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==Alternatives==
==Alternatives==
The most common alternatives to GenoCAD are [[Proto]], [[GEC]] and [[EuGene]]<ref name="Habibi"/>
Apart from '''GenoCAD''' several different approaches have been proposed to approach DNA sequences as languages in order to program biological systems.<ref name="A step-by-step" />
{| class="wikitable"
*TinkerCell http://www.tinkercell.com/
|-
*SynBIOSS http://synbioss.sourceforge.net/
! Tool !! Advantages !! Disadvantages
*GEC Genetic Engineering of Cells http://research.microsoft.com/en-us/projects/gec/
|-
*Clotho http://www.clothocad.org/
!GEC
*Eugene<ref>
|
{{Cite doi|10.1371/journal.pone.0018882}}
*Supports [[SBML]]<ref name="Marchiso">Marchisio, M. A., & Stelling, J. (2009). Computational design tools for synthetic biology. Current opinion in biotechnology, 20(4), 479-485.</ref>
⚫
</ref>
*Designer only needs to know basic part types and determine constraints <ref>Habibi, N., Mohd Hashim, S. Z., Rodriguez, C. A., & Samian, M. R. (2013). A Review of CADs, Languages and Data Models for Synthetic Biology. Jurnal Teknologi, 63(1).</ref>
||
*Does not support [[Synthetic Biology Open Language | SBOL ]]<ref name="Pedersen">Pedersen, M. (2010). Modular languages for systems and synthetic biology.</ref>
|-
!EuGene
|
*Interfacing with other simulation and assembly tools<ref name="Habibi">Habibi, N., Mohd Hashim, S. Z., Rodriguez, C. A., & Samian, M. R. (2013). A Review of CADs, Languages and Data Models for Synthetic Biology. Jurnal Teknologi, 63(1).</ref>
||
*No [[graphical user interface]]<ref name="Habibi"/>
*No web based interface<ref name="Habibi"/>
|-
!Proto
|
*Supports [[SBML]]<ref name="Habibi"/>
*Choice of molecules and sequences can be made by other programs<ref name="Habibi"/>
*Integration capability with some other languages<ref name="Habibi"/>
||
*Relatively hard to learn <ref name="Habibi"/>
*Results are less efficient <ref>{{cite encyclopedia
|last1=Beal
|first1=Jacob
|last2=Phillips
|first2=Andrew
|last3=Densmore
|first3=Douglas
|last4=Cai
|first4=Yizhi
|editor1-first=Heinz
|editor1-last=Koeppl
|editor2-first=Douglas
|editor2-last=Densmore
|editor3-first=Gianluca
|editor3-last=Setti
|editor4-first=Mario
|editor4-last=di Bernardo
|encyclopedia=Design and Analysis of Biomolecular Circuits
|title=High-Level Programming Languages for Biomolecular Systems
|year=2011
|publisher=Springer
|location=New York Dordrecht Heidelberg London
|isbn=978-1-4419-6765-7
|doi=10.1007/978-1-4419-6766-4
|pages=241
}}
⚫
|}</ref>
|}


==References==
==References==

Revision as of 00:16, 10 October 2013

GenoCAD
Initial release30 August 2007 (2007-08-30)
Stable release
2.2.1 / 8 May 2013; 11 years ago (2013-05-08)
Repository
Written inPHP JavaScript C++ MySQL
TypeComputer-Aided Design Bioinformatics
LicenseApache v2.0
Websitegenocad.org

GenoCAD [1] is an open source web application to design protein expression vectors, artificial gene networks and other genetic constructs from functional blocks called parts for genetic engineering using a rule-based methodology.[1]

Engineering of complex systems is often achieved by a bottom up approach and has led to the use of biological parts as building blocks with certain functions and characteristics and hence GenoCAD is also considered a Computer Assisted Design (CAD) application for synthetic biology. GenoCAD therefore provides a flexible system to manage libraries of public and user-defined genetic parts, a formal design strategy to guide users in the design, a simulation engine (COPASI) to study the behaviour and a customizable user workspace.[1]

