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Multiple Comparisons in Microarray Data Analysis

机译:微阵列数据分析中的多重比较

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摘要

Multiplicity is a challenging statistical issue in drug discovery, and a particular example is microarray study. The traditional approach of controlling of the family-wise error rate (FWER) is conservative when the number of tests is large. A more appropriate approach is to control the false discovery rate (FDR). Since the development of the Benjamini and Hochberg (BH) FDR procedure in 1995, many modifications have been proposed aimed at relaxing the requirement for independent test statistics or improving the power of the BH FDR procedure. Comparisons of these procedures in the current literature are not comprehensive and the conclusions on performances are inconsistent. The objectives of this article are three-fold: (a) to perform a more comprehensive comparison of extant multiple testing procedures using two real microarray datasets and various simulated data sets; (b) to explore potential reasons for the inconsistencies in published simulation results; and (c) to identify suitable FDR procedures under different scenarios according to covariance structure, percent of true null hypotheses among multiple tests, and sample size.
机译:多样性是药物发现中一个具有挑战性的统计问题,一个特殊的例子是微阵列研究。当测试数量很多时,传统的控制家庭错误率(FWER)的方法是保守的。一种更合适的方法是控制错误发现率(FDR)。自从1995年开发Benjamini和Hochberg(BH)FDR程序以来,已经提出了许多修改措施,旨在放宽对独立测试统计数据的要求或提高BH FDR程序的功能。当前文献对这些程序的比较尚不全面,有关性能的结论也不一致。本文的目标包括三个方面:(a)使用两个真实的微阵列数据集和各种模拟的数据集对现有的多种测试程序进行更全面的比较; (b)探索导致已发布的模拟结果不一致的潜在原因; (c)根据协方差结构,多重检验中真实无效假设的百分比以及样本量,确定在不同情况下合适的FDR程序。

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