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A Domain Specific Language Approach for Genetic Regulatory Mechanisms Analysis

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Part of the Lecture Notes in Computer Science book series (TOPNOC,volume 7400)

Abstract

Systems biology and synthetic biology can be considered as model-driven methodologies. In this context, models are used to discover emergent properties arising from the complex interactions between components. Most available tools propose simulation frameworks to study models of biological systems. Simulation only explores a limited number of behaviors of these models. This may lead to a biased view of the system. On the contrary, model checking explores all the possible behaviors. The use of model checking in the domain of life sciences is limited. It suffers from the complexity of modeling languages designed by and for computer scientists. This article describes an approach based on Domain Specific Languages. It provides a comprehensible, yet formal, language called GReg to describe genetic regulatory mechanisms and their properties, and to apply powerful model checking techniques on them. GReg’s objective is to shelter the user from the complexity of those underlying techniques.

Keywords

  • Model Check
  • Synthetic Biology
  • System Biology Markup Language
  • Concrete Syntax
  • Genetic Regulatory Network

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Besson, B., de Jong, H., Monteiro, P., Page, M.: GNA, http://ibis.inrialpes.fr/article122.html

  2. Buchs, D., Guelfi, N.: A Formal Specification Framework for Object-Oriented Distributed Systems. IEEE Transactions on Software Engineering 26(7), 635–652 (2000)

    CrossRef  Google Scholar 

  3. Buchs, D., Hostettler, S.: Sigma Decision Diagrams. In: TERMGRAPH 2009: 5th International Workshop on Computing with Terms and Graphs, pp. 18–32. No. TR-09-05, Università di Pisa (2009)

    Google Scholar 

  4. Buchs, D., Hostettler, S., Marechal, A., Risoldi, M.: AlPiNA: A Symbolic Model Checker. In: Lilius, J., Penczek, W. (eds.) PETRI NETS 2010. LNCS, vol. 6128, pp. 287–296. Springer, Heidelberg (2010)

    CrossRef  Google Scholar 

  5. Buchs, D., Hostettler, S., Marechal, A., Risoldi, M.: AlPiNA: An Algebraic Petri Net Analyzer. In: Esparza, J., Majumdar, R. (eds.) TACAS 2010. LNCS, vol. 6015, pp. 349–352. Springer, Heidelberg (2010)

    CrossRef  Google Scholar 

  6. Burch, J., Clarke, E., McMillan, K., Dill, D., Hwang, L.: Symbolic Model Checking: 1020 States and Beyond. Information and Computation 98 (1992)

    Google Scholar 

  7. Chabrier, N., Chiaverini, M., Danos, V., Fages, F., Schachter, V.: Modeling and Querying Biomolecular Interaction Networks. Theoretical Computer Science 325(1), 25–44 (2004)

    MathSciNet  MATH  CrossRef  Google Scholar 

  8. Chaouiya, C., Klaudel, H., Pommereau, F.: A Modular, Qualitative Modeling of Regulatory Networks Using Petri Nets. In: Modeling in Systems Biology, Computational Biology, vol. 16, pp. 253–279. Springer (2011)

    Google Scholar 

  9. Chaouiya, C., Remy, E., Mossé, B., Thieffry, D.: Qualitative Analysis of Regulatory Graphs: A Computational Tool Based on a Discrete Formal Framework. In: Benvenuti, L., De Santis, A., Farina, L. (eds.) Positive Systems. LNCIS, vol. 294, pp. 119–126. Springer, Heidelberg (2003)

    CrossRef  Google Scholar 

  10. Eclipse Foundation: Eclipse Modeling Project, http://www.eclipse.org/modeling

  11. Clarke, E.M., Grumberg, O., Peled, D.A.: Model checking. MIT Press, Cambridge (1999)

    Google Scholar 

  12. EPI Contraintes, INRIA Paris-Rocquencourt: BioCham, http://contraintes.inria.fr/BioCham/

  13. Fowler, M.: Domain-Specific Languages. Addison-Wesley Professional (2010)

    Google Scholar 

  14. Hucka, M., Bergmann, F., Hoops, S., Keating, S., Sahle, S., Schaff, J., Smith, L., Wilkinson, B.: The Systems Biology Markup Language (SBML): Language Specification for Level 3 Version 1 Core (2010), available from Nature Precedings

    Google Scholar 

  15. Jacob, F., Monod, J.: Genetic Regulatory Mechanisms in the Synthesis of Proteins. Journal of Molecular Biology 3, 318–356 (1961)

    CrossRef  Google Scholar 

  16. Jensen, K., Kristensen, L., Wells, L.: Coloured Petri Nets and CPN Tools for modelling and validation of concurrent systems. International Journal on Software Tools for Technology Transfer (STTT) 9, 213–254 (2007)

