Cai Yizhi, Lux Matthew W, Adam Laura, Peccoud Jean
Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.
PLoS Comput Biol. 2009 Oct;5(10):e1000529. doi: 10.1371/journal.pcbi.1000529. Epub 2009 Oct 9.
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.
认识到某些生物学功能可能与特定的DNA序列相关联，这使得生物学的各个领域都采用了遗传部件的概念。这个概念比传统的基因概念提供了更精细的粒度级别。然而，一种正式描述一组部件如何与功能相关的方法尚未出现。合成生物学既需要这样一种形式主义，又为测试关于DNA序列与表型之间关系的假设提供了一个理想的环境，而这些假设超出了遗传学中以基因为中心的方法。属性文法在计算机科学中用于将程序源代码文本翻译成它所代表的计算操作。通过将属性与部件相关联，使用描述DNA序列结构的规则修改这些属性的值，并使用多遍编译过程，可以将DNA序列翻译成分子相互作用网络模型。通过表达基因表达率如何依赖于单个或多个部件的简单示例文法来说明这些能力。通过系统地生成、翻译和模拟由一个小的遗传部件库生成的设计空间中所有序列的表型，来验证翻译过程。属性文法代表了一个将部件与生物学功能模型联系起来的灵活框架。它们将有助于构建为表征遗传部件功能而合成的遗传构建体库的数学模型。这种形式主义也有望为合成生物学的计算机辅助设计应用的开发提供坚实的基础。
