimation in one single step, thus greatly reducing the number of experiments and computations of traditional modeling approaches.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-7-76","type":"journal-article","created":{"date-parts":[[2013,8,12]],"date-time":"2013-08-12T20:14:04Z","timestamp":1376338444000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Simultaneous model discrimination and parameter estimation in dynamic models of cellular systems"],"prefix":"10.1186","volume":"7","author":[{"given":"Maria","family":"Rodriguez-Fernandez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Rehberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Kremling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio R","family":"Banga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,8,12]]},"reference":[{"issue":"4","key":"1136_CR1","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1093\/bib\/bbl040","volume":"7","author":"NAW van Riel","year":"2006","unstructured":"van Riel NAW: Dynamic modelling and analysis of biochemical networks: mechanism-based models and model-based experiments. Brief Bioinform. 2006, 7 (4): 364-10.1093\/bib\/bbl040.","journal-title":"Brief Bioinform"},{"issue":"5","key":"1136_CR2","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.mib.2004.08.004","volume":"7","author":"J Stelling","year":"2004","unstructured":"Stelling J: Mathematical models in microbial systems biology. Curr Opin Microbiol. 2004, 7 (5): 513-518. 10.1016\/j.mib.2004.08.004.","journal-title":"Curr Opin Microbiol"},{"key":"1136_CR3","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1042\/bse0450195","volume":"45","author":"JR Banga","year":"2008","unstructured":"Banga JR, Balsa-Canto E: Parameter estimation and optimal experimental design. Essays Biochem. 2008, 45: 195-10.1042\/BSE0450195.","journal-title":"Essays Biochem"},{"issue":"11","key":"1136_CR4","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1038\/nrm2030","volume":"7","author":"K Jaqaman","year":"2006","unstructured":"Jaqaman K, Danuser G: Linking data to models: data regression. Nat Rev Mol Cell Biol. 2006, 7 (11): 813-819. 10.1038\/nrm2030.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"1136_CR5","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1111\/j.1742-4658.2008.06844.x","volume":"276","author":"M Ashyraliyev","year":"2008","unstructured":"Ashyraliyev M, Fomekong-Nanfack Y, Kaandorp JA, Blom JG: Systems biology: parameter estimation for biochemical models. FEBS J. 2008, 276 (4): 886-902.","journal-title":"FEBS J"},{"issue":"6912","key":"1136_CR6","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/nature01254","volume":"420","author":"H Kitano","year":"2002","unstructured":"Kitano H: Computational systems biology. Nature. 2002, 420 (6912): 206-210. 10.1038\/nature01254.","journal-title":"Nature"},{"issue":"4","key":"1136_CR7","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.cell.2005.04.020","volume":"121","author":"A Aderem","year":"2005","unstructured":"Aderem A: Systems biology: its practice and challenges. Cell. 2005, 121 (4): 511-513. 10.1016\/j.cell.2005.04.020.","journal-title":"Cell"},{"issue":"3","key":"1136_CR8","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.copbio.2005.04.004","volume":"16","author":"M Arita","year":"2005","unstructured":"Arita M, Robert M, Tomita M: All systems go: launching cell simulation fueled by integrated experimental biology data. Curr Opin Biotechnol. 2005, 16 (3): 344-349. 10.1016\/j.copbio.2005.04.004.","journal-title":"Curr Opin Biotechnol"},{"issue":"3","key":"1136_CR9","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1016\/S0006-3495(04)74201-0","volume":"86","author":"X Feng","year":"2004","unstructured":"Feng X, Rabitz H: Optimal identification of biochemical reaction networks. Biophys J. 2004, 86 (3): 1270-1281. 