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Issue No.05 - Sept.-Oct. (2012 vol.9)
pp: 1338-1351
Hannes Klarner , DFG Res. Center Matheon, Freie Univ. Berlin, Berlin, Germany
Heike Siebert , DFG Res. Center Matheon, Freie Univ. Berlin, Berlin, Germany
Alexander Bockmayr , DFG Res. Center Matheon, Freie Univ. Berlin, Berlin, Germany
ABSTRACT
This paper is concerned with the analysis of labeled Thomas networks using discrete time series. It focuses on refining the given edge labels and on assessing the data quality. The results are aimed at being exploitable for experimental design and include the prediction of new activatory or inhibitory effects of given interactions and yet unobserved oscillations of specific components in between specific sampling intervals. On the formal side, we generalize the concept of edge labels and introduce a discrete time series interpretation. This interpretation features two original concepts: 1) Incomplete measurements are admissible, and 2) it allows qualitative assumptions about the changes in gene expression by means of monotonicity. On the computational side, we provide a Python script, erda.py, that automates the suggested workflow by model checking and constraint satisfaction. We illustrate the workflow by investigating the yeast network IRMA.
INDEX TERMS
time series, biology computing, cellular biophysics, genetics, genomics, microorganisms, oscillations, sampling methods, yeast network IRMA, time series dependent analysis, unparametrized Thomas networks, data quality, inhibitory effects, activatory effects, oscillations, sampling intervals, discrete time series interpretation, gene expression, monotonicity, Python script, model checking, Time series analysis, Regulators, Computational modeling, Time measurement, Bioinformatics, Computational biology, Labeling, constraint satisfaction., Time series analysis, model checking, temporal logic, biology and genetics
CITATION
Hannes Klarner, Heike Siebert, Alexander Bockmayr, "Time Series Dependent Analysis of Unparametrized Thomas Networks", IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol.9, no. 5, pp. 1338-1351, Sept.-Oct. 2012, doi:10.1109/TCBB.2012.61
REFERENCES
[1] J. Barnat, L. Brim, A. Krejci, A. Streck, D. Safranek, M. Vejnar, and T. Vejpustek, "On Parameter Synthesis by Parallel Model Checking," IEEE/ACM Trans. Computational Biology and Bioinformatics, vol. 9, no. 3, pp. 693-705, May/June 2012.
[2] G. Batt, M. Page, I. Cantone, G. Goessler, P. Monteiro, and H. de Jong, "Efficient Parameter Search for Qualitative Models of Regulatory Networks Using Symbolic Model Checking," Bioinformatics, vol. 26, pp. i603-i610, Sept. 2010.
[3] G. Bernot, J.-P. Comet, A. Richard, and J. Guespin, "Application of Formal Methods to Biological Regulatory Networks: Extending Thomas' Asynchronous Logical Approach with Temporal Logic," J. Theoretical Biology, vol. 229, no. 3, pp. 339-347, 2004.
[4] I. Cantone, L. Marucci, F. Iorio, M.A. Ricci, V. Belcastro, M. Bansal, S. Santini, M. Di Bernardo, D. Di Bernardo, and M.P. Cosma, "A Yeast Synthetic Network for in Vivo Assessment of Reverse-Engineering and Modeling Approaches," Cell, vol. 137, no. 1, pp. 172-181, 2009.
[5] N. Chabrier-Rivier, M. Chiaverini, V. Danos, F. Fages, and V. Schächter, "Modeling and Querying Biomolecular Interaction Networks," Theoretical Computer Science, vol. 325, no. 1, pp. 25-44, 2004.
[6] C. Chaouiya, E. Remy, B. Mossé, and D. Thieffry, "Qualitative Analysis of Regulatory Graphs: A Computational Tool Based on a Discrete Formal Framework," Proc. First Multidisciplinary Int'l Symp. Positive Systemsd Applications, L. Benvenuti, A. De Santis, and L. Farina, eds., pp. 830-832, 2003.
[7] A. Cimatti, E.M. Clarke, E. Giunchiglia, F. Giunchiglia, M. Pistore, M. Roveri, R. Sebastiani, and A. Tacchella, "Nusmv 2: An Opensource Tool for Symbolic Model Checking," Proc. 14th Int'l Conf. Computer Aided Verification (CAV '02), pp. 359-364, 2002.
[8] F. Corblin, E. Fanchon, and L. Trilling, "Applications of a Formal Approach to Decipher Discrete Genetic Networks," BMC Bioinformatics, vol. 11, article 385, July 2010.
[9] E.S. Dimitrova, L.D. Garcia-Puente, F. Hinkelmann, A.S. Jarrah, R.C. Laubenbacher, B. Stigler, M. Stillman, and P. Vera-Licona, "Parameter Estimation for Boolean Models of Biological Networks," Theoretical Computer Science, vol. 412, no. 26, pp. 2816-2826, 2011.
[10] E.S. Dimitrova, J.J. McGee, and R.C. Laubenbacher, "Discretization of Time Series Data," J. Computational Biology, vol. 17, no. 6, pp. 853-868, 2010.
[11] J. Fromentin, J.-P. Comet, P.L. Gall, and O. Roux, "Analysing Gene Regulatory Networks by Both Constraint Programming and Model-Checking." Proc. IEEE 29th Ann. Int'l Conf. Eng. in Medicine and Biology Soc. (EMBC '07), pp. 4595-4598, Aug. 2007.
[12] M. Huth and M. Ryan, Logic in Computer Science: Modelling and Reasoning About Systems. Cambridge Univ. Press, 2004.
[13] H. Klarner, H. Siebert, and A. Bockmayr, "Parameter Inference for Asynchronous Logical Networks Using Discrete Time Series," Proc. Ninth Int'l Conf. Computational Methods in Systems Biology (CMSB '11), pp. 121-130, 2011.
[14] S. Meiers, "Graph Traversal Versus Model Checking in Deciding Compatibility of Time Series with Logical Networks," bachelor's thesis, Freie Universität Berlin, 2011.
[15] P.T. Monteiro, D. Ropers, R. Mateescu, A.T. Freitas, and H. de Jong, "Temporal Logic Patterns for Querying Dynamic Models of Cellular Interaction Networks," Bioinformatics, vol. 24, no. 16, pp. i227-i233, 2008.
[16] C. Müssel, M. Hopfensitz, and H.A. Kestler, "Boolnet - An R Package for Generation, Reconstruction, and Analysis of Boolean Networks," Bioinformatics, vol. 26, no. 10, pp. 1378-1380, 2010.
[17] A. Richard, "Negative Circuits and Sustained Oscillations in Asynchronous Automata Networks," Advances in Applied Math., vol. 44, no. 4, pp. 378-392, 2009.
[18] I. Shmulevich and W. Zhang, "Binary Analysis and Optimization-Based Normalization of Gene Expression Data," Bioinformatics, vol. 18, no. 4, pp. 555-565, 2002.
[19] R. Thomas, "Regulatory Networks Seen as Asynchronous Automata: A Logical Description," J. Theoretical Biology, vol. 153, no. 1, pp. 1-23, 1991.
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