History

One difficulty in synthetic biology is that a genetic construct must meet certain constraints in order to be functional. GenoCAD originated as an offshoot of an attempt to formalise these constraints using the theory of formal languages. In 2007, the website www.genocad.org was set up as a proof of concept by researchers at Virginia Bioinformatics Institute, Virginia Tech. Using the website, users could design genes by repeatedly replacing high level genetic constructs with lower level genetic constructs, and eventually with actual DNA sequences.[2]

GenoCAD continues to be developed by Peccoud Lab, a research organisation run by Jean Peccoud, one of the authors of the originating study (A syntactic model to design and verify synthetic genetic constructs derived from standard biological parts, Cai et. al., 2007). On August 31, 2009 , the National Science Foundation granted a three-year $1,421,725 grant to Peccoud, an associate professor at the Virginia Bioinformatics Institute at Virginia Tech, for the development of GenoCAD. [3]

Source code for GenoCAD was released on Sourceforge in December 2009[4] , where it continues to be maintained.

GenoCAD version 2.0 was released in November 2011 and included the ability to simulate the behaviour of the designed genetic code. This feature was a result of a collaboration with the team behind COPASI[5]

Goals

The four aims of the project are to develop a: [6]

  1. computer language to represent the structure of synthetic DNA molecules used in E.coli, yeast, mice, and Arabidopsis thaliana cells
  2. compiler capable of translating DNA sequences into mathematical models in order to predict the encoded phenotype
  3. collaborative workflow environment which allow to share parts, designs, fabrication resource
  4. and to forward the results to the user community through an external advisory board, an annual user conference, and outreach to industry

Features

The main features of GenoCAD can be organized into four main categories. [7] [8]

Workflow of GenoCAD from Virginia Tech
  • Management of genetic sequences: The purpose of this group of features is to help users identify, within large collections of genetic parts, the parts needed for a project and to organize them in project-specific libraries.
    • Genetic parts: Parts have a unique identifier, a name and a more general description. They also have a DNA sequence. Parts are associated with a grammar and assigned to a parts category such a promoter, gene, etc.
    • Parts libraries: Collections of parts are organized in libraries. In some cases part libraries correspond to parts imported from a single source such as another sequence database. In other cases, libraries correspond to the parts used for a particular design project. Parts can be moved from one library to another through a temporary storage area called the cart (analogous to e-commerce shopping carts).
    • Searching parts: Users can search the parts database using the Lucene search engine. Basic and advanced search modes are available. Users can develop complex queries and save them for future reuse.
    • Importing/Exporting parts: Parts can be imported and exported individually or as entire libraries using standard file formats (e.g., tab delimited, FASTA).
  • Combining sequences into genetic constructs: The purpose of this group of features is to streamline the process of combining genetic parts into designs compliant with a specific design strategy.
    • Point-and-click design tool: This wizard guides the user through a series of design decisions that determine the design structure and the selection of parts included in the design.
    • Design management: Designs can be saved in the user workspace. Design statuses are regularly updated to warn users of the consequences of editing parts on previously saved designs.
    • Exporting designs: Designs can be exported using standard file formats (e.g., GenBank, tab delimited, FASTA).
  • Simulate a genetic construct to study its behaviour: GenoCAD supports the COPASI simulation engine. To simulate any design it must be created with an attribute grammar.[9]
  • User workspace: Users can personalize their workspace by adding parts to the GenoCAD database, creating specialized libraries corresponding to specific design projects, and saving designs at different stages of development.