10.1016\/S0006-3495(04)74201-0.","journal-title":"Biophys J"},{"issue":"9","key":"1136_CR10","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1101\/gr.1226004","volume":"14","author":"A Kremling","year":"2004","unstructured":"Kremling A, Fischer S, Gadkar K, Doyle III FJ, Sauter T, Bullinger E, Gilles ED, Allgower F: A benchmark for methods in reverse engineering and model discrimination: problem formulation and solutions. Genome Res. 2004, 14 (9): 1773-10.1101\/gr.1226004.","journal-title":"Genome Res"},{"key":"1136_CR11","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/1471-2105-6-155","volume":"6","author":"KG Gadkar","year":"2005","unstructured":"Gadkar KG, Gunawan R, Doyle III FJ: Iterative approach to model identification of biological networks. BMC Bioinform. 2005, 6: 155-10.1186\/1471-2105-6-155.","journal-title":"BMC Bioinform"},{"key":"1136_CR12","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1752-0509-4-11","volume":"4","author":"E Balsa-Canto","year":"2010","unstructured":"Balsa-Canto E, Alonso A, Banga JR: An iterative identification procedure for dynamic modeling of biochemical networks. BMC Syst Biol. 2010, 4: 11-10.1186\/1752-0509-4-11.","journal-title":"BMC Syst Biol"},{"issue":"11","key":"1136_CR13","doi-asserted-by":"publisher","first-page":"e1000558","DOI":"10.1371\/journal.pcbi.1000558","volume":"5","author":"S Bandara","year":"2009","unstructured":"Bandara S, Schloeder JP, Eils R, Bock HG, Meyer T: Optimal experimental design for parameter estimation of a cell signaling model. PLoS Comput Biol. 2009, 5 (11): e1000558-10.1371\/journal.pcbi.1000558.","journal-title":"PLoS Comput Biol"},{"issue":"2","key":"1136_CR14","doi-asserted-by":"publisher","first-page":"e30","DOI":"10.1371\/journal.pcbi.0040030","volume":"4","author":"JF Apgar","year":"2008","unstructured":"Apgar JF, Toettcher JE, Endy D, White FM, Tidor B: Stimulus design for model selection and validation in cell signaling. PLoS Comput Biol. 2008, 4 (2): e30-10.1371\/journal.pcbi.0040030.","journal-title":"PLoS Comput Biol"},{"key":"1136_CR15","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/1752-0509-4-38","volume":"4","author":"B Melykuti","year":"2010","unstructured":"Melykuti B, August E, Papachristodoulou A, El-Samad H: Discriminating between rival biochemical network models: three approaches to optimal experiment design. BMC Syst Biol. 2010, 4: 38-10.1186\/1752-0509-4-38.","journal-title":"BMC Syst Biol"},{"issue":"7","key":"1136_CR16","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1093\/bioinformatics\/btq074","volume":"26","author":"D Skanda","year":"2010","unstructured":"Skanda D, Lebiedz D: An optimal experimental design approach to model discrimination in dynamic biochemical systems. Bioinform. 2010, 26 (7): 939-945. 10.1093\/bioinformatics\/btq074.","journal-title":"Bioinform"},{"issue":"3","key":"1136_CR17","doi-asserted-by":"publisher","first-page":"e1000696","DOI":"10.1371\/journal.pcbi.1000696","volume":"6","author":"G Lillacci","year":"2010","unstructured":"Lillacci G, Khammash M: Parameter estimation and model selection in computational biology. PLoS Comput Biol. 2010, 6 (3): e1000696-10.1371\/journal.pcbi.1000696.","journal-title":"PLoS Comput Biol"},{"key":"1136_CR18","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S1570-7946(03)80071-8","volume":"16","author":"PJT Verheijen","year":"2003","unstructured":"Verheijen PJT: Model selection: an overview of practices in chemical engineering. Comput Aided Chem Eng. 2003, 16: 85-104.","journal-title":"Comput Aided Chem Eng"},{"issue":"4","key":"1136_CR19","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1002\/aic.690450418","volume":"45","author":"L Petzold","year":"1999","unstructured":"Petzold L, Zhu W: Model reduction for chemical kinetics: An optimization approach. AIChE J. 1999, 45 (4): 869-886. 10.1002\/aic.690450418.","journal-title":"AIChE J"},{"key":"1136_CR20","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S0098-1354(00)00311-2","volume":"24","author":"K Edwards","year":"2000","unstructured":"Edwards K, Edgar TF, Manousiouthakis VI: Reaction mechanism simplification using mixed-integer nonlinear programming. Comput Chem Eng. 2000, 24: 67-79. 