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合成基因网络的鲁棒性分析与优化

Robustness analysis and tuning of synthetic gene networks.

作者信息

Batt Grégory, Yordanov Boyan, Weiss Ron, Belta Calin

机构信息

Centers for Information and Systems Engineering and for BioDynamics, Boston University, Boston, MA, USA.

出版信息

Bioinformatics. 2007 Sep 15;23(18):2415-22. doi: 10.1093/bioinformatics/btm362. Epub 2007 Jul 27.

Abstract

MOTIVATION

The goal of synthetic biology is to design and construct biological systems that present a desired behavior. The construction of synthetic gene networks implementing simple functions has demonstrated the feasibility of this approach. However, the design of these networks is difficult, notably because existing techniques and tools are not adapted to deal with uncertainties on molecular concentrations and parameter values.

RESULTS

We propose an approach for the analysis of a class of uncertain piecewise-multiaffine differential equation models. This modeling framework is well adapted to the experimental data currently available. Moreover, these models present interesting mathematical properties that allow the development of efficient algorithms for solving robustness analyses and tuning problems. These algorithms are implemented in the tool RoVerGeNe, and their practical applicability and biological relevance are demonstrated on the analysis of the tuning of a synthetic transcriptional cascade built in Escherichia coli.

AVAILABILITY

RoVerGeNe and the transcriptional cascade model are available at http://iasi.bu.edu/%7Ebatt/rovergene/rovergene.htm.

摘要

动机

合成生物学的目标是设计和构建具有期望行为的生物系统。实现简单功能的合成基因网络的构建已证明了这种方法的可行性。然而,这些网络的设计很困难,特别是因为现有技术和工具不适用于处理分子浓度和参数值的不确定性。

结果

我们提出了一种用于分析一类不确定分段多仿射微分方程模型的方法。这种建模框架非常适合当前可用的实验数据。此外,这些模型具有有趣的数学特性,这使得能够开发用于解决鲁棒性分析和调谐问题的高效算法。这些算法在工具RoVerGeNe中实现,并通过对在大肠杆菌中构建的合成转录级联的调谐分析证明了它们的实际适用性和生物学相关性。

可用性

RoVerGeNe和转录级联模型可在http://iasi.bu.edu/%7Ebatt/rovergene/rovergene.htm获得。

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