Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany.
J Biotechnol. 2009 Nov;144(3):190-203. doi: 10.1016/j.jbiotec.2009.07.013. Epub 2009 Jul 22.
Reverse engineering of gene networks aims at revealing the structure of the gene regulation network in a biological system by reasoning backward directly from experimental data. Many methods have recently been proposed for reverse engineering of gene networks by using gene transcript expression data measured by microarray. Whereas the potentials of the methods have been well demonstrated, the assumptions and limitations behind them are often not clearly stated or not well understood. In this review, we first briefly explain the principles of the major methods, identify the assumptions behind them and pinpoint the limitations and possible pitfalls in applying them to real biological questions. With regard to applications, we then discuss challenges in the experimental verification of gene networks generated from reverse engineering methods. We further propose an optimal experimental design for allocating sampling schedule and possible strategies for reducing the limitations of some of the current reverse engineering methods. Finally, we examine the perspectives for the development of reverse engineering and urge the need to move from revealing network structure to the dynamics of biological systems.
基因网络的反向工程旨在通过直接从实验数据进行反向推理，揭示生物系统中基因调控网络的结构。最近已经提出了许多使用微阵列测量的基因转录表达数据来反向工程基因网络的方法。虽然这些方法的潜力已经得到了很好的证明，但它们背后的假设和局限性往往没有得到明确说明或没有得到很好的理解。在这篇综述中，我们首先简要解释了主要方法的原理，确定了它们背后的假设，并指出了将它们应用于实际生物学问题的局限性和可能的陷阱。关于应用，我们随后讨论了从反向工程方法生成的基因网络的实验验证中的挑战。我们进一步提出了一种优化的实验设计，用于分配采样计划，并提出了一些可能的策略来减少当前一些反向工程方法的局限性。最后，我们考察了反向工程的发展前景，并敦促从揭示网络结构转向研究生物系统的动态。