10.1016\/S0098-1354(00)00311-2.","journal-title":"Comput Chem Eng"},{"key":"1136_CR21","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1049\/iet-syb:20080098","volume":"3","author":"MR Maurya","year":"2009","unstructured":"Maurya MR, Bornheimer SJ, Venkatasubramanian V, Subramaniam S: Mixed-integer nonlinear optimisation approach to coarse-graining biochemical networks. IET Syst Biol. 2009, 3: 24-10.1049\/iet-syb:20080098.","journal-title":"IET Syst Biol"},{"issue":"1","key":"1136_CR22","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.ymben.2009.08.010","volume":"12","author":"EV Nikolaev","year":"2010","unstructured":"Nikolaev EV: The elucidation of metabolic pathways and their improvements using stable optimization of large-scale kinetic models of cellular systems. Metab Eng. 2010, 12 (1): 26-38. 10.1016\/j.ymben.2009.08.010.","journal-title":"Metab Eng"},{"key":"1136_CR23","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1752-0509-2-47","volume":"2","author":"JR Banga","year":"2008","unstructured":"Banga JR: Optimization in computational systems biology. BMC Syst Biol. 2008, 2: 47-10.1186\/1752-0509-2-47.","journal-title":"BMC Syst Biol"},{"issue":"3","key":"1136_CR24","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1214\/ss\/1030037906","volume":"12","author":"J Aldrich","year":"1997","unstructured":"Aldrich J: R. A. Fisher and the making of maximum likelihood 1912-1922. Stat Sci. 1997, 12 (3): 162-176.","journal-title":"Stat Sci"},{"issue":"6","key":"1136_CR25","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1109\/TAC.1974.1100705","volume":"19","author":"H Akaike","year":"1974","unstructured":"Akaike H: A new look at the statistical model identification. IEEE Trans Automatic Control. 1974, 19 (6): 716-723. 10.1109\/TAC.1974.1100705.","journal-title":"IEEE Trans Automatic Control"},{"issue":"4","key":"1136_CR26","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1111\/j.1742-4658.2008.06845.x","volume":"276","author":"G Cedersund","year":"2009","unstructured":"Cedersund G, Roll J: Systems biology: model based evaluation and comparison of potential explanations for given biological data. FEBS J. 2009, 276 (4): 903-922. 10.1111\/j.1742-4658.2008.06845.x.","journal-title":"FEBS J"},{"issue":"3","key":"1136_CR27","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.ecolmodel.2009.10.021","volume":"221","author":"CP McDonald","year":"2010","unstructured":"McDonald CP, Urban NR: Using a model selection criterion to identify appropriate complexity in aquatic biogeochemical models. Ecol Model. 2010, 221 (3): 428-432. 10.1016\/j.ecolmodel.2009.10.021.","journal-title":"Ecol Model"},{"issue":"2-3","key":"1136_CR28","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.biosystems.2005.06.016","volume":"83","author":"M Rodriguez-Fernandez","year":"2006","unstructured":"Rodriguez-Fernandez M, Mendes P, Banga JR: A hybrid approach for efficient and robust parameter estimation in biochemical pathways. Biosyst. 2006, 83 (2-3): 248-265. 10.1016\/j.biosystems.2005.06.016.","journal-title":"Biosyst"},{"key":"1136_CR29","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s10898-006-9075-3","volume":"37","author":"JA Egea","year":"2007","unstructured":"Egea JA, Rodriguez-Fernandez M, Banga JR, Mart\u00ed R: Scatter Search for Chemical and Bio-Process Optimization. J Glob Optimization. 2007, 37: 481-503. 10.1007\/s10898-006-9075-3.","journal-title":"J Glob Optimization"},{"issue":"7","key":"1136_CR30","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1016\/j.cor.2008.08.015","volume":"36","author":"M Schl\u00fcter","year":"2009","unstructured":"Schl\u00fcter M, Egea JA, Banga JR: Extended ant colony optimization for non-convex mixed integer nonlinear programming. Comput Oper Res. 2009, 36 (7): 2217-2229. 10.1016\/j.cor.2008.08.015.","journal-title":"Comput Oper Res"},{"issue":"2","key":"1136_CR31","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.cor.2009.05.003","volume":"37","author":"JA Egea","year":"2010","unstructured":"Egea JA, Banga JR, Mart\u00ed R: An evolutionary method for complex-process optimization. Comput Oper Res. 2010, 37 (2): 315-324. 10.1016\/j.cor.2009.05.003.","journal-title":"Comput Oper Res"},{"issue":"3","key":"1136_CR32","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s11590-006-0026-1","volume":"1","author":"O Exler","year":"2007","unstructured":"Exler O, Schittkowski K: A trust region SQP algorithm for mixed-integer nonlinear programming. Optimization Lett. 2007, 1 (3): 269-280. 