Xiong Momiao, Li Jun, Fang Xiangzhong
Human Genetics Center, University of Texas, Houston Health Science Center, TX 77030, USA.
Genetics. 2004 Feb;166(2):1037-52. doi: 10.1534/genetics.166.2.1037.
In this report, we propose the use of structural equations as a tool for identifying and modeling genetic networks and genetic algorithms for searching the most likely genetic networks that best fit the data. After genetic networks are identified, it is fundamental to identify those networks influencing cell phenotypes. To accomplish this task we extend the concept of differential expression of the genes, widely used in gene expression data analysis, to genetic networks. We propose a definition for the differential expression of a genetic network and use the generalized T2 statistic to measure the ability of genetic networks to distinguish different phenotypes. However, describing the differential expression of genetic networks is not enough for understanding biological systems because differences in the expression of genetic networks do not directly reflect regulatory strength between gene activities. Therefore, in this report we also introduce the concept of differentially regulated genetic networks, which has the potential to assess changes of gene regulation in response to perturbation in the environment and may provide new insights into the mechanism of diseases and biological processes. We propose five novel statistics to measure the differences in regulation of genetic networks. To illustrate the concepts and methods for reconstruction of genetic networks and identification of association of genetic networks with function, we applied the proposed models and algorithms to three data sets.
在本报告中,我们建议使用结构方程作为识别和构建遗传网络的工具,并使用遗传算法搜索最能拟合数据的最可能的遗传网络。在识别出遗传网络后,识别那些影响细胞表型的网络至关重要。为完成这项任务,我们将基因表达数据分析中广泛使用的基因差异表达概念扩展到遗传网络。我们提出了遗传网络差异表达的定义,并使用广义T2统计量来衡量遗传网络区分不同表型的能力。然而,描述遗传网络的差异表达对于理解生物系统是不够的,因为遗传网络表达的差异并不能直接反映基因活动之间的调控强度。因此,在本报告中,我们还引入了差异调控遗传网络的概念,它有可能评估基因调控对环境扰动的响应变化,并可能为疾病机制和生物过程提供新的见解。我们提出了五个新的统计量来衡量遗传网络调控的差异。为了说明遗传网络重建以及遗传网络与功能关联识别的概念和方法,我们将所提出的模型和算法应用于三个数据集。