Network-level analysis of metabolic regulation in the human red blood cell using random sampling and singular value decomposition

Christian L. Barrett, Nathan D. Price, Bernhard O. Palsson

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Extreme pathways (ExPas) have been shown to be valuable for studying the functions and capabilities of metabolic networks through characterization of the null space of the stoichiometric matrix (S). Singular value decomposition (SVD) of the ExPa matrix P has previously been used to characterize the metabolic regulatory problem in the human red blood cell (hRBC) from a network perspective. The calculation of ExPas is NP-hard, and for genome-scale networks the computation of ExPas has proven to be infeasible. Therefore an alternative approach is needed to reveal regulatory properties of steady state solution spaces of genome-scale stoichiometric matrices. Results: We show that the SVD of a matrix (W) formed of random samples from the steady-state solution space of the hRBC metabolic network gives similar insights into the regulatory properties of the network as was obtained with SVD of P. This new approach has two main advantages. First, it works with a direct representation of the shape of the metabolic solution space without the confounding factor of a non-uniform distribution of the extreme pathways and second, the SVD procedure can be applied to a very large number of samples, such as will be produced from genome-scale networks. Conclusion: These results show that we are now in a position to study the network aspects of the regulatory problem in genome-scale metabolic networks through the use of random sampling.

Original languageEnglish (US)
Article number132
JournalBMC Bioinformatics
Volume7
DOIs
StatePublished - Mar 13 2006
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

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