10.1007\/s11590-006-0026-1.","journal-title":"Optimization Lett"},{"key":"1136_CR33","volume-title":"A collection of 186 test problems for nonlinear mixed-integer programming","author":"K Schittkowski","year":"2012","unstructured":"Schittkowski K: A collection of 186 test problems for nonlinear mixed-integer programming. 2012, Tech. rep., Department of Computer Science; University of Bayreuth"},{"issue":"4","key":"1136_CR34","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/s12532-012-0045-0","volume":"4","author":"O Exler","year":"2012","unstructured":"Exler O, Lehmann T, Schittkowski K: A comparative study of SQP-type algorithms for nonlinear and nonconvex mixed-integer optimization. Math Program Comput. 2012, 4 (4): 383-412. 10.1007\/s12532-012-0045-0.","journal-title":"Math Program Comput"},{"issue":"4","key":"1136_CR35","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1080\/10556780903027500","volume":"25","author":"M Diehl","year":"2010","unstructured":"Diehl M, Walther A, Bock HG, Kostina E: An adjoint-based SQP algorithm with quasi-Newton Jacobian updates for inequality constrained optimization. Optimization Methods Softw. 2010, 25 (4): 531-552. 10.1080\/10556780903027500.","journal-title":"Optimization Methods Softw"},{"issue":"15","key":"1136_CR36","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1093\/bioinformatics\/btp358","volume":"25","author":"A Raue","year":"2009","unstructured":"Raue A, Kreutz C, Maiwald T, Bachmann J, Schilling M, Klingmueller U, Timmer J: Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood. Bioinform. 2009, 25 (15): 1923-1929. 10.1093\/bioinformatics\/btp358.","journal-title":"Bioinform"},{"issue":"8","key":"1136_CR37","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1093\/bioinformatics\/bts088","volume":"28","author":"J Vanlier","year":"2012","unstructured":"Vanlier J, Tiemann CA, Hilbers PAJ, van Riel NAW: An integrated strategy for prediction uncertainty analysis. Bioinform. 2012, 28 (8): 1130-1135. 10.1093\/bioinformatics\/bts088.","journal-title":"Bioinform"},{"issue":"26","key":"1136_CR38","doi-asserted-by":"publisher","first-page":"20171","DOI":"10.1074\/jbc.M110.106849","volume":"285","author":"C Brannmark","year":"2010","unstructured":"Brannmark C, Palmer R, Glad ST, Cedersund G, Stralfors P: Mass and information feedbacks through receptor endocytosis govern insulin signaling as revealed using a parameter-free modeling framework. J Biol Chem. 2010, 285 (26): 20171-20179. 10.1074\/jbc.M110.106849.","journal-title":"J Biol Chem"},{"issue":"10","key":"1136_CR39","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1002\/rnc.2797","volume":"22","author":"M Rodriguez-Fernandez","year":"2012","unstructured":"Rodriguez-Fernandez M, Banga JR, Doyle III FJ: Novel global sensitivity analysis methodology accounting for the crucial role of the distribution of input parameters: application to systems biology models. Int J Robust Nonlinear Control. 2012, 22 (10): 1082-1102. 10.1002\/rnc.2797.","journal-title":"Int J Robust Nonlinear Control"},{"key":"1136_CR40","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/0025-5564(85)90098-7","volume":"77","author":"JA Jacquez","year":"1985","unstructured":"Jacquez JA, Greif P: Numerical Parameter Identifiability and estimability: integrating identifiability, estimability, and optimal sampling desing. Math Biosci. 1985, 77: 201-227. 10.1016\/0025-5564(85)90098-7.","journal-title":"Math Biosci"},{"issue":"1","key":"1136_CR41","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1109\/10.900248","volume":"48","author":"S Audoly","year":"2001","unstructured":"Audoly S, Bellu G, D\u2019Angio L, Saccomani MP, Cobelli C: Global identifiability of nonlinear models of biological systems. IEEE Trans Biomed Eng. 2001, 48 (1): 55-65. 10.1109\/10.900248.","journal-title":"IEEE Trans Biomed Eng"},{"issue":"3","key":"1136_CR42","doi-asserted-by":"publisher","first-page":"431","DOI":"10.2307\/1909470","volume":"27","author":"F Fisher","year":"1959","unstructured":"Fisher F: Econometrica. 1959, 27 (3): 431-447. 10.2307\/1909470.","journal-title":"Econometrica"},{"key":"1136_CR43","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1029\/2000WR900350","volume":"37","author":"R Brun","year":"2001","unstructured":"Brun R, Reichert P, Kunsch HR: Practical identifiability analysis of large environmental simulation models. Water Resour Res. 2001, 37: 1015-1030. 