Trends in Biotechnology
Volume 22, Issue 8, 1 August 2004, Pages 400-405
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Comparison of network-based pathway analysis methods

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Abstract

Network-based definitions of biochemical pathways have emerged in recent years. These pathway definitions insist on the balanced use of a whole network of biochemical reactions. Two such related definitions, elementary modes and extreme pathways, have generated novel hypotheses regarding biochemical network function. The relationship between these two approaches can be illustrated by comparing and contrasting the elementary modes and extreme pathways of previously published metabolic reconstructions of the human red blood cell (RBC) and the human pathogen Helicobacter pylori. Descriptions of network properties generated by using these two approaches in the analysis of realistic metabolic networks need careful interpretation.

Section snippets

Network-based pathway analysis

Biological networks can be represented by a stoichiometric matrix (S). The rows of S correspond to the compounds (e.g. metabolites) in a reaction network. The columns of S correspond to the reactions in a network, with elements corresponding to stoichiometric coefficients of the associated reactions. At steady state, mass balance in a network can be represented by the flux-balance equation:Sv=0where v is a vector whose elements correspond to fluxes through the associated reactions in S. The set

Results

Using Metatool [19] and FluxAnalyzer [20], we have calculated the elementary modes for the metabolic network models of H. pylori and the RBC for which the extreme pathways were previously calculated 17, 21. Thus, we can compare full sets of elementary modes and extreme pathways to illustrate the differences and similarities between the two sets. Below, the differences between these two network-based pathway definitions, as well as their relationship to each other, are discussed with regard to

Discussion

Elementary modes and extreme pathways are related network-based approaches that can be used to study biochemical networks. Although their development is still in its infancy, both methods have been used to study the properties of biochemical networks 8, 12. Here, we have applied the two approaches to metabolic networks of biologically meaningful size. The key results from this comparison are that (i) the elementary modes and extreme pathways are equivalent when all exchange fluxes are

Acknowledgements

We thank the Whitaker Foundation (Graduate Research Fellowship to J.P.) for financially supporting this work.

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