OptCircuit: an optimization based method for computational design of genetic circuits.
OptCircuit: an optimization based method for computational design of genetic circuits.
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DOI：
10.1186/1752-0509-2-24
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发表时间：
2008-03-03
影响因子：
--
通讯作者：
Maranas CD
中科院分区：
文献类型：
--
作者：
Dasika MS;Maranas CD
近年来，越来越多的研究表明，构建简单的合成遗传电路，表现出所需的性能，如振荡行为，诱导剂特定的激活/抑制等，它已被广泛承认，该任务的建设电路，以满足多个诱导剂特定的要求是一个具有挑战性的。这是因为组件交互的描述不完整，而且可以选择和互连组件的方式的数量随着组件的数量呈指数级增加。在本文中，我们将介绍OptCircuit，一个基于优化的框架，自动识别电路组件从列表和连接，带来了所需的功能。多个文献来源被用来编译一个全面的汇编动力学描述的启动子-蛋白质对。目前，使用确定性常微分方程来模拟遗传电路的元素之间的相互作用的动力学，但框架是一般的，足以容纳随机模拟。期望的电路响应被抽象为适当构造的目标函数的最大化/最小化。一个拨动开关的例子的计算结果表明，该框架的能力，以产生不同的复杂性，表现出所需的响应的电路设计的完整列表。为基因解码器确定的设计突出了OptCircuit建议电路配置的能力，这些电路配置超出了与基于数字逻辑的设计原则兼容的电路配置。最后，从浓度带检测器的例子中得到的结果表明，OptCircuit设计电路的能力，其响应取决于外部诱导剂的水平，以及精确的参数进行修改，以纠正现有的（非功能性的）生物电路和恢复功能。我们的研究结果表明，OptCircuit框架可以作为一个设计平台，以帮助集成生物电路的建设和微调。
Recent years has witnessed an increasing number of studies on constructing simple synthetic genetic circuits that exhibit desired properties such as oscillatory behavior, inducer specific activation/repression, etc. It has been widely acknowledged that that task of building circuits to meet multiple inducer-specific requirements is a challenging one. This is because of the incomplete description of component interactions compounded by the fact that the number of ways in which one can chose and interconnect components, increases exponentially with the number of components. In this paper we introduce OptCircuit, an optimization based framework that automatically identifies the circuit components from a list and connectivity that brings about the desired functionality. Multiple literature sources are used to compile a comprehensive compilation of kinetic descriptions of promoter-protein pairs. The dynamics that govern the interactions between the elements of the genetic circuit are currently modeled using deterministic ordinary differential equations but the framework is general enough to accommodate stochastic simulations. The desired circuit response is abstracted as the maximization/minimization of an appropriately constructed objective function. Computational results for a toggle switch example demonstrate the ability of the framework to generate the complete list of circuit designs of varying complexity that exhibit the desired response. Designs identified for a genetic decoder highlight the ability of OptCircuit to suggest circuit configurations that go beyond the ones compatible with digital logic-based design principles. Finally, the results obtained from the concentration band detector example demonstrate the ability of OptCircuit to design circuits whose responses are contingent on the level of external inducer as well as pinpoint parameters for modification to rectify an existing (non-functional) biological circuit and restore functionality. Our results demonstrate that OptCircuit framework can serve as a design platform to aid in the construction and finetuning of integrated biological circuits.
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影响因子：
64.8
作者：
Becskei, A;Serrano, L
通讯作者：
Serrano, L
影响因子：
4.3
作者：
Bansal, V;Sakizlis, V;Pistikopoulos, EN
通讯作者：
Pistikopoulos, EN
影响因子：
2.9
作者：
Hasty, J;Isaacs, F;Collins, JJ
通讯作者：
Collins, JJ
DOI：
10.1073/pnas.040411297
发表时间：
2000-02-29
影响因子：
11.1
作者：
Hasty, J;Pradines, J;Collins, JJ
通讯作者：
Collins, JJ
DOI：
10.1073/pnas.0408507102
发表时间：
2005-03-08
影响因子：
11.1
作者：
Hooshangi, S;Thiberge, S;Weiss, R
通讯作者：
Weiss, R