10.1029\/2000WR900350.","journal-title":"Water Resour Res"},{"issue":"2","key":"1136_CR44","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1109\/21.229461","volume":"23","author":"WJ Karnavas","year":"1993","unstructured":"Karnavas WJ, Sanchez P, Bahill AT: Sensitivity analyses of continuous and discrete systems in the time and frequency domains. IEEE Trans Syst, Man, Cybern. 1993, 23 (2): 488-501. 10.1109\/21.229461.","journal-title":"IEEE Trans Syst, Man, Cybern"},{"key":"1136_CR45","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/j.ress.2008.05.006","volume":"94","author":"S Kucherenko","year":"2009","unstructured":"Kucherenko S, Rodriguez-Fernandez M, Pantelides C, Shah N: Monte Carlo evaluation of derivative based global sensitivity measures. Reliability Eng Syst Saf. 2009, 94: 1135-1148. 10.1016\/j.ress.2008.05.006.","journal-title":"Reliability Eng Syst Saf"},{"issue":"13","key":"1136_CR46","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1093\/bioinformatics\/btq242","volume":"26","author":"M Rodriguez-Fernandez","year":"2010","unstructured":"Rodriguez-Fernandez M, Banga JR: SensSB: A software toolbox for the development and sensitivity analysis of systems biology models. Bioinform. 2010, 26 (13): 1675-1676. 10.1093\/bioinformatics\/btq242.","journal-title":"Bioinform"},{"issue":"1-3","key":"1136_CR47","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.biosystems.2004.06.003","volume":"78","author":"A Kremling","year":"2004","unstructured":"Kremling A, Heermann R, Centler F, Jung K, Gilles ED: Analysis of two-component signal transduction by mathematical modeling using the KdpD\/KdpE system of Escherichia coli. Biosyst. 2004, 78 (1-3): 23-37. 10.1016\/j.biosystems.2004.06.003.","journal-title":"Biosyst"},{"key":"1136_CR48","volume-title":"An Introduction to Systems Biology - Design Principles of Biological Circuits","author":"U Alon","year":"2007","unstructured":"Alon U: An Introduction to Systems Biology - Design Principles of Biological Circuits. 2007, London: Chapman & Hall\/CRC"},{"issue":"3","key":"1136_CR49","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.jtbi.2007.01.004","volume":"246","author":"S Widder","year":"2007","unstructured":"Widder S, Schicho J, Schuster P: Dynamic patterns of gene regulation I: Simple two-gene systems. J Theor Biol. 2007, 246 (3): 395-419. 10.1016\/j.jtbi.2007.01.004.","journal-title":"J Theor Biol"},{"key":"1136_CR50","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1742-4682-7-40","volume":"7","author":"Z Konkoli","year":"2010","unstructured":"Konkoli Z: A danger of low copy numbers for inferring incorrect cooperativity degree. Theor Biol Med Model. 2010, 7: 40-10.1186\/1742-4682-7-40.","journal-title":"Theor Biol Med Model"},{"issue":"2","key":"1136_CR51","doi-asserted-by":"publisher","first-page":"e9202","DOI":"10.1371\/journal.pone.0009202","volume":"5","author":"R Prill","year":"2010","unstructured":"Prill R, Marbach D, Saez-Rodriguez J, Sorger P, Alexopoulos L, Xue X, Clarke N, Altan-Bonnet G, Stolovitzky G: Towards a rigorous assessment of systems biology models: the DREAM3 challenges. PloS one. 2010, 5 (2): e9202-10.1371\/journal.pone.0009202.","journal-title":"PloS one"},{"key":"1136_CR52","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/1752-0509-5-177","volume":"5","author":"G Szederkenyi","year":"2011","unstructured":"Szederkenyi G, Banga JR, Alonso AA: Inference of complex biological networks: distinguishability issues and optimization-based solutions. BMC Syst Biol. 2011, 5: 177-10.1186\/1752-0509-5-177.","journal-title":"BMC Syst Biol"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-7-76.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T01:11:55Z","timestamp":1630545115000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-7-76"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,12]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["1136"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-7-76","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,12]]},"assertion":[{"value":"8 May 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"76"}}