BMC Bioinformatics. 2013;14 Suppl 16(Suppl 16):S5. doi: 10.1186/1471-2105-14-S16-S5. Epub 2013 Oct 22.
An increasing number of genetic components are available in several depositories of such components to facilitate synthetic biology research, but picking out those that will allow a designed circuit to achieve the specified function still requires multiple cycles of testing. Here, we addressed this problem by developing a computational pipeline to mathematically simulate a gene circuit for a comprehensive range and combination of the kinetic parameters of the biological components that constitute the gene circuit.
We showed that, using a well-studied transcriptional repression cascade as an example, the sets of kinetic parameters that could produce the specified system dynamics of the gene circuit formed clusters of recurrent combinations, referred to as kinetic motifs, which appear to be associated with both the specific topology and specified dynamics of the circuit. Furthermore, the use of the resulting "handbook" of performance-ranked kinetic motifs in finding suitable circuit components was illustrated in two application scenarios.
These results show that the computational pipeline developed here can provide a rational-based guide to aid in the design and improvement of synthetic gene circuits.
越来越多的遗传元件可在这些元件的多个存储库中获得，以促进合成生物学研究，但要挑选出那些能够使设计的电路实现指定功能的元件，仍然需要多次测试循环。在这里，我们通过开发一个计算管道来解决这个问题，该管道可以对构成基因电路的生物元件的动力学参数进行全面的范围和组合的数学模拟基因电路。
我们表明，使用一个经过充分研究的转录抑制级联作为一个例子，产生基因电路指定系统动力学的动力学参数集形成了反复出现的组合簇，称为动力学基序，这些基序似乎与电路的特定拓扑结构和指定动力学都有关。此外，在两个应用场景中，使用性能排名靠前的动力学基序的结果“手册”来寻找合适的电路元件得到了说明。
这些结果表明，这里开发的计算管道可以为合成基因电路的设计和改进提供基于理性的指导。
