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Chasing the flux: selecting target pathways through flux analysis of carbon metabolism
SIMEONIDIS, Vangelis; Murabito, Ettore; Smallbone, Kieran et al.
20111st Conference on Constraint-based Reconstruction and Analysis
 

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Keywords :
metabolic flux; metabolic modelling; carbon metabolism
Abstract :
[en] One of the goals of Systems Biology is to develop and utilise high-throughput methods for the measurement of parameters and concentrations on a genome-wide scale, while at the same time generating predictive models for system behaviour. In studying genome-scale metabolic networks, the task of exhaustively assaying and measuring all reaction components can be daunting, because hundreds or even thousands of enzymes (activities and concentrations) need to be considered for the construction of a full-scale, detailed model. There is a clear need for strategies that allow us to systematically select the subsets of pathways and reactions which should be prioritized when studying metabolism. We present a methodology for selecting those reactions that carry the overwhelming majority of the carbon flux through the metabolic network. The recent community-driven reconstruction of the metabolic network of baker’s yeast [1] provides the basis for our analysis. Flux Balance Analysis provides a theoretical flux distribution. Results are constrained with GC-MS exometabolomic measurements of the carbon flux. Flux calculations can also be improved by using 13C measurements to determine intracellular metabolic fluxes. The solution of the constrained FBA problem gives us a ranked list of reactions, based on the amount of carbon flux through each reaction. We improve the specificity of the method further by performing an Elementary Flux Mode analysis, which provides us with target pathways consisting of the reactions that carry the most carbon flux. Our methodology allows us to cover more than 95% of the carbon flux by studying but a small subset of the reactions of the genome-scale metabolic network of baker’s yeast.
Research center :
Manchester Centre for Integrative Systems Biology
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
SIMEONIDIS, Vangelis ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) ; University of Manchester
Murabito, Ettore
Smallbone, Kieran
Dunn, Warwick
Winder, Catherine
Swainston, Neil
Mendes, Pedro
Westerhoff, Hans V.
Language :
English
Title :
Chasing the flux: selecting target pathways through flux analysis of carbon metabolism
Publication date :
26 June 2011
Number of pages :
33x47in
Event name :
1st Conference on Constraint-based Reconstruction and Analysis
Event organizer :
University of Iceland
Event place :
Reykjavik, Iceland
Event date :
24th - 26th June 2011
Audience :
International
Additional URL :
Name of the research project :
Manchester Centre for Integrative Systems Biology
Funders :
BBSRC - Biotechnology and Biological Sciences Research Council [GB]
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since 18 June 2013

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