Genetic Design via Combinatorial Constraint Specification.

We present a formal language for specifying via constraints a "design space" of DNA constructs composed of genetic parts, and an algorithm for automatically and correctly creating a novel representation of the space of satisfying designs. The language is simple, captures a large class of design spaces, and possesses algorithms for common operations on design spaces. The flexibility of this approach is demonstrated using a 16-gene nitrogen fixation pathway and genetic logic circuits.

[1]  Adam Arkin,et al.  Setting the standard in synthetic biology , 2008, Nature Biotechnology.

[2]  H. Sauro,et al.  Standard Biological Parts Knowledgebase , 2011, PloS one.

[3]  D. Densmore,et al.  Algorithms for automated DNA assembly , 2010, Nucleic acids research.

[4]  D. Endy.  Foundations for engineering biology , 2005, Nature.

[5]  Jacob Beal,et al.  Model-driven engineering of gene expression from RNA replicons. , 2015, ACS synthetic biology.

[6]  Christopher A. Voigt,et al.  Genetic circuit design automation , 2016, Science.

[7]  Priscilla E. M. Purnick,et al.  The second wave of synthetic biology: from modules to systems , 2009, Nature Reviews Molecular Cell Biology.

[8]  Matthias Köppe,et al.  SBROME: a scalable optimization and module matching framework for automated biosystems design. , 2013, ACS synthetic biology.

[9]  J. Peccoud,et al.  Targeted Development of Registries of Biological Parts , 2008, PloS one.

[10]  Mark Isalan,et al.  Building synthetic gene circuits from combinatorial libraries: screening and selection strategies. , 2013, Molecular bioSystems.

[11]  Swapnil Bhatia,et al.  Functional optimization of gene clusters by combinatorial design and assembly , 2014, Nature Biotechnology.

[12]  Ernst Oberortner,et al.  Web-based software tool for constraint-based design specification of synthetic biological systems. , 2015, ACS synthetic biology.

[13]  Jean Peccoud,et al.  A syntactic model to design and verify synthetic genetic constructs derived from standard biological parts , 2007, Bioinform..

[14]  Nathan J Hillson,et al.  PaR-PaR laboratory automation platform. , 2013, ACS synthetic biology.

[15]  Rajeev Alur,et al.  Formal verification of hybrid systems , 2011, 2011 Proceedings of the Ninth ACM International Conference on Embedded Software (EMSOFT).

[16]  Timothy S. Ham,et al.  Design, implementation and practice of JBEI-ICE: an open source biological part registry platform and tools , 2012, Nucleic acids research.

[17]  R. Weiss,et al.  Automatic Compilation from High-Level Biologically-Oriented Programming Language to Genetic Regulatory Networks , 2011, PloS one.

[18]  Eric Klavins,et al.  Specification and simulation of synthetic multicelled behaviors. , 2012, ACS synthetic biology.

[19]  Nathan J Hillson,et al.  j5 DNA assembly design automation software. , 2012, ACS synthetic biology.

[20]  Ernst Dieter Gilles,et al.  ProMoT: modular modeling for systems biology , 2009, Bioinform..

[21]  Dana S. Scott,et al.  Finite Automata and Their Decision Problems , 1959, IBM J. Res. Dev..

[22]  Chris J. Myers,et al.  Tablet—next generation sequence assembly visualization , 2009, Bioinform..

[23]  Deepak Chandran,et al.  TinkerCell: modular CAD tool for synthetic biology , 2009, Journal of biological engineering.

[24]  Jacob Beal,et al.  Automated selection of synthetic biology parts for genetic regulatory networks. , 2012, ACS synthetic biology.

[25]  Jacob Beal,et al.  An end-to-end workflow for engineering of biological networks from high-level specifications. , 2012, ACS synthetic biology.

[26]  Jacob Beal,et al.  Accurate predictions of genetic circuit behavior from part characterization and modular composition. , 2015, ACS synthetic biology.

[27]  T. Ellis,et al.  Bricks and blueprints: methods and standards for DNA assembly , 2015, Nature Reviews Molecular Cell Biology.

[28]  E. Klavins,et al.  Framework for engineering finite state machines in gene regulatory networks. , 2014, ACS synthetic biology.

[29]  E. Andrianantoandro,et al.  Synthetic biology: new engineering rules for an emerging discipline , 2006, Molecular systems biology.

[30]  Tuval Ben Yehezkel,et al.  Recursive construction of perfect DNA molecules from imperfect oligonucleotides , 2008, Molecular systems biology.

[31]  Tom Ellis,et al.  DNA assembly for synthetic biology: from parts to pathways and beyond. , 2011, Integrative biology : quantitative biosciences from nano to macro.

[32]  Douglas Densmore,et al.  Interactive assembly algorithms for molecular cloning , 2014, Nature Methods.

[33]  Allan Kuchinsky,et al.  The Synthetic Biology Open Language (SBOL) provides a community standard for communicating designs in synthetic biology , 2014, Nature Biotechnology.

[34]  Emma M. B. Weeding,et al.  Eugene – A Domain Specific Language for Specifying and Constraining Synthetic Biological Parts, Devices, and Systems , 2011, PloS one.