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Bioinformatics Advance Access first published online on September 5, 2007
This version published online on September 14, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm446
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

A syntactic model to design and verify synthetic genetic constructs derived from standard biological parts

Yizhi Cai 1, Brian Hartnett 1, Claes Gustafsson 2 and Jean Peccoud 1,*

1Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Washington St, MC 0477, Blacksburg, VA 20061 and 2DNA 2.0 Inc. 430 O'Brien Drive, Suite E Menlo Park, CA 94025

*To whom correspondence should be addressed. Prof. Jean Peccoud, E-mail: peccoud{at}vt.edu


  Abstract

Motivation: The sequence of artificial genetic constructs is composed of multiple functional fragments, or genetic parts, involved in different molecular steps of gene expression mechanisms. Biologists have deciphered structural rules that the design of genetic constructs needs to follow in order to ensure a successful completion of the gene expression process, but these rules have not been formalized, making it challenging for non-specialists to benefit from the recent progress in gene synthesis

Results: We show that context-free grammars (CFG) can formalize these design principles. This approach provides a path to organizing libraries of genetic parts according to their biological functions, which correspond to the syntactic categories of the CFG. It also provides a framework for the systematic design of new genetic constructs consistent with the design principles expressed in the CFG. Using parsing algorithms, this syntactic model enables the verification of existing constructs. We illustrate these possibilities by describing a CFG that generates the most common architectures of genetic constructs in E. coli.

Availability: A web site allows readers to experiment with the algorithms presented in this article: www.genocad.org

Contact: peccoud{at}vt.edu

Supplementary information: Sequences and models can be downloaded from www.genocad.org.

Associate Editor: Prof. John Quackenbush

Received on July 3, 2007; revised on August 20, 2007; accepted on August 21, 2007

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