Ernst Oberortner
Abstract
Synthetic Biology is an engineering discipline where parts of DNA sequences are composed into novel, complex systems that execute a desired biological function. Functioning and well-behaving biological systems adhere to a certain set of biological “rules”. Data exchange standards and Bio-Design Automation (BDA) tools support the organization of part libraries and the exploration of rule-compliant compositions. In this work, we formally define a design specification language, enabling the integration of biological rules into the Synthetic Biology engineering process. The supported rules are divided into five categories: Counting, Pairing, Positioning, Orientation, and Interactions. We formally define the semantics of each rule, characterize the language's expressive power, and perform a case study in that we iteratively design a genetic Priority Encoder circuit following two alternative paradigms—rule-based and template-driven. Ultimately, we touch a method to approximate the complexity and time to computationally enumerate all rule-compliant designs. Our specification language may or may not be expressive enough to capture all designs that a Synthetic Biologist might want to describe, or the complexity one might find through experiments. However, computational support for the acquisition, specification, management, and application of biological rules is inevitable to understand the functioning of biology.
- E. Andrianantoandro, S. Basu, D. K. Karig, and R. Weiss. 2006. Synthetic biology: New engineering rules for an emerging discipline. Molec. Syst. Biol. 2. DOI: http://dx.doi.org/10.1038/msb4100073Google Scholar
- Swapnil Bhatia and Douglas Densmore. 2013. Pigeon: A design visualizer for synthetic biology. ACS Synthet. Biol. 2, 6, 348--350. DOI: http://dx.doi.org/10.1021/sb400024sGoogle ScholarCross Ref
- Lesia Bilitchenko, Adam Liu, Sherine Cheung, Emma Weeding, Bing Xia, Mariana Leguia, J. Christopher Anderson, and Douglas Densmore. 2011. Eugene: A domain specific language for specifying and constraining synthetic biological parts, devices, and systems. PLoS ONE 6, 4 (April), e18882. DOI: http://dx.doi.org/10.1371/journal.pone.0018882Google ScholarCross Ref
- Lukasz J. Bugaj and David V. Schaffer. 2012. Bringing next-generation therapeutics to the clinic through synthetic biology. Curr. Opin. Chem. Biol. 16, 3, 355--361. DOI: http://dx.doi.org/10.1016/j.cbpa.2012.04.009Google ScholarCross Ref
- Stefano Cardinale and Adam Paul Arkin. 2012. Contextualizing context for synthetic biology—identifying causes of failure of synthetic biological systems. Biotech. J. 7, 7, 856--866. DOI: http://dx.doi.org/10.1002/biot.201200085Google ScholarCross Ref
- Joanna Chen, Douglas Densmore, Timothy Ham, Jay Keasling, and Nathan Hillson. 2012. DeviceEditor visual biological CAD canvas. J. Biol. Eng. 6, 1, 1. DOI: http://dx.doi.org/10.1186/1754-1611-6-1Google ScholarCross Ref
- Su Chen, Tomasz Imielinski, Karin Johnsgard, Donald Smith, and Mario Szegedy. 2006. A dichotomy theorem for typed constraint satisfaction problems. In Proceedings of the Symposium on the Theory and Applications of Satisfiability Testing (SAT'06). Armin Biere and Carla P. Gomes (Eds.), Lecture Notes in Computer Science, vol. 4121, Springer, Berlin Heidelberg, 226--239. DOI: http://dx.doi.org/10.1007/11814948_23 Google ScholarDigital Library
- Michael J. Czar, Yizhi Cai, and Jean Peccoud. 2009. Writing DNA with GenoCAD. Nucl. Acids Res. 37, Web-Server-Issue (2009), 40--47.Google Scholar
- Douglas Densmore and Soha Hassoun. 2012. Design automation for synthetic biological systems. IEEE Design Test Comput. 29, 3, 7--20.Google ScholarCross Ref
- D. Densmore, J. T. Kittleson, L. Bilitchenko, A. Liu, and J. C. Anderson. 2010. Rule based constraints for the construction of genetic devices. In Proceedings of the IEEE International Symposium on Circuits and Systems (ISCAS). 557--560. DOI: http://dx.doi.org/10.1109/ISCAS.2010.5537540Google Scholar
- Drew Endy. 2005. Foundations for engineering biology. Nature 438, 7067, 449--453. DOI: http://dx.doi.org/10.1038/nature04342Google Scholar
- Michal Galdzicki, Kevin P. Claney, Ernst Oberortner, et al. 2014. The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology. Nat. Biotech. 32, 6 (June), 545--550. DOI: http://dx.doi.org/10.1038/nbt.2891Google ScholarCross Ref
- T. S. Gardner, C. R. Cantor, and J. J. Collins. 2000. Construction of a genetic toggle switch in Escherichia coli. Nature 403, 6767, 339--342. DOI: http://dx.doi.org/10.1038/35002131Google Scholar
- John E. Hopcroft, Rajeev Motwani, and Jeffrey D. Ullman. 2006. Introduction to Automata Theory, Languages, and Computation (3rd Ed.). Addison-Wesley Longman Publishing Co., Inc., Boston, MA. Google ScholarDigital Library
- Julius B. Lucks, Lei Qi, Weston R. Whitaker, and Adam P. Arkin. 2008. Toward scalable parts families for predictable design of biological circuits. Curr. Opin. Microbiol. 11, 6, 567--573. DOI: http://dx.doi.org/10.1016/j.mib.2008.10.002, Growth and Development: Eukaryotes/Prokaryotes.Google ScholarCross Ref
- R. McNaughton and S. Papert. 1971. Counter-free automata. Tech. Rep. 65, MIT.Google Scholar
- Oliver Purcell, Jean Peccoud, and Timothy K. Lu. 2014. Rule-based design of synthetic transcription factors in eukaryotes. ACS Synthet. Biol. 3, 10, 737--744. DOI: http://dx.doi.org/10.1021/sb400134kGoogle ScholarCross Ref
- Priscilla E. M. Purnick and Ron Weiss. 2009. The second wave of synthetic biology: From modules to systems. Nat. Reviews. Mole. Cell Biol. 10, 410--22. DOI: http://dx.doi.org/10.1038/nrm2698Google ScholarCross Ref
- Adrian Randall, Patrick Guye, Saurabh Gupta, Xavier Duportet, and Ron Weiss. 2011. Chapter Seven -- Design and connection of robust genetic circuits. In Synthetic Biology, Part A, Chris Voigt (Ed.), Methods in Enzymology, vol. 497, Academic Press, 159--186. DOI: http://dx.doi.org/10.1016/B978-0-12-385075-1.00007-XGoogle Scholar
- Warren C. Ruder, Ting Lu, and James J. Collins. 2011. Synthetic biology moving into the clinic. Science 333, 6047, 1248--1252. DOI: http://dx.doi.org/10.1126/science.1206843Google Scholar
- Sumitra Shankar and M. Radhakrishna Pillai. 2011. Translating cancer research by synthetic biology. Molec. BioSyst. 7, 6, 1802--1810. DOI: http://dx.doi.org/10.1039/C1MB05016HGoogle ScholarCross Ref
- Alvin Tamsir, Jeffrey J. Tabor, and Christopher A. Voigt. 2011. Robust multicellular computing using genetically encoded NOR gates and chemical “wires”. Nature 469, 7329, 212--215. DOI: http://dx.doi.org/10.1038/nature09565Google Scholar
Index Terms
- A Rule-Based Design Specification Language for Synthetic Biology
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