Logical Modelling of Gene Regulatory Networks with GINsim

  • Claudine ChaouiyaEmail author
  • Aurélien Naldi
  • Denis Thieffry
Part of the Methods in Molecular Biology book series (MIMB, volume 804)


Discrete mathematical formalisms are well adapted to model large biological networks, for which detailed kinetic data are scarce. This chapter introduces the reader to a well-established qualitative (logical) framework for the modelling of regulatory networks. Relying on GINsim, a software implementing this logical formalism, we guide the reader step by step towards the definition and the analysis of a simple model of the lysis–lysogeny decision in the bacteriophage λ.

Key words

Networks Logical modelling Qualitative analysis Graph Regulatory circuit Dynamical simulation 



A.N. has been supported by a PhD grant from the French Ministry of Research and Technology. This project was further supported by research grants from the EU FP6 (DIAMONDS STREP) and FP7 (APOSYS large scale project) programs, and by the Belgian Science Policy Office (IAP BioMaGNet).


  1. 1.
    Thieffry D, Thomas R. (1995) Dynamical behaviour of biological regulatory networks, II. Immunity control in bacteriophage lambda. Bull Math Biol, 57(2):277–297.Google Scholar
  2. 2.
    Filopon D, Mérieau A, Bernot G, Comet JP, LeBerre R, Guery B, Polack B, Guespin-Michel J. (2006) Epigenetic acquisition of inducibility of type III cytotoxicity in aeruginosa. BMC Bioinformatics 2006, 7:272.Google Scholar
  3. 3.
    Simão E, Remy E, Thieffry D, Chaouiya C. (2005) Qualitative modelling of regulated metabolic pathways: application to the tryptophan biosynthesis in E. coli. Bioinformatics, 21(Suppl 2):190–196.Google Scholar
  4. 4.
    Chaves M, Albert R, Sontag ED. (2005) Robustness and fragility of Boolean models for genetic regulatory networks. J Theor Biol, 235(3):431–449.PubMedCrossRefGoogle Scholar
  5. 5.
    Sánchez L, Chaouiya C, Thieffry D. (2008) Segmenting the fly embryo: a logical analysis of the segment polarity cross-regulatory module. Int J Dev Biol, 52(8):1059–1075.PubMedCrossRefGoogle Scholar
  6. 6.
    González A, Chaouiya C, Thieffry D. (2008) Logical modelling of the role of the Hh pathway in the patterning of the Drosophila wing disc. Bioinformatics, 24:i234–i240.PubMedCrossRefGoogle Scholar
  7. 7.
    Fauré A, Naldi A, Lopez F, Chaouiya C, Ciliberto A, Thieffry D. (2009) Modular logical modelling of the budding yeast cell cycle. Mol Biosyst, 5:1787–1796.PubMedCrossRefGoogle Scholar
  8. 8.
    Irons DJ. (2009) Logical analysis of the budding yeast cell cycle. J Theor Biol, 257(4): 543–559.PubMedCrossRefGoogle Scholar
  9. 9.
    Mendoza L. (2006) A network model for the control of the differentiation process in Th cells. Biosystems, 84(2):101–114.PubMedCrossRefGoogle Scholar
  10. 10.
    Ptashne M. (2004) A Genetic Switch: Phage Lambda Revisited. 3rd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.Google Scholar
  11. 11.
    Ackers GK, Johnson AD, Shea MA. (1982) Quantitative model for gene regulation by lambda phage repressor. Proc Natl Acad Sci U S A, 79(4):1129–1133.PubMedCrossRefGoogle Scholar
  12. 12.
    Arkin A, Ross J, McAdams HH. (1998) Stochastic kinetic analysis of a developmental pathway bifurcation in phage lambda-infected Escherichia coli cells. Genetics, 149:1633–1648.PubMedGoogle Scholar
  13. 13.
    Matsuno H, Doi A, Nagasaki M, Miyano S. (2000) Hybrid Petri net representation of gene regulatory network. In Pac Symp Biocomput 2000:341–352.Google Scholar
  14. 14.
    Naldi A, Berenguier D, Fauré A, Lopez F, Thieffry D, Chaouiya C. (2009) Logical modelling of regulatory networks with GINsim 2.3. Biosystems, 97(2):134–139.Google Scholar
  15. 15.
    Naldi A, Thieffry D, Chaouiya C. (2007) Decision diagrams for the representation of logical models of regulatory networks. Lect Notes Comput Sci, 4695:233–247.CrossRefGoogle Scholar
  16. 16.
    Naldi A, Remy E, Thieffry D, Chaouiya C. (2009) A reduction of logical regulatory graphs preserving essential dynamical properties. Lect Notes Comput Sci, 5688:266–280.CrossRefGoogle Scholar
  17. 17.
    Hartwell L, Hopfield J, Leibler S, Murray A. (1999) From molecular to modular cell biology. Nature, 402:C47–C52.PubMedCrossRefGoogle Scholar
  18. 18.
    Mirschel S, Steinmetz K, Rempel M, Ginkel M, Gilles ED. (2009) ProMoT: modular modeling for systems biology. Bioinformatics, 25(5):687–689.PubMedCrossRefGoogle Scholar
  19. 19.
    Fauré A, Naldi A, Chaouiya C, Thieffry D. (2006) Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycle. Bioinformatics, 22(14):124–131.CrossRefGoogle Scholar
  20. 20.
    Thieffry D. (2007) Dynamical roles of biological regulatory circuits. Brief Bioinformatics, 8(4):220–225.PubMedCrossRefGoogle Scholar
  21. 21.
    Remy E, Ruet P. (2008) From minimal signed circuits to the dynamics of Boolean regulatory networks. Bioinformatics, 24(16):i220–i226.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Claudine Chaouiya
    • 1
    Email author
  • Aurélien Naldi
    • 2
  • Denis Thieffry
    • 3
  1. 1.Instituto Gulbenkian de CiênciaOeirasPortugal
  2. 2.TAGC, INSERM U928MarseilleFrance
  3. 3.Institut de Biologie de l’Ecole Normale Supérieure (IBENS), UMR ENS, CNRS 8197, INSERM 1024ParisFrance

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