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Briefings in Bioinformatics Advance Access published online on March 15, 2009
Briefings in Bioinformatics, doi:10.1093/bib/bbp011
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© The Author 2009. Published by Oxford University Press. For Permissions, please email: journals.permissions@oxfordjournals.org

Flux balance analysis of biological systems: applications and challenges

Karthik Raman and Nagasuma Chandra

Corresponding author. Nagasuma Chandra, Bioinformatics Centre and Supercomputer Education and Research Centre, Indian Institute of Science, Bangalore 560012, India. Tel: +91-80-2293-2892; E-mail: nchandra{at}serc.iisc.ernet.in

Systems level modelling and simulations of biological processes are proving to be invaluable in obtaining a quantitative and dynamic perspective of various aspects of cellular function. In particular, constraint-based analyses of metabolic networks have gained considerable popularity for simulating cellular metabolism, of which flux balance analysis (FBA), is most widely used. Unlike mechanistic simulations that depend on accurate kinetic data, which are scarcely available, FBA is based on the principle of conservation of mass in a network, which utilizes the stoichiometric matrix and a biologically relevant objective function to identify optimal reaction flux distributions. FBA has been used to analyse genome-scale reconstructions of several organisms; it has also been used to analyse the effect of perturbations, such as gene deletions or drug inhibitions in silico. This article reviews the usefulness of FBA as a tool for gaining biological insights, advances in methodology enabling integration of regulatory information and thermodynamic constraints, and finally addresses the challenges that lie ahead. Various use scenarios and biological insights obtained from FBA, and applications in fields such metabolic engineering and drug target identification, are also discussed. Genome-scale constraint-based models have an immense potential for building and testing hypotheses, as well as to guide experimentation.

Keywords: network reconstruction, metabolic network analysis, objective functions, genome scale modelling, reactome modelling

Submitted: November 28, 2008. Received (in revised form): February 6, 2009.


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