Evaluating the integration of proteomic data for the prediction of intracellular fluxes after knockout experiments

Rafael S. Costa, Daniel Machado, Eugénio C. Ferreira, Isabel Rocha

Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsResearchpeer-review

Abstract

So far, few large scale kinetic models of metabolic networks have been successfully constructed. The main reasons for this are not only the associated mathematical complexity, but also the large number of unknown kinetic parameters required in the rate equations to define the system. In contrast to kinetic models, the constraint-based modelling approach bypasses these difficulties by using basically only stoichiometric information with certain physicochemical constraints to delimit the solution space without large fitted parameter sets. Although these constraintbased models are highly relevant to predict feasible steady-state fluxes under a diverse range of genetic and environmental conditions, the steady-state assumption may oversimplify cellular behaviour and cannot predict time-course profiles. To overcome these problems, combining these two approaches appears as a reasonable alternative to modelling large-scale metabolic networks. On the other hand, several of the experimental data required for model construction are often rare and in this way it is usually assumed that the enzyme concentrations are constant. In this work, we used a central carbon metabolic network of E. coli to investigate whether including high throughput enzyme concentration data into a kinetic model allows improved predictions of metabolic flux distributions in response to single knockouts perturbations. For this purpose, an E. coli model, based on results obtained from flux balance analysis (FBA) and approximate lin-log kinetics was constructed. The intracellular fluxes distributions, obtained using this model, were compared with published in vivo measurements. © 2010 IFAC.
Original languageEnglish
Title of host publicationIFAC Proceedings of 11th International Symposium on Computer Applications in Biotechnology
Volume11
Publication date2010
Pages114-119
ISBN (Print)9783902661708
DOIs
Publication statusPublished - 2010
Externally publishedYes
Event11th International Symposium on Computer Applications in Biotechnology - Leuven, Belgium
Duration: 5 Jul 20107 Jul 2010
Conference number: 11
http://www.cab2010.org/

Conference

Conference11th International Symposium on Computer Applications in Biotechnology
Number11
CountryBelgium
CityLeuven
Period05/07/201007/07/2010
Internet address
SeriesIFAC Proceedings Volumes (IFAC-PapersOnline)

Cite this

Costa, R. S., Machado, D., Ferreira, E. C., & Rocha, I. (2010). Evaluating the integration of proteomic data for the prediction of intracellular fluxes after knockout experiments. In IFAC Proceedings of 11th International Symposium on Computer Applications in Biotechnology (Vol. 11, pp. 114-119). IFAC Proceedings Volumes (IFAC-PapersOnline) https://doi.org/10.3182/20100707-3-BE-2012.0108