Yordanov Boyan, Dalchau Neil, Grant Paul K, Pedersen Michael, Emmott Stephen, Haseloff Jim, Phillips Andrew
Microsoft Research, Cambridge CB1 2FB, U.K.
ACS Synth Biol. 2014 Aug 15;3(8):578-88. doi: 10.1021/sb400152n. Epub 2014 Mar 14.
The ability to design and construct synthetic biological systems with predictable behavior could enable significant advances in medical treatment, agricultural sustainability, and bioenergy production. However, to reach a stage where such systems can be reliably designed from biological components, integrated experimental and computational techniques that enable robust component characterization are needed. In this paper we present a computational method for the automated characterization of genetic components. Our method exploits a recently developed multichannel experimental protocol and integrates bacterial growth modeling, Bayesian parameter estimation, and model selection, together with data processing steps that are amenable to automation. We implement the method within the Genetic Engineering of Cells modeling and design environment, which enables both characterization and design to be integrated within a common software framework. To demonstrate the application of the method, we quantitatively characterize a synthetic receiver device that responds to the 3-oxohexanoyl-homoserine lactone signal, across a range of experimental conditions.
设计和构建具有可预测行为的合成生物系统的能力,有望在医学治疗、农业可持续发展和生物能源生产等方面取得重大进展。然而,要达到能够从生物组件可靠地设计此类系统的阶段,就需要集成实验和计算技术,以便对组件进行强有力的表征。在本文中,我们提出了一种用于基因组件自动表征的计算方法。我们的方法利用了最近开发的多通道实验方案,并集成了细菌生长建模、贝叶斯参数估计和模型选择,以及适合自动化的数据处理步骤。我们在细胞基因工程建模与设计环境中实现了该方法,该环境能够将表征和设计集成在一个通用的软件框架内。为了证明该方法的应用,我们在一系列实验条件下,对响应3-氧代己酰高丝氨酸内酯信号的合成受体装置进行了定量表征。