Flux balance analysis: interrogating genome-scale metabolic networks.

Flux balance analysis (FBA) is a computational method to analyze reconstructions of biochemical networks. FBA requires the formulation of a biochemical network in a precise mathematical framework called a stoichiometric matrix. An objective function is defined (e.g., growth rate) toward which the system is assumed to be optimized. In this chapter, we present the methodology, theory, and common pitfalls of the application of FBA.

[1]  B. Palsson,et al.  Expanded Metabolic Reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an In Silico Genome-Scale Characterization of Single- and Double-Deletion Mutants , 2005, Journal of bacteriology.

[2]  Anne Kümmel,et al.  In silico genome-scale reconstruction and validation of the Staphylococcus aureus metabolic network. , 2005, Biotechnology and bioengineering.

[3]  Kenneth J. Kauffman,et al.  Advances in flux balance analysis. , 2003, Current opinion in biotechnology.

[4]  B. Palsson,et al.  Metabolic Capabilities of Escherichia coli II. Optimal Growth Patterns , 1993 .

[5]  S. Schuster,et al.  Metabolic network structure determines key aspects of functionality and regulation , 2002, Nature.

[6]  Markus J. Herrgård,et al.  Integrated analysis of regulatory and metabolic networks reveals novel regulatory mechanisms in Saccharomyces cerevisiae. , 2006, Genome research.

[7]  T Zhu,et al.  A metabolic network analysis & NMR experiment design tool with user interface-driven model construction for depth-first search analysis. , 2003, Metabolic engineering.

[8]  C. Francke,et al.  Reconstructing the metabolic network of a bacterium from its genome. , 2005, Trends in microbiology.

[9]  R. Mahadevan,et al.  The effects of alternate optimal solutions in constraint-based genome-scale metabolic models. , 2003, Metabolic engineering.

[10]  Robert Urbanczik.  SNA – a toolbox for the stoichiometric analysis of metabolic networks , 2005, BMC Bioinformatics.

[11]  R. Sharan,et al.  A genome-scale computational study of the interplay between transcriptional regulation and metabolism , 2007, Molecular systems biology.

[12]  B. Palsson,et al.  Regulation of gene expression in flux balance models of metabolism. , 2001, Journal of theoretical biology.

[13]  B. Palsson,et al.  Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110 , 1994, Applied and environmental microbiology.

[14]  H. Qian,et al.  Energy balance for analysis of complex metabolic networks. , 2002, Biophysical journal.

[15]  Bernhard O. Palsson,et al.  Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets , 2007 .

[16]  Jibin Sun,et al.  Metabolic peculiarities of Aspergillus niger disclosed by comparative metabolic genomics , 2007, Genome Biology.

[17]  Steffen Klamt,et al.  FluxAnalyzer: exploring structure, pathways, and flux distributions in metabolic networks on interactive flux maps , 2003, Bioinform..

[18]  Erwin P. Gianchandani,et al.  Flux balance analysis in the era of metabolomics , 2006, Briefings Bioinform..

[19]  B. Palsson,et al.  Genome-scale Reconstruction of Metabolic Network in Bacillus subtilis Based on High-throughput Phenotyping and Gene Essentiality Data* , 2007, Journal of Biological Chemistry.

[20]  Erwin P. Gianchandani,et al.  Dynamic Analysis of Integrated Signaling, Metabolic, and Regulatory Networks , 2008, PLoS Comput. Biol..

[21]  B. Palsson,et al.  Identifying constraints that govern cell behavior: a key to converting conceptual to computational models in biology? , 2003, Biotechnology and bioengineering.

[22]  B. Palsson,et al.  Towards multidimensional genome annotation , 2006, Nature Reviews Genetics.

[23]  Jong Myoung Park,et al.  Genome-scale analysis of Mannheimia succiniciproducens metabolism. , 2007, Biotechnology and bioengineering.

[24]  Monica L. Mo,et al.  Global reconstruction of the human metabolic network based on genomic and bibliomic data , 2007, Proceedings of the National Academy of Sciences.

[25]  Markus J. Herrgård,et al.  Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model. , 2004, Genome research.

[26]  B. Palsson,et al.  Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. , 2003, Genome research.

[27]  Ronan M. T. Fleming,et al.  Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0 , 2007, Nature Protocols.

[28]  Daniel A Beard,et al.  Extreme pathways and Kirchhoff's second law. , 2002, Biophysical journal.

[29]  F. Doyle,et al.  Dynamic flux balance analysis of diauxic growth in Escherichia coli. , 2002, Biophysical journal.

[30]  G. Church,et al.  Analysis of optimality in natural and perturbed metabolic networks , 2002 .

[31]  Sang Yup Lee,et al.  MetaFluxNet: the management of metabolic reaction information and quantitative metabolic flux analysis , 2003, Bioinform..

[32]  Bernhard O. Palsson,et al.  Matrix Formalism to Describe Functional States of Transcriptional Regulatory Systems , 2006, PLoS Comput. Biol..

[33]  Adam M. Feist,et al.  A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information , 2007, Molecular systems biology.