    Google Scholar 

  17. Jong, H.D.: Modeling and simulation of genetic regulatory systems: a literature review. Journal of Computational Biology 9(1), 69–105 (2002)

    Google Scholar 

  18. Jong, H.D., Geiselmann, J., Hernandez, C., Page, M.: Genetic Network Analyzer: qualitative simulation of genetic regulatory networks. Bioinformatics 19(3), 336–344 (2003)

    CrossRef  Google Scholar 

  19. Pedro, L.: A Systematic Language Engineering Approach for Prototyping Domain Specific Languages. Ph.D. thesis, Université de Genève (2009), thesis # 4068

    Google Scholar 

  20. Longabaugh, W., Davidson, E., Bolouri, H.: Visualization, documentation, analysis, and communication of large-scale gene regulatory networks. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 1789(4), 363–374 (2009)

    CrossRef  Google Scholar 

  21. Monteiro, P.T., Ropers, D., Mateescu, R., Freitas, A.T., de Jong, H.: Temporal Logic Patterns for Querying Qualitative Models of Genetic Regulatory Networks. Bioinformatics 24(16), i227–i233 (2008)

    Google Scholar 

  22. Moodie, S., Novere, N.L., Demir, E., Mi, H., Villeger, A.: Systems Biology Graphical Notation: Process Description language Level 1 (2011), available from Nature Precedings, http://dx.doi.org/10.1038/npre.2011.3721.4

  23. Nagasaki, M., Doi, A., Matsuno, H., Miyano, S.: A Versatile Petri Net Based Architecture for Modeling and Simulation of Complex Biological Processes. Genome Informatics 15(1), 180–197 (2004)

    Google Scholar 

  24. Naldi, A., Berenguier, D., Fauré, A., Lopez, F., Thieffry, D., Chaouiya, C.: Logical Modelling of Regulatory Networks with GINsim 2.3. Biosystems 97(2) (2009)

    Google Scholar 

  25. Naldi, A., Chaouiya, C., Thieffry, D.: GINsim, http://gin.univ-mrs.fr/

  26. Pedersen, M., Plotkin, G.D.: A Language for Biochemical Systems: Design and Formal Specification. In: Priami, C., Breitling, R., Gilbert, D., Heiner, M., Uhrmacher, A.M. (eds.) Transactions on Computational Systems Biology XII. LNCS, vol. 5945, pp. 77–145. Springer, Heidelberg (2010)

    CrossRef  Google Scholar 

  27. Reisig, W.: Petri nets. An Introduction. EATCS Monographs on Theoretical Compute Science, vol. 4. Springer (1985)

    Google Scholar 

  28. Rohr, C., Marwan, W., Heiner, M.: Snoopy - a unifying Petri net framework to investigate biomolecular networks. Bioinformatics 26(7), 974–975 (2010)

    CrossRef  Google Scholar 

  29. Sedlmajer, N.: GReg: a domain specific language for the modeling of genetic regulatory mechanisms. Master’s thesis, University of Geneva (2012), https://smv.unige.ch/student-projects/finished-projects/files/sedlmajer/

  30. Institute for Systems Biology and the Davidson Lab at Caltech: BioTapestry, http://www.BioTapestry.org/

  31. Brandenburg University of Technology: Snoopy, http://www-dssz.informatik.tu-cottbus.de/DSSZ/Software/Snoopy

  32. The University of Tokyo: Cell Illustrator, http://www.cellillustrator.com/

  33. Thomas, R.: Regulatory Networks seen as Asynchronous Automata: a Logical Description. Journal of Theoretical Biology 153, 1–23 (1991)

    CrossRef  Google Scholar 

  34. Valmari, A.: The State Explosion Problem. In: Reisig, W., Rozenberg, G. (eds.) APN 1998. LNCS, vol. 1491, pp. 429–528. Springer, Heidelberg (1998)

    CrossRef  Google Scholar 

  35. Vautherin, J.: Parallel Systems Specifications with Coloured Petri Nets and Algebraic Specifications. In: Rozenberg, G. (ed.) APN 1987. LNCS, vol. 266, pp. 293–308. Springer, Heidelberg (1987)

    CrossRef  Google Scholar 

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Sedlmajer, N., Buchs, D., Hostettler, S., Linard, A., López Bóbeda, E., Marechal, A. (2012). A Domain Specific Language Approach for Genetic Regulatory Mechanisms Analysis. In: Jensen, K., van der Aalst, W.M., Ajmone Marsan, M., Franceschinis, G., Kleijn, J., Kristensen, L.M. (eds) Transactions on Petri Nets and Other Models of Concurrency VI. Lecture Notes in Computer Science, vol 7400. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-35179-2_6

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  • DOI: https://doi.org/10.1007/978-3-642-35179-2_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-35178-5

  • Online ISBN: 978-3-642-35179-2

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