Skip to main content
SpringerLink
Log in

Formal Analysis of Gene Networks Using Network Motifs

  • Conference paper
  • First Online:
Biomedical Engineering Systems and Technologies (BIOSTEC 2013)

Part of the book series: Communications in Computer and Information Science ((CCIS,volume 452))

Abstract

We developed a theoretical framework to analyse gene regulatory networks. Our framework is based on the formal methods which are well-known techniques to analyse software/hardware systems. Behaviours of gene networks are abstracted into transition systems which has discrete time structure. We characterise possible behaviours of given networks by linear temporal logic (LTL) formulae. By checking the satisfiability of LTL formulae, we analyse whether all/some behaviours of given networks satisfy given biological properties. Due to the complexity of LTL satisfiability checking, analyses of large networks are generally intractable in this method. To mitigate this computational difficulty, we proposed approximate analysis method using network motifs to circumvent the computational difficulty of LTL satisfiability checking. Experiments show that our approximate method is surprisingly efficient.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
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

Institutional subscriptions

Notes

  1. 1.

    Note that the symbol \(x_y\) is used for both the threshold and proposition but we can clearly distinguish them from the context.

  2. 2.

    This contrasts with the framework in which behaviours are described in ordinary differential equations.

  3. 3.

    http://arabidopsis.med.ohio-state.edu/REIN/

  4. 4.

    The following computational environment was used: openSUSE 11.0, Intel(R) Pentium(R) D CPU 3.00 GHz and 2 GB of RAM.

References

  1. Ito, S., Izumi, N., Hagihara, S., Yonezaki, N.: Qualitative analysis of gene regulatory networks by satisfiability checking of linear temporal logic. In: 10th IEEE International Conference on Bioinformatics & Bioengineering, pp. 232–237. IEEE Computer Society (2010)

    Google Scholar 

  2. Pnueli, A., Rosner, R.: On the synthesis of a reactive module. In: 16th ACM SIGPLAN-SIGACT Symposium on Principles of Programming Languages, pp. 179–190. ACM Press (1989)

    Google Scholar 

  3. Abadi, M., Lamport, L., Wolper, P.: Realizable and unrealizable specifications of reactive systems. In: Ausiello, G., Dezani-Ciancaglini, M., Rocca, S.R.D. (eds.) Automata, Languages and Programming. LNCS, vol. 372, pp. 1–17. Springer, Heidelberg (1989)

    Chapter  Google Scholar 

  4. Mori, R., Yonezaki, N.: Several realizability concepts in reactive objects. In: Information Modeling and Knowledge Bases IV, pp. 407–424 (1993)

    Google Scholar 

  5. Sistla, A.P., Clarke, E.M.: The complexity of propositional linear temporal logics. J. ACM 32, 733–749 (1985)

    Article  MathSciNet  MATH  Google Scholar 

  6. Alon, U.: Network motifs: theory and experimental approaches. Nat. Rev. Genet. 8, 450–461 (2007)

    Article  Google Scholar 

  7. Thomas, R., Kauffman, M.: Multistationarity, the basis of cell differentiation and memory. II. logical analysis of regulatory networks in terms of feedback circuits. Chaos 11, 180–195 (2001)

    Article  MathSciNet  MATH  Google Scholar 

  8. Snoussi, E., Thomas, R.: Logical identification of all steady states: the concept of feedback loop characteristic states. Bull. Math. Biol. 55, 973–991 (1993)

    Article  MATH  Google Scholar 

  9. Farwer, B.: \(\omega \)-Automata. In: Grädel, E., Thomas, W., Wilke, T. (eds.) Automata Logics, and Infinite Games: A Guide to Current Research, pp. 3–20. Springer-Verlag New York, Inc., New York (2002)

    Chapter  Google Scholar 

  10. Vardi, M.Y., Wolper, P.: Reasoning about infinite computations. Inf. Comput. 115, 1–37 (1994)

    Article  MathSciNet  MATH  Google Scholar 

  11. Aoshima, T., Sakuma, K., Yonezaki, N.: An efficient verification procedure supporting evolution of reactive system specifications. In: 4th International Workshop on Principles of Software Evolution, pp. 182–185. ACM, New York (2001)

    Google Scholar 

  12. Ito, S., Ichinose, T., Shimakawa, M., Izumi, N., Hagihara, S., Yonezaki, N.: Modular analysis of gene networks by linear temporal logic. J. Integr. Bioinform. 10, 216 (2013)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Fisheries University, Shimonoseki, Japan

    Sohei Ito

  2. Tokyo Institute of Technology, Tokyo, Japan

    Takuma Ichinose, Masaya Shimakawa, Shigeki Hagihara & Naoki Yonezaki

  3. Jumonji University, Niiza, Japan

    Naoko Izumi

Authors
  1. Sohei Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takuma Ichinose
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masaya Shimakawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naoko Izumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shigeki Hagihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naoki Yonezaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sohei Ito .

Editor information

Editors and Affiliations

  1. Universitat Politècnica de Catalunya, Barcelona, Spain

    Mireya Fernández-Chimeno

  2. Instituto Gulbenkian de Ciência, Oeiras, Portugal

    Pedro L. Fernandes

  3. Boston College, Chestnut Hill, Massachusetts, USA

    Sergio Alvarez

  4. University of Guelph, Guelph, Canada

    Deborah Stacey

  5. University of Vic, Vic, Spain

    Jordi Solé-Casals

  6. Technical University of Lisbon, Lisbon, Portugal

    Ana Fred

  7. New University of Lisbon, Lisboa, Portugal

    Hugo Gamboa

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Ito, S., Ichinose, T., Shimakawa, M., Izumi, N., Hagihara, S., Yonezaki, N. (2014). Formal Analysis of Gene Networks Using Network Motifs. In: Fernández-Chimeno, M., et al. Biomedical Engineering Systems and Technologies. BIOSTEC 2013. Communications in Computer and Information Science, vol 452. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44485-6_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-44485-6_10

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-44484-9

  • Online ISBN: 978-3-662-44485-6

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics

Search

Navigation