Limits...
Modeling structure-function relationships in synthetic DNA sequences using attribute grammars.

Cai Y, Lux MW, Adam L, Peccoud J - PLoS Comput. Biol. (2009)

Bottom Line: Recognizing that certain biological functions can be associated with specific DNA sequences has led various fields of biology to adopt the notion of the genetic part.They will be instrumental for building mathematical models of libraries of genetic constructs synthesized to characterize the function of genetic parts.This formalism is also expected to provide a solid foundation for the development of computer assisted design applications for synthetic biology.

View Article: PubMed Central - PubMed

Affiliation: Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.

ABSTRACT
Recognizing that certain biological functions can be associated with specific DNA sequences has led various fields of biology to adopt the notion of the genetic part. This concept provides a finer level of granularity than the traditional notion of the gene. However, a method of formally relating how a set of parts relates to a function has not yet emerged. Synthetic biology both demands such a formalism and provides an ideal setting for testing hypotheses about relationships between DNA sequences and phenotypes beyond the gene-centric methods used in genetics. Attribute grammars are used in computer science to translate the text of a program source code into the computational operations it represents. By associating attributes with parts, modifying the value of these attributes using rules that describe the structure of DNA sequences, and using a multi-pass compilation process, it is possible to translate DNA sequences into molecular interaction network models. These capabilities are illustrated by simple example grammars expressing how gene expression rates are dependent upon single or multiple parts. The translation process is validated by systematically generating, translating, and simulating the phenotype of all the sequences in the design space generated by a small library of genetic parts. Attribute grammars represent a flexible framework connecting parts with models of biological function. They will be instrumental for building mathematical models of libraries of genetic constructs synthesized to characterize the function of genetic parts. This formalism is also expected to provide a solid foundation for the development of computer assisted design applications for synthetic biology.

Show MeSH
An example of attribute grammar.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2748682&req=5

pcbi-1000529-g003: An example of attribute grammar.

Mentions: We have developed a simple grammar compact enough to be presented extensively, yet sufficiently complex to represent basic epistatic interactions. The grammar generates constructs composed of one or more gene expression cassettes. The gene expression cassettes are themselves composed of a promoter, cistron, and transcription terminator. Finally, a cistron is composed of a Ribosome Binding Site (RBS) and a coding sequence (gene). The syntax is composed of 12 production rules (P1 to P12) displayed in bold characters in Figure 3 where each entry is composed of a rewriting rule (bold), and semantic actions (curly brackets). The symbol ε refers to an empty string, [ , ] to a list, [] to an empty list, and the ‘+’ sign indicates the concatenation operation on two lists. This syntax is comparable to the one described previously [50] except that we introduced the extra non-terminal restConstructs to allow the generation of constructs with multiple cassettes without introducing parsing problems due to direct left recursions [61].


Modeling structure-function relationships in synthetic DNA sequences using attribute grammars.

Cai Y, Lux MW, Adam L, Peccoud J - PLoS Comput. Biol. (2009)

An example of attribute grammar.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2748682&req=5

pcbi-1000529-g003: An example of attribute grammar.
Mentions: We have developed a simple grammar compact enough to be presented extensively, yet sufficiently complex to represent basic epistatic interactions. The grammar generates constructs composed of one or more gene expression cassettes. The gene expression cassettes are themselves composed of a promoter, cistron, and transcription terminator. Finally, a cistron is composed of a Ribosome Binding Site (RBS) and a coding sequence (gene). The syntax is composed of 12 production rules (P1 to P12) displayed in bold characters in Figure 3 where each entry is composed of a rewriting rule (bold), and semantic actions (curly brackets). The symbol ε refers to an empty string, [ , ] to a list, [] to an empty list, and the ‘+’ sign indicates the concatenation operation on two lists. This syntax is comparable to the one described previously [50] except that we introduced the extra non-terminal restConstructs to allow the generation of constructs with multiple cassettes without introducing parsing problems due to direct left recursions [61].

Bottom Line: Recognizing that certain biological functions can be associated with specific DNA sequences has led various fields of biology to adopt the notion of the genetic part.They will be instrumental for building mathematical models of libraries of genetic constructs synthesized to characterize the function of genetic parts.This formalism is also expected to provide a solid foundation for the development of computer assisted design applications for synthetic biology.

View Article: PubMed Central - PubMed

Affiliation: Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.

ABSTRACT
Recognizing that certain biological functions can be associated with specific DNA sequences has led various fields of biology to adopt the notion of the genetic part. This concept provides a finer level of granularity than the traditional notion of the gene. However, a method of formally relating how a set of parts relates to a function has not yet emerged. Synthetic biology both demands such a formalism and provides an ideal setting for testing hypotheses about relationships between DNA sequences and phenotypes beyond the gene-centric methods used in genetics. Attribute grammars are used in computer science to translate the text of a program source code into the computational operations it represents. By associating attributes with parts, modifying the value of these attributes using rules that describe the structure of DNA sequences, and using a multi-pass compilation process, it is possible to translate DNA sequences into molecular interaction network models. These capabilities are illustrated by simple example grammars expressing how gene expression rates are dependent upon single or multiple parts. The translation process is validated by systematically generating, translating, and simulating the phenotype of all the sequences in the design space generated by a small library of genetic parts. Attribute grammars represent a flexible framework connecting parts with models of biological function. They will be instrumental for building mathematical models of libraries of genetic constructs synthesized to characterize the function of genetic parts. This formalism is also expected to provide a solid foundation for the development of computer assisted design applications for synthetic biology.

Show MeSH