Modular Modeling of Genetic Circuits in SBML Level 3
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Abstract
The System Biology Markup Language (SBML) Level 2 has been used extensively to make models for biological systems of different complexity. However, the lack of modularity was a serious hurdle for its application to Synthetic Biology where genetic circuits are preferably modeled by putting together the models of their components. SBML Level 3 with the Hierarchical Composition Package overcame this limit. Here, we describe how to realize a modular model for a eukaryotic AND gate in SBML Level 3. Circuit modules, such as transcription units and pools of molecules, are modeled separately and connected, to close the circuit, via Python scripts that utilize the libSBML API. Circuit simulations with COPASI confirm the validity of this modeling approach.
Key words
SBML Level 3 Modules Hierarchy CompositionNotes
Acknowledgements
We acknowledge financial support by the National Natural Science Foundation of China, grant number 31571373.
References
- 1.Marchisio MA, Stelling J (2008) Computational design of synthetic gene circuits with composable parts. Bioinformatics 24(17):1903–1910CrossRefGoogle Scholar
- 2.Marchisio MA (2014) Parts & Pools: a framework for modular design of synthetic gene circuits. Front Bioeng Biotechnol 2:42CrossRefGoogle Scholar
- 3.Mirschel S, Steinmetz K, Rempel M et al (2009) PROMOT: modular modeling for systems biology. Bioinformatics 25(5):687–689CrossRefGoogle Scholar
- 4.Hucka M, Finney A, Sauro HM et al (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19(4):524–531CrossRefGoogle Scholar
- 5.Rodrigo G, Carrera J, Jaramillo A (2007) Asmparts: assembly of biological model parts. Syst Synth Biol 1(4):167–170CrossRefGoogle Scholar
- 6.Hucka M, Bergmann FT, Dräger A et al (2016) The Systems Biology Markup Language (SBML): language specification for Level 3 Version 1 Core. http://sbml.org/specifications/sbml-level-3/version-1/core/release-2-rc2. Accessed 28 Dec 2016
- 7.Smith LP, Hucka M, Hoops S et al (2013) Hierarchical model composition. http://identifiers.org/combine.specifications/sbml.level-3.version-1.comp.version-1.release-3. Accessed 14 Nov 2013
- 8.Marchisio MA (2015) Modular design of synthetic gene circuits with biological parts and pools. In: Marchisio MA (ed) Computational methods in synthetic biology. Methods in molecular biology, vol 1244. Humana Press, New York, pp 137–165CrossRefGoogle Scholar
- 9.Bornstein BJ, Keating SM, Jouraku A et al (2008) LibSBML: an API library for SBML. Bioinformatics 24(6):880–881CrossRefGoogle Scholar
- 10.Drinnenberg IA, Weinberg DE, Xie KT et al (2009) RNAi in budding yeast. Science 326(5952):544–550CrossRefGoogle Scholar
- 11.Marchisio MA (2014) In silico design and in vivo implementation of yeast gene Boolean gates. J Biol Eng 8:6CrossRefGoogle Scholar
- 12.Alon U (2006) An introduction to systems biology. Chapman & Hall/CRC Press, Boca RatonGoogle Scholar
- 13.Hoops S, Sahle S, Gauges R et al (2006) COPASI–a COmplex PAthway SImulator. Bioinformatics 22(24):3067–3074CrossRefGoogle Scholar