Skip to main content

Flux Balance Analysis: Interrogating Genome-Scale Metabolic Networks

  • Protocol
  • First Online:
Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 500))

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sun, J., Lu, X., Rinas, U., and Zeng, A. P. (2007) Metabolic peculiarities of Aspergillus niger disclosed by comparative metabolic genomics. Genome Biol. 8, R182.

    Article  PubMed  Google Scholar 

  2. Heinemann, M., Kummel, A., Ruinatscha, R. and Panke, S. (2005) In silico genome-scale reconstruction and validation of the Staphylococcus aureus metabolic network. Biotechnol. Bioeng. 92, 850–864.

    Article  PubMed  CAS  Google Scholar 

  3. Duarte, N. C., Herrgard, M. J., and Palsson, B. O. (2004) Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model. Genome Res. 14, 1298–1309.

    Article  PubMed  CAS  Google Scholar 

  4. Duarte, N. C., Becker, S. A., Jamshidi, N., Thiele, I., Mo, M. L., Vo, T. D., Srivas, R., and Palsson, B. O. (2007) Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc. Natl. Acad. Sci. USA 104, 1777–1782.

    Article  PubMed  CAS  Google Scholar 

  5. Feist, A. M., Henry, C. S., Reed, J. L., Krummenacker, M., Joyce, A. R., Karp, P. D., Broadbelt, L. J., Hatzimanikatis, V., and Palsson, B. O. (2007) A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Mol. Syst. Biol. 3, 121.

    Article  PubMed  Google Scholar 

  6. Stelling, J., Klamt, S., Bettenbrock, K., Schuster, S., and Gilles, E. D. (2002) Metabolic network structure determines key aspects of functionality and regulation. Nature 420, 190–193.

    Article  PubMed  CAS  Google Scholar 

  7. Kauffman, K. J., Prakash, P., and Edwards, J. S. (2003) Advances in flux balance analysis. Curr. Opin. Biotechnol. 14, 491–496.

    Article  PubMed  CAS  Google Scholar 

  8. Lee, J. M., Gianchandani, E. P., and Papin, J. A. (2006) Flux balance analysis in the era of metabolomics. Brief. Bioinform. 7, 140–150.

    Article  PubMed  Google Scholar 

  9. Covert, M. W., Famili, I., and Palsson, B. O. (2003) Identifying constraints that govern cell behavior: a key to converting conceptual to computational models in biology? Biotechnol. Bioeng. 84, 763–772.

    Article  PubMed  CAS  Google Scholar 

  10. Mahadevan, R., Edwards, J. S., and Doyle, F. J. 3rd (2002) Dynamic flux balance analysis of diauxic growth in Escherichia coli. Biophys. J. 83, 1331–1340.

    Article  PubMed  CAS  Google Scholar 

  11. Varma, A. and Palsson, B. O. (1994) Stoichiometric flux balance models quantitatively predict growth and metabolic by-product secretion in wild-type Escherichia coli W3110. Appl. Environ. Microbiol. 60, 3724–3731.

    PubMed  CAS  Google Scholar 

  12. Beard, D. A., Liang, S. D., and Qian, H. (2002) Energy balance for analysis of complex metabolic networks. Biophys. J. 83, 79–86.

    Article  PubMed  CAS  Google Scholar 

  13. Covert, M. W., Schilling, C. H., and Palsson, B. (2001) Regulation of gene expression in flux balance models of metabolism. J. Theor. Biol. 213, 73–88.

    Article  PubMed  CAS  Google Scholar 

  14. Herrgard, M. J., Lee, B. S., Portnoy, V., and Palsson, B. O. (2006) Integrated analysis of regulatory and metabolic networks reveals novel regulatory mechanisms in Saccharomyces cerevisiae. Genome Res. 16, 627–635.

    Article  PubMed  CAS  Google Scholar 

  15. Gianchandani, E. P., Papin, J. A., Price, N. D., Joyce, A. R., and Palsson, B. O. (2006) Matrix formalism to describe functional states of transcriptional regulatory systems. PLoS Comput. Biol. 2, e101.

    Article  PubMed  Google Scholar 

  16. Shlomi, T., Eisenberg, Y., Sharan, R., and Ruppin, E. (2007) A genome-scale computational study of the interplay between transcriptional regulation and metabolism. Mol. Syst. Biol. 3, 101.

    Article  PubMed  Google Scholar 

  17. Lee, J. M., Gianchandani, E. P., Eddy, J. A., and Papin, J. A. (2008) Dynamic analysis of integrated signaling, metabolic, and regulatory networks. PLoS Comput. Biol. 4, e1000086.

