在微阵列实验中鉴定显著差异表达基因的多重测试程序的力量

TAN Yuan-De, YAN Heng-Mei
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引用次数: 1

摘要

由于微阵列实验涉及的高操作成本,在给定的多次测试程序中检测显着差异表达的基因所需的重复次数的确定是相当重要的。计算功率/重复数所需的多个测试程序为微阵列实验提供了设计指导。在此模型的基础上,通过选择多重测试过程,基于置换重采样的表达式噪声可以显著降低。混合分布模型方法适用于从单一噪声源或从多个噪声源获得的各种微阵列数据类型。通过在给定功率的微阵列实验中使用所需的生物重复数,或通过确定检测显著差异表达的基因所需的功率,给定样本量,或可以选择最佳的多重测试方法。以观察到的3 000个脑卒中基因微阵列数据集为例,拟合t统计量的单分布模型,计算了4种常用的多重检测程序检测表达变化基因d的能力。结果表明,在多种检测程序中,b程序检测小变化基因的能力最低,而bh程序检测小变化基因的能力最高。然而,所有的多重测试程序都有相同的能力来识别具有最大变化的基因。与单一测试类似,bh程序检测小变化的能力不随基因数量的增加而变化,但其他三个多重测试程序的能力随着基因数量的增加而下降。
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Powers of Multiple-Testing Procedures for Identification of Genes Significantly Differentially Expressed in Microarray Experiments

Because of the high operation costs involved in microarray experiments, the determination of the number of replicates required to detect a gene significantly differentially expressed in a given multiple-testing procedure is of considerable significance. Calculation of power/replicate numbers required in multiple-testing procedures provides design guidance for microarray experiments. Based on this model and by choice of a multiple-testing procedure, expression noises based on permutation resampling can be considerably minimized. The method for mixture distribution model is suitable to various microarray data types obtained from single noise sources, or from multiple noise sources. By using the biological replicate number required in microarray experiments for a given power or by determining the power required to detect a gene significantly differentially expressed, given the sample size, or the best multiple-testing method can be chosen. As an example, a single-distribution model of t-statistic was fitted to an observed microarray dataset of 3 000 genes responsive to stroke in rat, and then used to calculate powers of four popular multiple-testing procedures to detect a gene of an expression change D. The results show that the B-procedure had the lowest power to detect a gene of small change among the multiple-testing procedures, whereas the BH-procedure had the highest power. However, all multiple-testing procedures had the same power to identify a gene having the largest change. Similar to a single test, the power of the BH-procedure to detect a small change does not vary as the number of genes increases, but powers of the other three multiple-testing procedures decline as the number of genes increases.

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