Tan Yuan-De, Fornage Myriam, Fu Yun-Xin
Institute of Molecular Medicine, School of Public Health, University of Texas at Houston, Houston, TX 77030, USA.
Laboratory for Conservation and Utilization of Bioresources, Yunnan University, Kunming, Yunnan 650, China; Human Genetics Center, School of Public Health, University of Texas at Houston, Houston, TX 77030, USA.
Genomics. 2006 Dec;88(6):846-854. doi: 10.1016/j.ygeno.2006.08.003. Epub 2006 Sep 18.
Microarray technology provides a powerful tool for the expression profile of thousands of genes simultaneously, which makes it possible to explore the molecular and metabolic etiology of the development of a complex disease under study. However, classical statistical methods and technologies fail to be applicable to microarray data. Therefore, it is necessary and motivating to develop powerful methods for large-scale statistical analyses. In this paper, we described a novel method, called Ranking Analysis of Microarray Data (RAM). RAM, which is a large-scale two-sample t-test method, is based on comparisons between a set of ranked T statistics and a set of ranked Z values (a set of ranked estimated null scores) yielded by a "randomly splitting" approach instead of a "permutation" approach and a two-simulation strategy for estimating the proportion of genes identified by chance, i.e., the false discovery rate (FDR). The results obtained from the simulated and observed microarray data show that RAM is more efficient in identification of genes differentially expressed and estimation of FDR under undesirable conditions such as a large fudge factor, small sample size, or mixture distribution of noises than Significance Analysis of Microarrays.
微阵列技术为同时分析数千个基因的表达谱提供了一个强大的工具,这使得探索所研究的复杂疾病发生发展的分子和代谢病因成为可能。然而,经典的统计方法和技术并不适用于微阵列数据。因此,开发强大的大规模统计分析方法既必要又具有启发性。在本文中,我们描述了一种名为微阵列数据排序分析(RAM)的新方法。RAM是一种大规模双样本t检验方法,它基于一组排序后的T统计量与通过“随机分割”方法而非“置换”方法产生的一组排序后的Z值(一组排序后的估计零分)之间的比较,以及一种用于估计偶然鉴定出的基因比例(即错误发现率(FDR))的双模拟策略。从模拟和实测微阵列数据获得的结果表明,在诸如较大的调整因子、较小的样本量或噪声混合分布等不利条件下,与微阵列显著性分析相比,RAM在鉴定差异表达基因和估计FDR方面更有效。