    Google Scholar 

  18. Segre, D., Vitkup, D., and Church, G. M. (2002) Analysis of optimality in natural and perturbed metabolic networks. Proc. Natl. Acad. Sci. USA 99, 15112–15117.

    Article  PubMed  CAS  Google Scholar 

  19. Jamshidi, N. and Palsson, B. O. (2007) Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets. BMC Syst. Biol. 1, 26.

    Article  PubMed  Google Scholar 

  20. Thiele, I., Vo, T. D., Price, N. D., and Palsson, B. O. (2005) Expanded metabolic reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an in silico genome-scale characterization of single- and double-deletion mutants. J. Bacteriol. 187, 5818–5830.

    Article  PubMed  CAS  Google Scholar 

  21. Oh, Y. K., Palsson, B. O., Park, S. M., Schilling, C. H., and Mahadevan, R. (2007) Genome-scale reconstruction of metabolic network in Bacillus subtilis based on high-throughput phenotyping and gene essentiality data. J. Biol. Chem. 282, 28791–28799.

    Article  PubMed  CAS  Google Scholar 

  22. Kim, T. Y., Kim, H. U., Park, J. M., Song, H., Kim, J. S., and Lee, S. Y. (2007) Genome-scale analysis of Mannheimia succiniciproducens metabolism. Biotechnol. Bioeng. 97, 657–671.

    Article  PubMed  CAS  Google Scholar 

  23. Francke, C., Siezen, R. J., and Teusink, B. (2005) Reconstructing the metabolic network of a bacterium from its genome. Trends Microbiol. 13, 550–558.

    Article  PubMed  CAS  Google Scholar 

  24. Reed, J. L., Famili, I., Thiele, I., and Palsson, B. O. (2006) Towards multidimensional genome annotation. Nat. Rev. Genet. 7, 130–141.

    Article  PubMed  CAS  Google Scholar 

  25. Becker, S. A., Feist, A. M., Mo, M. L., Hannum, G., Palsson, B. O., and Herrgard, M. J. (2007) Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox. Nat. Protoc. 2, 727–738.

    Article  PubMed  CAS  Google Scholar 

  26. Klamt, S., Stelling, J., Ginkel, M., and Gilles, E. D. (2003) FluxAnalyzer: exploring structure, pathways, and flux distributions in metabolic networks on interactive flux maps. Bioinformatics 19, 261–269.

    Article  PubMed  CAS  Google Scholar 

  27. Zhu, T., Phalakornkule, C., Ghosh, S., Grossmann, I. E., Koepsel, R. R., Ataai, M. M., and Domach, M. M. (2003) A metabolic network analysis & NMR experiment design tool with user interface-driven model construction for depth-first search analysis. Metab. Eng. 5, 74–85.

    Article  PubMed  CAS  Google Scholar 

  28. Urbanczik, R. (2006) SNA–a toolbox for the stoichiometric analysis of metabolic networks. BMC Bioinformatics 7, 129.

    Article  PubMed  Google Scholar 

  29. Lee, D. Y., Yun, H., Park, S., and Lee, S. Y. (2003) MetaFluxNet: the management of metabolic reaction information and quantitative metabolic flux analysis. Bioinformatics 19, 2144–2146.

    Article  PubMed  CAS  Google Scholar 

  30. Mahadevan, R. and Schilling, C. H. (2003) The effects of alternate optimal solutions in constraint-based genome-scale metabolic models. Metab. Eng. 5, 264–276.

    Article  PubMed  CAS  Google Scholar 

  31. Forster, J., Famili, I., Fu, P., Palsson, B. O., and Nielsen, J. (2003) Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. Genome Res. 13, 244–253.

    Article  PubMed  CAS  Google Scholar 

  32. Price, N. D., Famili, I., Beard, D. A., and Palsson, B. O. (2002) Extreme pathways and Kirchhoff's second law. Biophys. J. 83, 2879–2882.

    Article  PubMed  CAS  Google Scholar 

  33. Varma, A. and Palsson, B. O. (1993) Metabolic capabilities of Escherichia coli. 2. Optimal-growth patterns. J. Theor. Biol. 165, 503–522.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to thank the National Science Foundation CAREER program (grant# 0643548 to JP) for financial support. MAO and AKC contributed equally to this work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jason A. Papin .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press

About this protocol

Cite this protocol

Oberhardt, M., Chavali, A., Papin, J. (2009). Flux Balance Analysis: Interrogating Genome-Scale Metabolic Networks. In: Maly, I. (eds) Systems Biology. Methods in Molecular Biology, vol 500. Humana Press. https://doi.org/10.1007/978-1-59745-525-1_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-525-1_3

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-64-0

  • Online ISBN: 978-1-59745-525-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics