A Logic Programming Language for Computational Nucleic Acid Devices
A Logic Programming Language for Computational Nucleic Acid Devices
复制标题
DOI：
10.1021/acssynbio.8b00229
复制
发表时间：
2019-07-01
影响因子：
4.7
通讯作者：
Phillips, Andrew
中科院分区：
文献类型：
--
作者：
Spaccasassi, Carlo;Lakin, Matthew R.;Phillips, Andrew
计算核酸设备具有实现广泛的生物技术应用的巨大潜力，包括用于分子生物学研究的智能探针，复杂化合物的体外组装，高精度的体外疾病诊断以及最终在活细胞内的计算疗法。这种应用的多样性得到了一系列实施策略的支持，包括核酸链位移，底物定位以及与聚合酶，Nickase和Exonicleclelease功能的酶使用。但是，现有的计算设计工具无法以统一的方式考虑这些策略。本文介绍了一种逻辑编程语言，该语言允许设计和分析广泛的计算核酸系统。该语言通过新颖的方程理论扩展了标准逻辑编程，以表达核酸分子基序。它会自动识别完整系统中存在的匹配图案，以便应用以逻辑规则表示的指定转换。该语言支持逻辑谓词的定义，这些定义提供了需要满足的约束才能应用给定规则。该语言足以表达具有复杂拓扑结构的核链位移系统的语义以及由广泛酶执行的计算，并且对于新的实施策略而言易于扩展。我们的方法为设计计算核酸设备设计的统一框架奠定了基础。
Computational nucleic acid devices show great potential for enabling a broad range of biotechnology applications, including smart probes for molecular biology research, in vitro assembly of complex compounds, high-precision in vitro disease diagnosis and, ultimately, computational theranostics inside living cells. This diversity of applications is supported by a range of implementation strategies, including nucleic acid strand displacement, localization to substrates, and the use of enzymes with polymerase, nickase, and exonuclease functionality. However, existing computational design tools are unable to account for these strategies in a unified manner. This paper presents a logic programming language that allows a broad range of computational nucleic acid systems to be designed and analyzed. The language extends standard logic programming with a novel equational theory to express nucleic acid molecular motifs. It automatically identifies matching motifs present in the full system, in order to apply a specified transformation expressed as a logical rule. The language supports the definition of logic predicates, which provide constraints that need to be satisfied in order for a given rule to be applied. The language is sufficiently expressive to encode the semantics of nucleic strand displacement systems with complex topologies, together with computation performed by a broad range of enzymes, and is readily extensible to new implementation strategies. Our approach lays the foundation for a unifying framework for the design of computational nucleic acid devices.