Skip to main content

Genome-Scale Integrative Data Analysis and Modeling of Dynamic Processes in Yeast

  • Protocol
  • First Online:
Book cover Yeast Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 759))

Abstract

Building a dynamic model of a complete biological cell is one of the great challenges of the 21st century. While this objective could appear unrealistic until recently, considerable improvements in high-throughput data collection techniques, computational performance, data integration, and modeling approaches now allow us to consider it within reach in the near future. In this chapter, we review recent developments that pave the way toward the construction of genome-scale dynamic models. We first describe methodologies for the integration of heterogeneous “omics” datasets, which enable the interpretation of cellular activity at the genome scale and in fluctuating conditions, providing the necessary input to models. We subsequently discuss principles of such models and describe a series of approaches that open perspectives toward the construction of genome-scale dynamic models.

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 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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. Papin, J., Reed, J., and Palsson, B. Ø. (2004) Hierarchical thinking in network biology: the unbiased modularization of biochemical networks. Trends Biochem. Sci. 29, 641–647.

    Article  PubMed  CAS  Google Scholar 

  2. Ghazalpour, A., Doss, S., Sheth, S. S., et al. (2005) Genomic analysis of metabolic pathway gene expression in mice. Genome Biol. 6, R59.

    Article  PubMed  Google Scholar 

  3. Goffard, N., and Weiller, G. (2007) PathExpress: a web-based tool to identify relevant pathways in gene expression data. Nucleic Acids Res. 35, W176–181.

    Article  PubMed  Google Scholar 

  4. Yang, H. H., Hu, Y., Buetow, K. H., and Lee, M. P. (2004) A computational approach to measuring coherence of gene expression in pathways. Genomics 84, 211–217.

    Article  PubMed  CAS  Google Scholar 

  5. Ekins, S., Nikolsky, Y., Bugrim, A., Kirillov, E., and Nikolskaya, T. (2007) Pathway mapping tools for analysis of high content data. Methods Mol. Biol. 356, 319–350.

    PubMed  CAS  Google Scholar 

  6. Kanehisa, M., and Goto, S. (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27–30.

    Article  PubMed  CAS  Google Scholar 

  7. Draghici, S., Khatri, P., Tarca, A. L., et al. (2007) A systems biology approach for pathway level analysis. Genome Res. 17, 1537–1545.

    Article  PubMed  CAS  Google Scholar 

  8. Antonov, A., Dietmann, S., and Mewes, H. (2008) KEGG Spider: interpretation of genomics data in the context of the global gene metabolic network. Genome Biol. 9, R179.

    Article  PubMed  Google Scholar 

  9. Nacher, J. C., Schwartz, J. M., Kanehisa, M., and Akutsu, T. (2006) Identification of metabolic units induced by environmental signals. Bioinformatics 14, e375–383.

    Article  Google Scholar 

  10. Goffard, N., Frickey, T., and Weiller, G. (2009) PathExpress update: the enzyme neighbourhood method of associating gene-expression data with metabolic pathways. Nucleic Acids Res. 37, 335–339.

    Article  Google Scholar 

  11. Schwartz, J. M., Gaugain, C., Nacher, J. C., de Daruvar, A., and Kanehisa, M. (2007) Observing metabolic functions at the genome scale. Genome Biol. 8, R123.

    Article  PubMed  Google Scholar 

  12. Papin, J. A., Price, N. D., Wiback, S. J., Fell, D. A., and Palsson, B. Ø. (2003) Metabolic pathways in the post-genome era. Trends Biochem. Sci. 28, 250–258.

    Article  PubMed  CAS  Google Scholar 

  13. Schilling, C. H., Letscher, D., and Palsson, B. Ø. (2000) Theory for the systemic definition of metabolic pathways and their use in interpreting metabolic function from a pathway-oriented perspective. J. Theor. Biol. 203, 229–248.

    Article  PubMed  CAS  Google Scholar 

  14. Schuster, S., Fell, D. A., and Dandekar, T. (2000) A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nat. Biotechnol. 18, 326–332.

    Article  PubMed  CAS  Google Scholar 

  15. Barriot, R., Poix, J., Groppi, A., et al. (2004) New strategy for the representation and the integration of biomolecular knowledge at a cellular scale. Nucleic Acids Res. 32, 3581–3589.

    Article  PubMed  CAS  Google Scholar 

  16. Vido, K., Spector, D., Lagniel, G., et al. (2001) A proteome analysis of the cadmium response in Saccharomyces cerevisiae. J. Biol. Chem. 276, 8469–8474.

    Article  PubMed  CAS  Google Scholar 

  17. Castrillo, J. I., Zeef, L. A., Hoyle, D. C., et al. (2007) Growth control of the eukaryote cell: a systems biology study in yeast. J. Biol. 6, 4.

    Article  PubMed  Google Scholar 

  18. Ishii, N., Nakahigashi, K., Baba, T., et al. (2007) Multiple high-throughput analyses monitor the response of E. coli to perturbations. Science 316, 593–597.

    Article  PubMed  CAS  Google Scholar 

  19. Beyer, A., Hollunder, J., Nasheuer, H. P., and Wilhelm, T. (2004) Post-transcriptional expression regulation in the yeast Saccharomyces cerevisiae on a genomic scale. Mol. Cell. Proteomics 3, 1083–1092.

    Article  PubMed  CAS  Google Scholar 

  20. Bradley, P. H., Brauer, M. J., Rabinowitz, J. D., and Troyanskaya, O. G. (2009) Coordinated concentration changes of transcripts and metabolites in Saccharomyces cerevisiae. PLoS Comput. Biol. 5, e1000270.

