Skip to main content

Development of an Integrated Framework for Minimal Cut Set Enumeration in Constraint-Based Models

  • Conference paper
  • First Online:

Part of the book series: Advances in Intelligent Systems and Computing ((AISC,volume 477))

Abstract

Under the realm of in silico Metabolic Engineering, pathway analysis approaches to strain optimization have shown a large potential as tools capable of providing an unbiased view over metabolic models. Most of these methods were difficult or impossible to use due to their heavy computational needs, since they are based in the calculation of elementary modes/minimal cut sets in large networks. However, a recent method (MCSEnumerator) has enabled the application of these approaches to genome-scale metabolic models. This work proposes a new software tool where this method is implemented in a novel Java library, that provides support for a plugin for the OptFlux metabolic engineering platform. Together, these tools implement the routines necessary for the calculation of minimal cut sets and their use to provide strain optimization methods. The aim is to provide an open-source software tool that includes an intuitive graphical user interface, thus facilitating its use by the community.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Stephanopoulos, G.: Metabolic Fluxes and Metabolic Engineering 11 (1999)

    Google Scholar 

  2. Patil, K.R., Åkesson, M., Nielsen, J.: Use of genome-scale microbial models for metabolic engineering. Curr. Opin. Biotechnol. 15(1), 64–69 (2004)

    Article  Google Scholar 

  3. Szallasi, Z., Stelling, J., Periwal, V.: System Modeling in Cell Biology (2010)

    Google Scholar 

  4. Varma, A., Palsson, B.O., Arbor, A., Varma, A.: Stoichiometric Flux Balance Models Quantitatively Predict. Appl. Environ. Microbiol. 60(10), 3724–3731 (1994)

    Google Scholar 

  5. Segrè, D., Vitkup, D., Church, G.M.: Analysis of optimality in natural and perturbed metabolic networks. Proc. Natl. Acad. Sci. U. S. A. 99(23), 15112–15117 (2002)

    Article  Google Scholar 

  6. Shlomi, T., Berkman, O., Ruppin, E.: Regulatory on/off minimization of metabolic flux changes after genetic perturbations. Proc. Natl. Acad. Sci. U. S. A. 102(21), 7695–7700 (2005)

    Article  Google Scholar 

  7. Maia, P., Rocha, M., Rocha, I.: In silico constraint-based strain optimization methods: the quest for optimal cell factories. Microbiology and Molecular Biology Reviews 80(1), 45–67 (2016)

    Article  Google Scholar 

  8. Burgard, A.P., Pharkya, P., Maranas, C.D.: Optknock: A bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnol. Bioeng. 84(6), 647–657 (2003)

    Article  Google Scholar 

  9. Patil, K.R., Rocha, I., Förster, J., Nielsen, J.: Evolutionary programming as a platform for in silico metabolic engineering. BMC Bioinformatics 6(1), 308 (2005)

    Google Scholar 

  10. Klamt, S., Gilles, E.D.: Minimal cut sets in biochemical reaction networks. Bioinformatics 20(2), 226–234 (2004)

    Article  Google Scholar 

  11. von Kamp, A., Klamt, S.: Enumeration of Smallest Intervention Strategies in Genome-Scale Metabolic Networks. PLoS Comput. Biol. 10(1), e1003378 (2014)

    Google Scholar 

  12. Schuster, S., Hilgetag, C.: On Elementary Flux Modes in Biochemical Reaction Systems At Steady State. J. Biol. Syst. 02(02), 165–182 (1994)

    Article  Google Scholar 

  13. Hädicke, O., Klamt, S.: Computing complex metabolic intervention strategies using constrained minimal cut sets. Metab. Eng. 13(2), 204–213 (2011)

    Article  Google Scholar 

  14. Ballerstein, K., von Kamp, A., Klamt, S., Haus, U.U.: Minimal cut sets in a metabolic network are elementary modes in a dual network. Bioinformatics 28(3), 381–387 (2012)

    Article  Google Scholar 

  15. de Figueiredo, L.F., Podhorski, A., Rubio, A., Kaleta, C., Beasley, J.E., Schuster, S., Planes, F.J.: Computing the shortest elementary flux modes in genome-scale metabolic networks. Bioinformatics 25(23), 3158–3165 (2009)

    Article  Google Scholar 

  16. Rocha, I., Maia, P., Evangelista, P., Vilaça, P., Soares, S., Pinto, J.P., Nielsen, J., Patil, K.R., Ferreira, E.C., Rocha, M.: OptFlux: an open-source software platform for in silico metabolic engineering. BMC Syst. Biol. 4(1), 45 (2010)

    Article  Google Scholar 

  17. Rocha, M., Maia, P., Mendes, R., Pinto, J.P., Ferreira, E.C., Nielsen, J., Patil, K., Rocha, I.: Natural computation meta-heuristics for the in silico optimization of microbial strains. BMC Bioinformatics 9(1), 499 (2008)

    Google Scholar 

  18. Feist, A.M., Henry, C.S., Reed, J.L., Krummenacker, M., Joyce, A.R., Karp, P.D., Broadbelt, L.J., Hatzimanikatis, V., Palsson, B.Ø.: A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Mol. Syst. Biol. 3(121), 1–18 (2007)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vítor Vieira .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this paper

Cite this paper

Vieira, V., Maia, P., Rocha, I., Rocha, M. (2016). Development of an Integrated Framework for Minimal Cut Set Enumeration in Constraint-Based Models. In: Saberi Mohamad, M., Rocha, M., Fdez-Riverola, F., Domínguez Mayo, F., De Paz, J. (eds) 10th International Conference on Practical Applications of Computational Biology & Bioinformatics. PACBB 2016. Advances in Intelligent Systems and Computing, vol 477. Springer, Cham. https://doi.org/10.1007/978-3-319-40126-3_20

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-40126-3_20

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-40125-6

  • Online ISBN: 978-3-319-40126-3

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics