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Achcar2012 - Glycolysis in bloodstream form T. brucei


ABSTRACT: Achcar2012 - Glycolysis in bloodstream form T. brucei Kinetic models of metabolism require quantitative knowledge of detailed kinetic parameters. However, the knowledge about these parameters is often uncertain. An analysis of the effect of parameter uncertainties on a particularly well defined example of a quantitative metablic model, the model of glycolysis in bloodstream form Trypanosoma brucei , has been presented here. This model is described in the article: Dynamic modelling under uncertainty: the case of Trypanosoma brucei energy metabolism. Achcar F, Kerkhoven EJ; SilicoTryp Consortium, Bakker BM, Barrett MP, Breitling R. PLoS Comput Biol. 2012 Jan; 8(1):e1002352. Abstract: Kinetic models of metabolism require detailed knowledge of kinetic parameters. However, due to measurement errors or lack of data this knowledge is often uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei is a particularly well analysed example of a quantitative metabolic model, but so far it has been studied with a fixed set of parameters only. Here we evaluate the effect of parameter uncertainty. In order to define probability distributions for each parameter, information about the experimental sources and confidence intervals for all parameters were collected. We created a wiki-based website dedicated to the detailed documentation of this information: the SilicoTryp wiki (http://silicotryp.ibls.gla.ac.uk/wiki/Glycolysis). Using information collected in the wiki, we then assigned probability distributions to all parameters of the model. This allowed us to sample sets of alternative models, accurately representing our degree of uncertainty. Some properties of the model, such as the repartition of the glycolytic flux between the glycerol and pyruvate producing branches, are robust to these uncertainties. However, our analysis also allowed us to identify fragilities of the model leading to the accumulation of 3-phosphoglycerate and/or pyruvate. The analysis of the control coefficients revealed the importance of taking into account the uncertainties about the parameters, as the ranking of the reactions can be greatly affected. This work will now form the basis for a comprehensive Bayesian analysis and extension of the model considering alternative topologies. This model is hosted on BioModels Database and identified by: MODEL1209130000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Lukas Endler  

PROVIDER: BIOMD0000000428 | BioModels | 2012-11-20

REPOSITORIES: BioModels

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Publications

Dynamic modelling under uncertainty: the case of Trypanosoma brucei energy metabolism.

Achcar Fiona F   Kerkhoven Eduard J EJ   Bakker Barbara M BM   Barrett Michael P MP   Breitling Rainer R  

PLoS computational biology 20120119 1


Kinetic models of metabolism require detailed knowledge of kinetic parameters. However, due to measurement errors or lack of data this knowledge is often uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei is a particularly well analysed example of a quantitative metabolic model, but so far it has been studied with a fixed set of parameters only. Here we evaluate the effect of parameter uncertainty. In order to define probability distributions for each parameter, inf  ...[more]

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