    Article  PubMed  Google Scholar 

  21. Yeang, C. H., and Vingron, M. (2006) A joint model of regulatory and metabolic networks. BMC Bioinformatics 7, 332.

    Article  PubMed  Google Scholar 

  22. Sontag, E., Kiyatkin, A., and Kholodenko, B. N. (2004) Inferring dynamic architecture of cellular networks using time series of gene expression, protein and metabolite data. Bioinformatics 20, 1877–1886.

    Article  PubMed  CAS  Google Scholar 

  23. Grimbs, S., Selbig, J., Bulik, S., Holzhütter, H. G., and Steuer, R. (2007) The stability and robustness of metabolic states: identifying stabilizing sites in metabolic networks. Mol. Syst. Biol. 3, 146.

    Article  PubMed  Google Scholar 

  24. Conradi, C., Flockerzi, D., Raisch, J., and Stelling, J. (2007) Subnetwork analysis reveals dynamic features of complex (bio)chemical networks. Proc. Natl. Acad. Sci. USA 104, 19175–19180.

    Article  PubMed  Google Scholar 

  25. Whelan, K. E., and King, R. D. (2008) Using a logical model to predict the growth of yeast. BMC Bioinformatics 9, 97.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  27. Klamt, S., Saez-Rodriguez, J., Lindquist, J. A., Simeoni, L., and Gilles, E. D. (2006) A methodology for the structural and functional analysis of signaling and regulatory networks. BMC Bioinformatics 7, 56.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  29. Saez-Rodriguez, J., Simeoni, L., Lindquist, J. A., et al. (2007) A logical model provides insights into T cell receptor signaling. PLoS Comput. Biol. 3, e163.

    Article  PubMed  Google Scholar 

  30. Gianchandani, E. P., Joyce, A. R., Palsson, B. Ø., and Papin, J. A. (2009) Functional states of the genome-scale Escherichia coli transcriptional regulatory system. PLoS Comput. Biol. 5, e1000403.

    Article  PubMed  Google Scholar 

  31. Schwartz, J. M., and Kanehisa, M. (2006) Quantitative elementary mode analysis of metabolic pathways: the example of yeast glycolysis. BMC Bioinformatics 7, 186.

    Article  PubMed  Google Scholar 

  32. Varma, A., and Palsson, B. Ø. (1994) Metabolic flux balancing: basic concepts, scientific and practical use. Bio/Technology 12, 994–998.

    Article  CAS  Google Scholar 

  33. 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.

    Article  PubMed  Google Scholar 

  34. Steuer, R., Gross, T., Selbig, J., and Blasius, B. (2006) Structural kinetic modeling of metabolic networks. Proc. Natl. Acad. Sci. USA 103, 11868–11873.

    Article  PubMed  CAS  Google Scholar 

  35. Smallbone, K., Simeonidis, E., Broomhead, D. S., and Kell, D. B. (2007) Something from nothing – bridging the gap between constraint-based and kinetic modelling. FEBS J. 274, 5576–5585.

    Article  PubMed  CAS  Google Scholar 

  36. Teusink, B., Passarge, J., Reijenga, C. A., et al. (2000) Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry. Eur. J. Biochem. 267, 5313–5329.

    Article  PubMed  CAS  Google Scholar 

  37. Ao, P., Lee, L., Lidstrom, M., Yin, L., and Zhu, X. (2008) Towards kinetic modeling of global metabolic networks: Methylobacterium extorquens AM1 growth as validation. Chin. J. Biotechnol. 24, 980–994.

    Article  CAS  Google Scholar 

  38. Ederer, M., and Gilles, E. D. (2007) Thermodynamically feasible kinetic models of reaction networks. Biophys. J. 92, 1846–1857.

    Article  PubMed  CAS  Google Scholar 

  39. Qian, H., and Beard, D. A. (2005) Thermodynamics of stoichiometric biochemical networks in living systems far from equilibrium. Biophys. Chem. 114, 213–220.

    Article  PubMed  CAS  Google Scholar 

  40. Hoppe, A., Hoffmann, S., and Holzhütter, H. G. (2007) Including metabolite concentrations into flux balance analysis: thermodynamic realizability as a constraint on flux distributions in metabolic networks. BMC Syst. Biol. 1, 23.

    Article  PubMed  Google Scholar 

  41. Henry, C. S., Broadbelt, L. J., and Hatzimanikatis, V. (2007) Thermodynamics-based metabolic flux analysis. Biophys. J. 92, 1792–1805.

    Article  PubMed  CAS  Google Scholar 

  42. Jamshidi, N., and Palsson, B. Ø. (2008) Formulating genome-scale kinetic models in the post-genome era. Mol. Syst. Biol. 4, 171.

    Article  PubMed  Google Scholar 

  43. Gutenkunst, R. N., Waterfall, J. J., Casey, F. P., Brown, K. S., Myers, C. R., and Sethna, J. P. (2007) Universally sloppy parameter sensitivities in systems biology models. PLoS Comput. Biol. 3, 1871–1878.

    Article  PubMed  CAS  Google Scholar 

  44. Daniels, B. C., Chen, Y. J., Sethna, J. P., Gutenkunst, R. N., and Myers, C. R. (2008) Sloppiness, robustness, and evolvability in systems biology. Curr. Opin. Biotechnol. 19, 389–395.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jean-Marc Schwartz .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Humana Press

About this protocol

Cite this protocol

Schwartz, JM., Gaugain, C. (2011). Genome-Scale Integrative Data Analysis and Modeling of Dynamic Processes in Yeast. In: Castrillo, J., Oliver, S. (eds) Yeast Systems Biology. Methods in Molecular Biology, vol 759. Humana Press. https://doi.org/10.1007/978-1-61779-173-4_24

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-173-4_24

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-172-7

  • Online ISBN: 978-1-61779-173-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics