DeviceEditor visual biological CAD canvas

Journal of Biological Engineering

Nathan J Hillson²  Jay D Keasling¹  Timothy S Ham⁴  Douglas Densmore³  Joanna Chen² 

[1] Department of Bioengineering, University of California, Berkeley, USA;Physical Bioscience Division, Lawrence Berkeley National Lab, Berkeley, CA 94720, USA;Department of Electrical and Computer Engineering, Boston University, Boston, MA 02215, USA;Sandia National Laboratories, Livermore, CA 94550, USA

关键词: DNA assembly;    Combinatorial library;    Design specification rules;    Correct-by-construction design;    Visual design abstraction;    bioCAD;   

Others  :  813540
DOI  :  10.1186/1754-1611-6-1

 received in 2011-11-15, accepted in 2012-02-28,  发布年份 2012

【 摘 要 】

Background

Biological Computer Aided Design (bioCAD) assists the de novo design and selection of existing genetic components to achieve a desired biological activity, as part of an integrated design-build-test cycle. To meet the emerging needs of Synthetic Biology, bioCAD tools must address the increasing prevalence of combinatorial library design, design rule specification, and scar-less multi-part DNA assembly.

Results

We report the development and deployment of web-based bioCAD software, DeviceEditor, which provides a graphical design environment that mimics the intuitive visual whiteboard design process practiced in biological laboratories. The key innovations of DeviceEditor include visual combinatorial library design, direct integration with scar-less multi-part DNA assembly design automation, and a graphical user interface for the creation and modification of design specification rules. We demonstrate how biological designs are rendered on the DeviceEditor canvas, and we present effective visualizations of genetic component ordering and combinatorial variations within complex designs.

Conclusions

DeviceEditor liberates researchers from DNA base-pair manipulation, and enables users to create successful prototypes using standardized, functional, and visual abstractions. Open and documented software interfaces support further integration of DeviceEditor with other bioCAD tools and software platforms. DeviceEditor saves researcher time and institutional resources through correct-by-construction design, the automation of tedious tasks, design reuse, and the minimization of DNA assembly costs.

