title: System estimation from metabolic time-series data.
abstract: At the center of computational systems biology are mathematical models that capture the dynamics of biological systems and offer novel insights. The bottleneck in the construction of these models is presently the identification of model parameters that make the model consistent with observed data. Dynamic flux estimation (DFE) is a novel methodological framework for estimating parameters for models of metabolic systems from time-series data. DFE consists of two distinct phases, an entirely model-free and assumption-free data analysis and a model-based mathematical characterization of process representations. The model-free phase reveals inconsistencies within the data, and between data and the alleged system topology, while the model-based phase allows quantitative diagnostics of whether--or to what degree--the assumed mathematical formulations are appropriate or in need of improvement. Hallmarks of DFE are the facility to: diagnose data and model consistency; circumvent undue compensation of errors; determine functional representations of fluxes uncontaminated by errors in other fluxes and pinpoint sources of remaining errors. Our results suggest that the proposed approach is more effective and robust than presently available methods for deriving metabolic models from time-series data. Its avoidance of error compensation among process descriptions promises significantly improved extrapolability toward new data or experimental conditions.
authors.affiliation: Integrative BioSystems Institute and The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Goel
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Chou
authors.forename: Eberhard O
authors.initials: EO
authors.lastname: Voit
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D020543:Proteome / Q000378:metabolism; D012984:Software; D049490:Systems Biology
chemical_list: D020543:Proteome
references.citation: Bull Math Biol. 1996 Sep;58(5):923-38
references.pmid: 8837524
references.citation: Science. 2007 Apr 27;316(5824):593-7
references.pmid: 17379776
references.citation: IEEE/ACM Trans Comput Biol Bioinform. 2007 Oct-Dec;4(4):634-47
references.pmid: 17975274
references.citation: Theor Biol Med Model. 2006 Jul 19;3:25
references.pmid: 16854227
references.citation: Bioinformatics. 2004 Jul 22;20(11):1670-81
references.pmid: 14988125
references.citation: Microbiology (Reading). 2004 Apr;150(Pt 4):1103-1111
references.pmid: 15073320
references.citation: J Proteome Res. 2008 Jul;7(7):2595-604
references.pmid: 18442284
references.citation: Bioinformatics. 2006 Jul 1;22(13):1631-40
references.pmid: 16585066
references.citation: In Silico Biol. 2005;5(2):83-92
references.pmid: 15972008
references.citation: Appl Environ Microbiol. 2002 Dec;68(12):6332-42
references.pmid: 12450858
references.citation: J Biol Chem. 2002 Aug 2;277(31):28088-98
references.pmid: 12011086
references.citation: Antonie Van Leeuwenhoek. 2002 Aug;82(1-4):249-61
references.pmid: 12369191
references.citation: Neurochem Int. 2008 Feb;52(3):478-86
references.pmid: 17904693
references.citation: Syst Biol (Stevenage). 2006 Jul;153(4):286-98
references.pmid: 16986630
references.citation: BMC Syst Biol. 2008 Apr 16;2:35
references.pmid: 18416837
references.citation: Bioinformatics. 2003 Mar 22;19(5):643-50
references.pmid: 12651723
references.citation: Appl Environ Microbiol. 2004 Mar;70(3):1466-74
references.pmid: 15006767
references.citation: Biotechnol Bioeng. 1999 Jul 20;64(2):200-12
references.pmid: 10397856
references.citation: Eur J Biochem. 2000 Jun;267(12):3859-68
references.pmid: 10849005
references.citation: Bioinformatics. 2005 Apr 1;21(7):1180-8
references.pmid: 15513993
references.citation: Phytochemistry. 2007 Aug-Sep;68(16-18):2320-9
references.pmid: 17532017
references.citation: FEMS Microbiol Rev. 2005 Aug;29(3):531-54
references.pmid: 15939503
references.citation: Microbiology (Reading). 2002 Nov;148(Pt 11):3467-3476
references.pmid: 12427938
references.citation: Theor Biol Med Model. 2007 May 20;4:19
references.pmid: 17511884
references.citation: Microb Cell Fact. 2007 Feb 07;6:6
references.pmid: 17286851
references.citation: J Biosci Bioeng. 2002;93(1):78-87
references.pmid: 16233169
references.citation: J Bioinform Comput Biol. 2006 Apr;4(2):503-14
references.pmid: 16819798
references.citation: Genome Inform. 2003;14:114-23
references.pmid: 15706526
references.citation: Bioinformatics. 2007 Feb 15;23(4):480-6
references.pmid: 17038344
references.citation: BMC Bioinformatics. 2007 Aug 21;8:305
references.pmid: 17711581
references.citation: IET Syst Biol. 2007 May;1(3):174-80
references.pmid: 17591176
references.citation: J Bacteriol. 2003 May;185(9):2692-9
references.pmid: 12700248
references.citation: Bioinformatics. 2005 Apr 1;21(7):1154-63
references.pmid: 15514004