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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reverse engineering gene networks: Integrating genetic perturbations with dynamical modeling
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Reverse engineering gene networks: Integrating genetic perturbations with dynamical modeling

机译：逆向工程基因网络：将遗传扰动与动力学建模相结合

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摘要

While the fundamental building blocks of biology are being tabulated by the various genome projects, microarray technology is setting the stage for the task of deducing the connectivity of large-scale gene networks. We show how the perturbation of carefully chosen genes in a microarray experiment can be used in conjunction with a reverse engineering algorithm to reveal the architecture of an underlying gene regulatory network. Our iterative scheme identifies the network topology by analyzing the steady-state changes in gene expression resulting from the systematic perturbation of a particular node in the network. We highlight the validity of our reverse engineering approach through the successful deduction of the topology of a linear in numero gene network and a recently reported model for the segmentation polarity network in Drosophila melanogaster. Our method may prove useful in identifying and validating specific drug targets and in deconvolving the effects of chemical compounds.
机译：尽管各种基因组计划都在列出生物学的基本构成要素，但微阵列技术正在为演绎大规模基因网络的连通性奠定基础。我们展示了如何在微阵列实验中精心选择的基因的扰动可以与逆向工程算法结合使用，以揭示潜在的基因调控网络的体系结构。我们的迭代方案通过分析基因表达的稳态变化（由网络中特定节点的系统扰动引起）来识别网络拓扑。我们通过成功推导线性分子数字网络的拓扑结构和最近报道的果蝇分段极性网络模型来突出我们逆向工程方法的有效性。我们的方法可能被证明可用于识别和验证特定的药物靶标以及消除化学化合物的影响。

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