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

TR Number

Date

2012-04-12

Journal Title

Journal ISSN

Volume Title

Publisher

Public Library of Science

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.

Description

Keywords

DNA sequences, Gene expression, Gene regulatory networks, Phenotypes, Programming language semantics, Semantics, Syntax, Synthetic biology

Citation

Cai Y, Lux MW, Adam L, Peccoud J (2009) Modeling Structure-Function Relationships in Synthetic DNA Sequences using Attribute Grammars. PLoS Comput Biol 5(10): e1000529. doi:10.1371/journal.pcbi.1000529