Theoretical foundation

GenoCAD is rooted in the theory of formal languages. In particular, the design rules describing how to combine different kinds of parts form context-free grammars. [10]

The basic concept of Design in GenoCAD is similar to grammar in a language where building a meaningful sentence needs words like subjects, predicates indirect objects etc. and a grammar to put them together. If the gramma fails no meaningful sentence will be generated. Parts can be understood as the words that form a construct like a sentence, which is called design, according to the framework provided by the rules in the grammar. In GenoCAD a design strategy (grammar) needs rules to define which classes of parts (categories) can built a DNA sequence and in what order (e.g. an E. coli gene expression cassette requires: a Promoter, a Ribosome Binding Site (RBS), a Gene and a Terminator).[7]

File:GenoCAD data model.png
In more detail each grammar has a set of rules which defines also the category of parts which are available to build a design. Besides of the public library user libraries can be created and contain public parts as well as user-created parts (Library 1 contains both, Library 2 only user-created parts). The parts for a design must be contained in a single library [1]


Alternatives

The most common alternatives to GenoCAD are Proto, GEC and EuGene[11]

Tool Advantages Disadvantages
GEC
  • Supports SBML[12]
  • Designer only needs to know basic part types and determine constraints [13]
EuGene
  • Interfacing with other simulation and assembly tools[11]
Proto
  • Supports SBML[11]
  • Choice of molecules and sequences can be made by other programs[11]
  • Integration capability with some other languages[11]
  • Relatively hard to learn [11]
  • Results are less efficient [15]

References

  1. ^ a b c d Czar MJ, Cai Y, Peccoud J (2009). "Writing DNA with GenoCAD". Nucleic Acids Res. 37 (web server): W40-7. doi:10.1093/nar/gkp361. PMC 2703884. PMID 19429897.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Cai, Y., Hartnett, B., Gustafsson, C., & Peccoud, J. (2007). A syntactic model to design and verify synthetic genetic constructs derived from standard biological parts. Bioinformatics, 23(20), 2760-2767.
  3. ^ Jodi Lewis (September 14, 2009). "National Science Foundation awards $1.4 million for GenoCAD development". Retrieved October 7, 2013.
  4. ^ Sourceforge http://sourceforge.net/p/genocad/code/commit_browser. Retrieved 8 October 2013. {{cite web}}: Missing or empty |title= (help)
  5. ^ Wilson, Mandy. "GenoCAD Release Notes". Peccoud Lab. Retrieved 8 October 2013.
  6. ^ Jean Peccoud (June 21, 2013). "GenoCAD: Computer Assisted Design of Synthetic DNA". Retrieved October 7, 2013.
  7. ^ a b Wilson ML, Hertzberg R, Adam L, Peccoud J. (2011). "A step-by-step introduction to rule-based design of synthetic genetic constructs using GenoCAD". Methods Enzymol. 498: 173–88. PMID 21601678.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Jean Peccoud (December 8, 2011). "Releasing GenoCAD v2.0". Retrieved October 7, 2013.
  9. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1371/journal.pcbi.1000529, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1371/journal.pcbi.1000529 instead.
  10. ^ Cai Y, Hartnett B, Gustafsson C, Peccoud J. (2007). "A syntactic model to design and verify synthetic genetic constructs derived from standard biological parts". Bioinformatics. 23 (20): 2760–7. doi:10.1093/bioinformatics/btm446. PMID 17804435.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ a b c d e f g h Habibi, N., Mohd Hashim, S. Z., Rodriguez, C. A., & Samian, M. R. (2013). A Review of CADs, Languages and Data Models for Synthetic Biology. Jurnal Teknologi, 63(1).
  12. ^ Marchisio, M. A., & Stelling, J. (2009). Computational design tools for synthetic biology. Current opinion in biotechnology, 20(4), 479-485.
  13. ^ Habibi, N., Mohd Hashim, S. Z., Rodriguez, C. A., & Samian, M. R. (2013). A Review of CADs, Languages and Data Models for Synthetic Biology. Jurnal Teknologi, 63(1).
  14. ^ Pedersen, M. (2010). Modular languages for systems and synthetic biology.
  15. ^ Beal, Jacob; Phillips, Andrew; Densmore, Douglas; Cai, Yizhi (2011). "High-Level Programming Languages for Biomolecular Systems". In Koeppl, Heinz; Densmore, Douglas; Setti, Gianluca; di Bernardo, Mario (eds.). Design and Analysis of Biomolecular Circuits. New York Dordrecht Heidelberg London: Springer. p. 241. doi:10.1007/978-1-4419-6766-4. ISBN 978-1-4419-6765-7. |}
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