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Modeling Structure-Function Relationships in Synthetic DNA Sequences using Attribute Grammars

机译:使用属性语法在合成DNA序列中建模结构-功能关系

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摘要

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.
机译:认识到某些生物学功能可以与特定的DNA序列相关联,导致生物学的各个领域都采用了遗传部分的概念。这个概念提供了比传统基因概念更好的粒度级别。但是,尚未出现正式地将一组零件与功能相关联的方法。合成生物学不仅要求这种形式主义,而且为测试有关DNA序列与表型之间的关系的假说提供了理想的环境,而这些假说超出了遗传学中使用的以基因为中心的方法。属性语法在计算机科学中用于将程序源代码的文本转换为它表示的计算操作。通过将属性与零件相关联,使用描述DNA序列结构的规则并使用多遍编译过程来修改这些属性的值,可以将DNA序列转换为分子相互作用网络模型。这些功能通过简单的示例语法来说明,这些语法表示基因表达率如何取决于单个或多个部分。通过系统地生成,翻译和模拟由小型遗传零件库生成的设计空间中所有序列的表型,可以验证翻译过程。属性语法代表了一个灵活的框架,将各个部分与生物学功能模型相连接。它们将有助于建立合成的遗传结构文库的数学模型,以表征遗传部分的功能。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程序的开发提供坚实的基础。

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