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Two-stage designs for experiments with a large number of hypotheses

机译:两阶段设计,可进行大量假设的实验

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Motivation: When a large number of hypotheses are investigated the false discovery rate (FDR) is commonly applied in gene expression analysis or gene association studies. Conventional single-stage designs may lack power due to low sample sizes for the individual hypotheses. We propose two-stage designs where the first stage is used to screen the 'promising' hypotheses which are further investigated at the second stage with an increased sample size. A multiple test procedure based on sequential individual P-values is proposed to control the FDR for the case of independent normal distributions with known variance. Results: The power of optimal two-stage designs is impressively larger than the power of the corresponding single-stage design with equal costs. Extensions to the case of unknown variances and correlated test statistics are investigated by simulations. Moreover, it is shown that the simple multiple test procedure using first stage data for screening purposes and deriving the test decisions only from second stage data is a very powerful option.
机译:动机:研究大量假设时,错误发现率(FDR)通常用于基因表达分析或基因关联研究。由于单个假设的样本量较小,常规的单阶段设计可能会缺乏功能。我们提出了两个阶段的设计,其中第一阶段用于筛选“有前途的”假设,第二阶段将在样本增加的情况下进行进一步研究。提出了一种基于顺序单个P值的多重测试程序,以控制具有已知方差的独立正态分布的情况下的FDR。结果:最优的两阶段设计的功能比同等成本的单阶段设计的功能大得多。通过模拟研究了方差未知情况和相关检验统计量的扩展。此外,已表明,使用第一阶段数据进行筛选并仅从第二阶段数据得出测试决策的简单多次测试程序是一个非常强大的选择。

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