Abstract
A method to calibrate stoichiometric coefficients values related to uncharacterized or lumped reactions of metabolic network models is presented. The method finds coefficients values that produce a model version that best fits multivariable experimental data. The method was tested with a metabolic network of 44 metabolites and 49 stoichiometric reactions, with four reactions having undetermined stoichiometric coefficients values. A total of 1320 model versions with different combinations of stoichiometric coefficient values were generated. Experimental data was used to produce a calibration curve and different fitness scores were used to evaluate the accuracy of flux balance analysis (FBA) simulations of these model versions to reproduce the experimental data. The model version with highest fitness to the experimental data was found using Mean Relative Error (MRE) scores and auto-scaled transformation of estimated datasets.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Durot, M., Bourguignon, P., Schachter, V.: Genome-scale models of bacterial metabolism: Reconstruction and applications. FEMS Microbiol. Rev. 33, 164–190 (2009)
Edwards, J.S., Ibarra, R.U., Palsson, B.: In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data. Nat. Biotechnol. 19, 125–130 (2001)
Feist, A.M., Herrgård, M.J., Thiele, I., Reed, J.L., Palsson, B.: Reconstruction of bio-chemical networks in microorganisms. Nature Reviews Microbiology 7, 129–143 (2009)
Kümmel, A., Panke, S., Heinemann, M.: Putative regulatory sites unraveled by network-embedded thermodynamic analysis of metabolome data. Molecular Systems Biology 2 (2006a)
Lewis, N.E., Hixson, K.K., Conrad, T.M., Lerman, J.A., Charusanti, P., Polpitiya, A.D., Adkins, J.N., Schramm, G., Purvine, S.O., Lopez-Ferrer, D., Weitz, K.K., Eils, R., König, R., Smith, R.D., Palsson, B.Ø.: Omic data from evolved E. coli are consistent with computed optimal growth from genome-scale models. Molecular Systems Biology 6 (2010)
Makinia, J.: Mathematical Modelling and Computer Simulation of Activated Sludge Systems. IWA Publishing, London (2010)
Oberhardt, M.A., Chavali, A.K., Papin, J.: Flux balance analysis: Interrogating genome-scale metabolic networks. Methods in Molecular Biology 500, 61–80 (2009)
Orth, J.D., Thiele, I., Palsson, B.: What is flux balance analysis? Nat. Biotechnol. 28, 245–248 (2010)
Sauer, U.: Metabolic networks in motion: 13C-based flux analysis. Molecular Systems Biology 2 (2006)
Schellenberger, J., Que, R., Fleming, R.M.T., Thiele, I., Orth, J.D., Feist, A.M., Zielinski, D.C., Bord-bar, A., Lewis, N.E., Rahmanian, S., Kang, J., Hyduke, D.R., Palsson, B.Ø.: Quantitative prediction of cellular metabolism with constraint-based models: The COBRA Toolbox v2.0. Nature Protocols 6, 1290–1307 (2011)
Schuetz, R., Kuepfer, L., Sauer, U.: Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli. Molecular Systems Biology 3 (2007)
Thiele, I., Palsson, B.Ø.: A protocol for generating a high-quality genome-scale metabolic reconstruction. Nature Protocols 5, 93–121 (2010)
Vadivelu, V.M., Keller, J., Yuan, Z.: Stoichiometric and kinetic characterisation of Nitrosomonas sp. in mixed culture by decoupling the growth and energy generation processes. J. Biotechnol. 126, 342–356 (2006)
van den Berg, R.A., Hoefsloot, H.C.J., Westerhuis, J.A., Smilde, A.K., van der Werf, M.: Centering, scaling, and transformations: Improving the biological information content of metabolomics data. BMC Genomics 7 (2006)
Varma, A., Palsson, B.: Metabolic flux balancing: Basic concepts, scientific and practical use. Bio/Technology 12, 994–998 (1994)
Whittaker, M., Bergmann, D., Arciero, D., Hooper, A.: Electron transfer during the oxidation of ammonia by the chemolithotrophic bacterium Nitrosomonas europaea. Biochimica et Biophysica Acta - Bioenergetics 1459, 346–355 (2000)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer International Publishing Switzerland
About this paper
Cite this paper
Perez-Garcia, O., Villas-Boas, S., Singhal, N. (2014). A Method to Calibrate Metabolic Network Models with Experimental Datasets. In: Saez-Rodriguez, J., Rocha, M., Fdez-Riverola, F., De Paz Santana, J. (eds) 8th International Conference on Practical Applications of Computational Biology & Bioinformatics (PACBB 2014). Advances in Intelligent Systems and Computing, vol 294. Springer, Cham. https://doi.org/10.1007/978-3-319-07581-5_22
Download citation
DOI: https://doi.org/10.1007/978-3-319-07581-5_22
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-07580-8
Online ISBN: 978-3-319-07581-5
eBook Packages: EngineeringEngineering (R0)