Abstract
We propose a new methodology for identification and analysis of discrete gene networks as defined by René Thomas, supported by a tool chain: (i) given a Thomas network with partially known kinetic parameters, we reduce the number of acceptable parametrizations to those that fit time-series measurements and reflect other known constraints by an improved technique of coloured LTL model checking performing efficiently on Thomas networks in distributed environment; (ii) we introduce classification of acceptable parametrizations to identify most optimal ones; (iii) we propose two ways of visualising parametrizations dynamics wrt time-series data. Finally, computational efficiency is evaluated and the methodology is validated on bacteriophage λ case study.
Keywords
- Thomas network
- parameter identification
- model checking
This work has been supported by the Czech Grant Agency grant No. GAP202/11/0312.
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References
Baier, C., Katoen, J.-P.: Principles of Model Checking. The MIT Press (2008)
Barnat, J., Brim, L., Krejci, A., Streck, A., Safranek, D., Vejnar, M., Vejpustek, T.: On Parameter Synthesis by Parallel Model Checking. IEEE/ACM Transactions on Computational Biology and Bioinformatics 9(3), 693–705 (2012)
Batt, G., Page, M., Cantone, I., Goessler, G., Monteiro, P., de Jong, H.: Efficient parameter search for qualitative models of regulatory networks using symbolic model checking. Bioinformatics 26(18), i603–i610 (2010)
Bernot, G., Comet, J.-P., Richard, A., Guespin, J.: Application of formal methods to biological regulatory networks: Extending Thomas’ asynchronous logical approach with temporal logic. Journal of Theoretical Biology 229(3), 339–347 (2004)
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)
Cline, M., et al.: Integration of biological networks and gene expression data using Cytoscape. Nat. Protocols 2(10), 2366–2382 (2007)
Corblin, F., Fanchon, E., Trilling, L., Chaouiya, C., Thieffry, D.: Automatic Inference of Regulatory and Dynamical Properties from Incomplete Gene Interaction and Expression Data. In: Lones, M.A., Smith, S.L., Teichmann, S., Naef, F., Walker, J.A., Trefzer, M.A. (eds.) IPCAT 2012. LNCS, vol. 7223, pp. 25–30. Springer, Heidelberg (2012)
Corblin, F., et al.: A declarative constraint-based method for analyzing discrete genetic regulatory networks. Biosystems 98(2), 91–104 (2009)
de Jong, H.: Modeling and Simulation of Genetic Regulatory Systems: A Literature Review. Journal of Computational Biology 9(1), 67–103 (2002)
Fauré, A., Naldi, A., Chaouiya, C., Thieffry, D.: Dynamical analysis of a generic boolean model for the control of the mammalian cell cycle. In: ISMB (Supplement of Bioinformatics) 2006, pp. 124–131 (2006)
Helikar, T., Konvalina, J., Heidel, J., Rogers, J.A.: Emergent decision-making in biological signal transduction networks. Proceedings of the National Academy of Sciences 105(6), 1913–1918 (2008)
Klarner, H., Siebert, H., Bockmayr, A.: Time series dependent analysis of unparametrized thomas networks. IEEE/ACM Transactions on Computational Biology and Bioinformatics 99(PrePrints) (2012)
Klarner, H., Streck, A., Safranek, D., Kolcak, J., Siebert, H.: Parameter identification and model ranking of Thomas networks. Technical Report FIMU-RS-2012-03, Masaryk University (2012)
Laubenbacher, R., Mendes, P.: A discrete approach to top-down modeling of biochemical networks. In: Kriete, A., Eils, R. (eds.) Computational Systems Biology, pp. 229–247. Elsevier Academic Press (2005)
Lee, W.-P., Tzou, W.-S.: Computational methods for discovering gene networks from expression data. Briefings in Bioinformatics 10(4), 408–423 (2009)
Naldi, A., Remy, E., Thieffry, D., Chaouiya, C.: Dynamically consistent reduction of logical regulatory graphs. Theor. Comput. Sci. 412(21), 2207–2218 (2011)
Richard, A.: SMBioNet-1.4 User manual (2005)
Sánchez, L., Thieffry, D.: A logical analysis of the drosophila gap-gene system. Journal of Theoretical Biology 211(2), 115–141 (2001)
Siebert, H., Bockmayr, A.: Incorporating Time Delays into the Logical Analysis of Gene Regulatory Networks. In: Priami, C. (ed.) CMSB 2006. LNCS (LNBI), vol. 4210, pp. 169–183. Springer, Heidelberg (2006)
Thieffry, D., Thomas, R.: Dynamical behaviour of biological regulatory networks II. Immunity control in bacteriophage lambda. Bulletin of Mathematical Biology 57, 277–297 (1995)
Thomas, R.: Regulatory networks seen as asynchronous automata: A logical description. Journal of Theoretical Biology 153(1), 1–23 (1991)
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Klarner, H., Streck, A., Šafránek, D., Kolčák, J., Siebert, H. (2012). Parameter Identification and Model Ranking of Thomas Networks. In: Gilbert, D., Heiner, M. (eds) Computational Methods in Systems Biology. CMSB 2012. Lecture Notes in Computer Science(), vol 7605. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33636-2_13
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DOI: https://doi.org/10.1007/978-3-642-33636-2_13
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