【 授权许可】

   
2012 Chen et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Nielsen J, Keasling JD: Synergies between synthetic biology and metabolic engineering. Nat Biotechnol 2011, 29:693-695.
• [2]MacDonald JT, Barnes C, Kitney RI, Freemont PS, Stan GB: Computational design approaches and tools for synthetic biology. Integr Biol (Camb) 2011, 3:97-108.
• [3]Chandran D, Bergmann FT, Sauro HM, Densmore D: Computer-aided design for synthetic biology. In Design and Analysis of Bio-molecular Circuits. 1st edition. Edited by Koeppl H, Densmore D, di Bernardo M, Setti G. New York, Springer-Verlag; 2011:203-224.
• [4]Lux MW, Bramlett BW, Ball DA, Peccoud J: Genetic design automation: engineering fantasy or scientific renewal? Trends Biotechnol 2012, 30:120-126.
• [5]Bates JT, Chivian D, Arkin AP: GLAMM: Genome-Linked Application for Metabolic Maps. Nucleic Acids Res 2011, 39:W400-W405.
• [6]Chandran D, Bergmann FT, Sauro HM: TinkerCell: modular CAD tool for synthetic biology. J Biol Eng 2009, 3:19. BioMed Central Full Text
• [7]Hucka M, Finney A, Sauro HM, Bolouri H, Doyle J, Kitano H: The ERATO Systems Biology Workbench: enabling interaction and exchange between software tools for computational biology. Pac Symp Biocomput 2002, 450-461.
• [8]Xia B, Bhatia S, Bubenheim B, Dadgar M, Densmore D, Anderson JC: Developer's and user's guide to Clotho v2.0 A software platform for the creation of synthetic biological systems. Methods Enzymol 2011, 498:97-135.
• [9]Hill AD, Tomshine JR, Weeding EM, Sotiropoulos V, Kaznessis YN: SynBioSS: the synthetic biology modeling suite. Bioinformatics 2008, 24:2551-2553.
• [10]Cai Y, Wilson ML, Peccoud J: GenoCAD for iGEM: a grammatical approach to the design of standard-compliant constructs. Nucleic Acids Res 2010, 38:2637-2644.
• [11]Leguia M, Brophy J, Densmore D, Anderson JC: Automated assembly of standard biological parts. Methods Enzymol 2011, 498:363-397.
• [12]Hillson NJ, Rosengarten RD, Keasling JD: j5 DNA assembly design automation software. ACS Synthetic Biology 2012, 1:14-21.
• [13]Ellis T, Adie T, Baldwin GS: DNA assembly for synthetic biology: from parts to pathways and beyond. Integr Biol (Camb) 2011, 3:109-118.
• [14]Hillson NJ: DNA Assembly Method Standardization for Synthetic Biomolecular Circuits and Systems. In Design and Analysis of Bio-molecular Circuits. 1st edition. Edited by Koeppl H, Densmore D, di Bernardo M, Setti G. New York, Springer-Verlag; 2011:295-314.
• [15]Salis HM, Mirsky EA, Voigt CA: Automated design of synthetic ribosome binding sites to control protein expression. Nat Biotechnol 2009, 27:946-950.
• [16]Synthetic Biology Open Language standard [http://www.sbolstandard.org/] webcite
• [17]Quan J, Tian J: Circular polymerase extension cloning for high-throughput cloning of complex and combinatorial DNA libraries. Nat Protoc 2011, 6:242-251.
• [18]Ramon A, Smith HO: Single-step linker-based combinatorial assembly of promoter and gene cassettes for pathway engineering. Biotechnol Lett 2011, 33:549-555.
• [19]Shao Z, Luo Y, Zhao H: Rapid characterization and engineering of natural product biosynthetic pathways via DNA assembler. Mol Biosyst 2011, 7:1056-1059.
• [20]Bilitchenko L, Liu A, Cheung S, Weeding E, Xia B, Leguia M, Anderson JC, Densmore D: Eugene-a domain specific language for specifying and constraining synthetic biological parts, devices, and systems. PLoS One 2011, 6:e18882.
• [21]Spectacles software [http://2009.igem.org/Team:Berkeley_Software/Spectacles] webcite
• [22]Beal J, Lu T, Weiss R: Automatic compilation from high-level biologically-oriented programming language to genetic regulatory networks. PLoS One 2011, 6:e22490.
• [23]DeviceEditor user's manual [http://j5.jbei.org/DeviceEditor_manual/index.html] webcite
• [24]DeviceEditor software [http://j5.jbei.org/bin/deviceeditor.pl] webcite
• [25]Synthetic Biology Open Language visual standard [http://www.sbolstandard.org/specification/extensions] webcite
• [26]Shetty RP, Endy D, Knight TF Jr: Engineering BioBrick vectors from BioBrick parts. J Biol Eng 2008, 2:5. BioMed Central Full Text
• [27]Lee TS, Krupa RA, Zhang F, Hajimorad M, Holtz WJ, Prasad N, Lee SK, Keasling JD: BglBrick vectors and datasheets: a synthetic biology platform for gene expression. J Biol Eng 2011, 5:12. BioMed Central Full Text
• [28]jbei-seq sequence format XML schema [http://gd-ice.googlecode.com/git/docs/seq.xsd] webcite
• [29]A plasmid Editor (ApE) software [http://biologylabs.utah.edu/jorgensen/wayned/ape/] webcite
• [30]Redding-Johanson AM, Batth TS, Chan R, Krupa R, Szmidt HL, Adams PD, Keasling JD, Lee TS, Mukhopadhyay A, Petzold CJ: Targeted proteomics for metabolic pathway optimization: application to terpene production. Metab Eng 2011, 13:194-203.
• [31]Ajikumar PK, Xiao WH, Tyo KE, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stephanopoulos G: Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 2010, 330:70-74.
• [32]Dunlop MJ, Dossani ZY, Szmidt HL, Chu HC, Lee TS, Keasling JD, Hadi MZ, Mukhopadhyay A: Engineering microbial biofuel tolerance and export using efflux pumps. Mol Syst Biol 2011, 7:487.
• [33]VectorEditor stand-alone software [https://public-registry.jbei.org/static/vesa/VectorEditor.html] webcite
• [34]VectorEditor Project [http://code.google.com/p/vectoreditor/] webcite
• [35]j5 web-form interface [http://j5.jbei.org/bin/j5_entry_form.pl] webcite
• [36]Clotho website [http://clothocad.org] webcite
• [37]GenoCAD website [http://genocad.org] webcite
• [38]libSBOLxml library [http://github.com/SynBioDex/libSBOLxml] webcite
• [39]Public instance of the JBEI Parts Registry [http://public-registry.jbei.org] webcite
• [40]DeviceEditor end-user license [http://j5.jbei.org/index.php/License] webcite
• [41]Public j5 web-server [http://j5.jbei.org] webcite
• [42]Mediawiki software [http://www.mediawiki.org] webcite
• [43]PostgreSQL database software [http://www.postgresql.org/] webcite
• [44]Perl programming language [http://www.perl.org/] webcite
• [45]Adobe Flex framework [http://www.adobe.com/products/flex.html] webcite
• [46]Degrafa declarative graphics framework [http://www.degrafa.org/] webcite
• [47]PureMVC framework [http://trac.puremvc.org/PureMVC] webcite
• [48]AS3 Zip library [http://nochump.com/blog/archives/15] webcite
• [49]flex-object-handles library [http://code.google.com/p/flex-object-handles/] webcite
• [50]as3corelib library [https://github.com/mikechambers/as3corelib] webcite
• [51]as3-rpclib library [http://code.google.com/p/as3-rpclib/] webcite
• [52]Circus Ponies Notebook software [http://www.circusponies.com/] webcite
• [53]Apple QuickTime software [http://www.apple.com/quicktime/] webcite
• [54]DeviceEditor clipboard interface and XML design file specifications [http://j5.jbei.org/DeviceEditor_manual/pages/122.html] webcite
• [55]j5 input file specifications [http://j5.jbei.org/j5manual/pages/38.html] webcite