Abstract
We present a new approach for the design of a synthetic biological circuit whose behaviour is specified in terms of signal temporal logic (STL) formulae. We first show how to characterise with STL formulae the input/output behaviour of biological modules miming the classical logical gates (AND, NOT, OR). Hence, we provide the regions of the parameter space for which these specifications are satisfied. Given a STL specification of the target circuit to be designed and the networks of its constituent components, we propose a methodology to constrain the behaviour of each module, then identifying the subset of the parameter space in which those constraints are satisfied, providing also a measure of the robustness for the target circuit design. This approach, which leverages recent results on the quantitative semantics of Signal Temporal Logic, is illustrated by synthesising a biological implementation of an half-adder.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Alur, R., Feder, T., Henzinger, T.A.: The benefits of relaxing punctuality. J. ACM (1996)
Bartocci, E., Bortolussi, L., Nenzi, L.: Supplementary material for “A temporal logic approach to modular design of synthetic biological circuits”. CoRR (2013), http://arxiv.org/abs/1306.4493v1
Batt, G., Yordanov, B., Weiss, R., Belta, C.: Robustness analysis and tuning of synthetic gene networks. Bioinformatics 23(18), 2415–2422 (2007)
Beal, J., Weiss, R., Densmore, D., Adler, A., Appleton, E., Babb, J., Bhatia, S., Davidsohn, N., Haddock, T., Loyall, J., Schantz, R., Vasilev, V., Yaman, F.: An End-to-End Workflow for Engineering of Biological Networks from High-Level Specifications. ACS Synth. Biol. 1(8), 317–331 (2012)
Belta, C., Habets, L.C.G.J.M.: Controlling a class of nonlinear systems on rectangles. IEEE Trans. of Automatic Control 51(11), 1749–1759 (2006)
Chen, B.S., Hsu, C.Y., Liou, J.J.: Robust design of biological circuits: evolutionary systems biology approach. J. Biomed. Biotechnol. 2011, 304236 (2011)
Dasika, M.S., Maranas, C.D.: OptCircuit: an optimization based method for computational design of genetic circuits. BMC Syst. Biol. 2, 24 (2008)
Densmore, D., Anderson, J.C.: Combinational logic design in synthetic biology. In: IEEE International Symposium on Circuits and Systems, ISCAS 2009., pp. 301–304 (2009)
Donzé, A.: Breach, A toolbox for verification and parameter synthesis of hybrid systems. In: Touili, T., Cook, B., Jackson, P. (eds.) CAV 2010. LNCS, vol. 6174, pp. 167–170. Springer, Heidelberg (2010)
Donzé, A., Clermont, G., Langmead, C.J.: Parameter synthesis in nonlinear dynamical systems: Application to systems biology. Journal of Computational Biology 17(3), 325–336 (2010)
Donzé, A., Fanchon, E., Gattepaille, L.M., Maler, O., Tracqui, P.: Robustness analysis and behavior discrimination in enzymatic reaction networks. PLoS One 6(9), e24246 (2011)
Donzé, A., Ferrère, T., Maler, O.: Efficient robust monitoring for STL. In: Sharygina, N., Veith, H. (eds.) CAV 2013. LNCS, vol. 8044, pp. 264–279. Springer, Heidelberg (2013)
Donzé, A., Maler, O.: Robust satisfaction of temporal logic over real-valued signals. In: Chatterjee, K., Henzinger, T.A. (eds.) FORMATS 2010. LNCS, vol. 6246, pp. 92–106. Springer, Heidelberg (2010)
Francois, P., Hakim, V.: Design of genetic networks with specified functions by evolution in silico. PNAS 101(2), 580–585 (2004)
Fu, P., Panke, S.: Systems Biology and Synthetic Biology. John Wiley & Sons (2009)
Jones, K.D., Konrad, V., Nickovic, D.: Analog property checkers: A ddr2 case study. Formal Methods in System Design 36(2), 114–130 (2010)
De Jong, H.: Modeling and simulation of genetic regulatory systems: A literature review. Journal of Computational Biology 9, 67–103 (2002)
Karnaugh, M.: The map method for synthesis of combinational logic circuits. Trans. American Institute of Electrical Engineers 72(2) (1953)
Knight, T.: Idempotent vector design for standard assembly of biobricks. Technical Report MIT Synthetic Biology Working Group. MIT (2003)
Madec, M., Lallement, C., Gendrault, Y., Haiech, J.: Design methodology for synthetic biosystems. In: Proc. of MIXDES, pp. 621–626 (2010)
Maler, O., Nickovic, D.: Monitoring temporal properties of continuous signals. In: Lakhnech, Y., Yovine, S. (eds.) FORMATS/FTRTFT 2004. LNCS, vol. 3253, pp. 152–166. Springer, Heidelberg (2004)
Marchisio, M.A., Stelling, J.: Automatic design of digital synthetic gene circuits. PLoS Comput. Biol. 7(2), e1001083 (2011)
Myers, C.J.: Engineering Genetic Circuits. Chapman & Hall/CRC (2009)
Pnueli, A.: The temporal logic of programs. In: IEEE Annual Symposium on Foundations of Computer Science, pp. 46–57 (1977)
Rodrigo, G., Jaramillo, A.: AutoBioCAD: Full Biodesign Automation of Genetic Circuits. ACS Synth. Biol. (November 2012)
Salah, R.B., Bozga, M., Maler, O.: On timing analysis of combinational circuits. In: Larsen, K.G., Niebert, P. (eds.) FORMATS 2003. LNCS, vol. 2791, pp. 204–219. Springer, Heidelberg (2004)
Smith, H.L.: Systems of odes which generate an order preserving flow. A survey of results. SIAM Review 30(1), 87–113 (1988)
Szallasi, Z., Stelling, J., Periwal, V.: System Modelling in Cellular Biology: from concepts to nuts and bolts. The Mit Press (2006)
Terzer, M., Jovanovic, M., Choutko, A., Nikolayeva, O., Korn, A., Brockhoff, D., Zurcher, F., Friedmann, M., Schutz, R., Zitzler, E., Stelling, J., Panke, S.: Design of a biological half adder. IET Synthetic Biology 1(1-2), 53–58 (2007)
Van Kampen, N.G.: Stochastic Processes in Physics and Chemistry. Elsevier (1992)
von Dassow, G., Meir, E., Munro, E.M., Odell, G.M.: The segment polarity network is a robust developmental module. Nature (2000)
Voy, B.H., Scharff, J.A., Perkins, A.D., Saxton, A.M., Borate, B., Chesler, E.J., Branstetter, L.K., Langston, M.A.: Extracting gene networks for low-dose radiation using graph theoretical algorithms. PLoS Comput. Biol. (2006)
Yaman, F., Bhatia, S., Adler, A., Densmore, D., Beal, J.: Automated selection of synthetic biology parts for genetic regulatory networks. ACS Synth. Biol. 1(8), 332–344 (2012)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Bartocci, E., Bortolussi, L., Nenzi, L. (2013). A Temporal Logic Approach to Modular Design of Synthetic Biological Circuits. In: Gupta, A., Henzinger, T.A. (eds) Computational Methods in Systems Biology. CMSB 2013. Lecture Notes in Computer Science(), vol 8130. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40708-6_13
Download citation
DOI: https://doi.org/10.1007/978-3-642-40708-6_13
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-40707-9
Online ISBN: 978-3-642-40708-6
eBook Packages: Computer ScienceComputer Science (R0)