Abstract
The mathematical formalism of mass-action chemical reaction networks (CRNs) has been proposed as a mid-level programming language for dynamic molecular systems. Several systematic methods for translating CRNs into domain-level strand displacement (DSD) systems have been developed theoretically, and in some cases demonstrated experimentally. Software that facilitates the simulation of CRNs and DSDs, and that helps automate the construction of DSDs from CRNs, has been instrumental in advancing the field, but as yet has not incorporated the fundamental enabling concept for programming languages and compilers: a rigorous abstraction hierarchy with well-defined semantics at each level, and rigorous correctness proofs establishing the correctness of compilation from a higher level to a lower level. Here, we present a CRN-to-DSD compiler, Nuskell, that makes a first step in this direction. To support the wide range of translation schemes that have already been proposed in the literature, as well as potential new ones that are yet to be proposed, Nuskell provides a domain-specific programming language for translation schemes. A notion of correctness is established on a case-by-case basis using the rate-independent stochastic-level theories of pathway decomposition equivalence and/or CRN bisimulation. The “best” DSD implementation for a given CRN can be found by comparing the molecule size, network size, or simulation behavior for a variety of translation schemes. These features are illustrated with a 3-reaction oscillator CRN and a 32-reaction feedforward boolean circuit CRN.
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
References
Boyken, S.E., Chen, Z., Groves, B., Langan, R.A., Oberdorfer, G., Ford, A., Gilmore, J.M., Xu, C., DiMaio, F., Pereira, J.H., et al.: De novo design of protein homo-oligomers with modular hydrogen-bond network-mediated specificity. Science 352(6286), 680–687 (2016)
Cardelli, L.: Strand algebras for DNA computing. Nat. Comput. 10(1), 407–428 (2011)
Cardelli, L.: Two-domain DNA strand displacement. Math. Struct. Comput. Sci. 23(02), 247–271 (2013)
Chen, Y.J., Dalchau, N., Srinivas, N., Phillips, A., Cardelli, L., Soloveichik, D., Seelig, G.: Programmable chemical controllers made from DNA. Nat. Nanotechnol. 8(10), 755–762 (2013)
Cook, M., Soloveichik, D., Winfree, E., Bruck, J.: Programmability of chemical reaction networks. In: Condon, A., Harel, D., Kok, J., Salomaa, A., Winfree, E. (eds.) Algorithmic Bioprocesses. Natural Computing Series, pp. 543–584. Springer, Heidelberg (2009)
Flamm, C., Fontana, W., Hofacker, I.L., Schuster, P.: RNA folding at elementary step resolution. RNA 6, 325–338 (2000)
Grun, C., Sarma, K., Wolfe, B., Shin, S.W., Winfree, E.: A domain-level DNA strand displacement reaction enumerator allowing arbitrary non-pseudoknotted secondary structures. arXiv:1505.03738 (2014)
Hochrein, L.M., Schwarzkopf, M., Shahgholi, M., Yin, P., Pierce, N.A.: Conditional dicer substrate formation via shape and sequence transduction with small conditional RNAs. J. Am. Chem. Soc. 135(46), 17322–17330 (2013)
Johnson, R.F., Dong, Q., Winfree, E.: Verifying chemical reaction network implementations: a bisimulation approach. In: Rondelez, Y., Woods, D. (eds.) DNA 2016. LNCS, vol. 9818, pp. 114–134. Springer, Cham (2016). doi:10.1007/978-3-319-43994-5_8
Lakin, M.R., Parker, D., Cardelli, L., Kwiatkowska, M., Phillips, A.: Design and analysis of DNA strand displacement devices using probabilistic model checking. J. Roy. Soc. Interface 9, 1470–1485 (2012)
Lakin, M.R., Stefanovic, D., Phillips, A.: Modular verification of chemical reaction network encodings via serializability analysis. Theoret. Comput. Sci. 632, 21–42 (2016)
Lakin, M.R., Youssef, S., Cardelli, L., Phillips, A.: Abstractions for DNA circuit design. J. Roy. Soc. Interface 9(68), 470–486 (2012)
Qian, L., Soloveichik, D., Winfree, E.: Efficient Turing-universal computation with DNA polymers. In: Sakakibara, Y., Mi, Y. (eds.) DNA 2010. LNCS, vol. 6518, pp. 123–140. Springer, Heidelberg (2011). doi:10.1007/978-3-642-18305-8_12
Qian, L., Winfree, E.: Scaling up digital circuit computation with DNA strand displacement cascades. Science 332(6034), 1196–1201 (2011)
Schaeffer, J.M., Thachuk, C., Winfree, E.: Stochastic simulation of the kinetics of multiple interacting nucleic acid strands. In: Phillips, A., Yin, P. (eds.) DNA 2015. LNCS, vol. 9211, pp. 194–211. Springer, Cham (2015). doi:10.1007/978-3-319-21999-8_13
Shin, S.W.: Compiling and verifying DNA-based chemical reaction network implementations. Master’s thesis, Caltech (2011)
Soloveichik, D., Cook, M., Winfree, E., Bruck, J.: Computation with finite stochastic chemical reaction networks. Nat. Comput. 7(4), 615–633 (2008)
Soloveichik, D., Seelig, G., Winfree, E.: DNA as a universal substrate for chemical kinetics. Proc. Natl. Acad. Sci. 107(12), 5393–5398 (2010)
Srinivas, N.: Programming chemical kinetics: engineering dynamic reaction networks with DNA strand displacement. Ph.D. thesis, Caltech (2015)
Srinivas, N., Parkin, J., Seelig, G., Winfree, E., Soloveichik, D.: Enzyme-free nucleic acid dynamical systems. bioRxiv (2017). http://biorxiv.org/content/early/2017/05/16/138420
Thubagere, A.J., Thachuk, C., Berleant, J., Johnson, R.F., Ardelean, D.A., Cherry, K.M., Qian, L.: Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components. Nat. Commun. 8, 14373 (2017)
Zhang, D.Y., Seelig, G.: Dynamic DNA nanotechnology using strand-displacement reactions. Nat. Chem. 3(2), 103–113 (2011)
Acknowledgements
We thank the U.S. National Science Foundation for support: NSF Grant CCF-1213127 and NSF Grant CCF-1317694 (“The Molecular Programming Project”). The Gordon and Betty Moore Foundation’s Programmable Molecular Technology Initiative (PMTI). SB is funded by the Caltech Biology and Biological Engineering Division Fellowship. SWS’s current address is Google, Mountain View, California. QD’s current address is Epic Systems, Madison, Wisconsin.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this paper
Cite this paper
Badelt, S., Shin, S.W., Johnson, R.F., Dong, Q., Thachuk, C., Winfree, E. (2017). A General-Purpose CRN-to-DSD Compiler with Formal Verification, Optimization, and Simulation Capabilities. In: Brijder, R., Qian, L. (eds) DNA Computing and Molecular Programming. DNA 2017. Lecture Notes in Computer Science(), vol 10467. Springer, Cham. https://doi.org/10.1007/978-3-319-66799-7_15
Download citation
DOI: https://doi.org/10.1007/978-3-319-66799-7_15
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-66798-0
Online ISBN: 978-3-319-66799-7
eBook Packages: Computer ScienceComputer Science (R0)