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Weighted Multiple Hypothesis Testing Procedures

机译:加权多重假设检验程序

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摘要

Multiple hypothesis testing is commonly used in genome research such as genome-wide studies and gene expression data analysis (Lin, 2005). The widely used Bonferroni procedure controls the family-wise error rate (FWER) for multiple hypothesis testing, but has limited statistical power as the number of hypotheses tested increases. The power of multiple testing procedures can be increased by using weighted p-values (Genovese et al., 2006). The weights for the p-values can be estimated by using certain prior information. Wasserman and Roeder (2006) described a weighted Bonferroni procedure, which incorporates weighted p-values into the Bonferroni procedure, and Rubin et al. (2006) and Wasserman and Roeder (2006) estimated the optimal weights that maximize the power of the weighted Bonferroni procedure under the assumption that the means of the test statistics in the multiple testing are known (these weights are called optimal Bonferroni weights). This weighted Bonferroni procedure controls FWER and can have higher power than the Bonferroni procedure, especially when the optimal Bonferroni weights are used. To further improve the power of the weighted Bonferroni procedure, first we propose a weighted Šidák procedure that incorporates weighted p-values into the Šidák procedure, and then we estimate the optimal weights that maximize the average power of the weighted Šidák procedure under the assumption that the means of the test statistics in the multiple testing are known (these weights are called optimal Šidák weights). This weighted Šidák procedure can have higher power than the weighted Bonferroni procedure. Second, we develop a generalized sequential (GS) Šidák procedure that incorporates weighted p-values into the sequential Šidák procedure (Scherrer, 1984). This GS Šidák procedure is an extension of and has higher power than the GS Bonferroni procedure of Holm (1979). Finally, under the assumption that the means of the test statistics in the multiple testing are known, we incorporate the optimal Šidák weights and the optimal Bonferroni weights into the GS Šidák procedure and the GS Bonferroni procedure, respectively. Theoretical proof and/or simulation studies show that the GS Šidák procedure can have higher power than the GS Bonferroni procedure when their corresponding optimal weights are used, and that both of these GS procedures can have much higher power than the weighted Šidák and the weighted Bonferroni procedures. All proposed procedures control the FWER well and are useful when prior information is available to estimate the weights.
机译:多重假设检验通常用于基因组研究,例如全基因组研究和基因表达数据分析(Lin,2005)。广泛使用的Bonferroni程序控制多重假设检验的家庭错误率(FWER),但是随着所检验假设数量的增加,统计能力有限。可以通过使用加权p值来提高多种测试过程的功能(Genovese等,2006)。可以通过使用某些先验信息来估计p值的权重。 Wasserman和Roeder(2006)描述了加权Bonferroni程序,该程序将加权p值合并到Bonferroni程序中,Rubin等人(2006)。 (2006)和Wasserman和Roeder(2006)估计了在加权多重Bonferroni程序的功效最大化的最优权重,前提是多重测试中的测试统计方法均已知(这些权重称为最优Bonferroni权重)。这种加权的Bonferroni程序可控制FWER,并且具有比Bonferroni程序更高的功率,尤其是在使用最佳Bonferroni权重时。为了进一步提高加权Bonferroni过程的功效,我们首先提出了一个加权Šidák过程,该过程将加权p值合并到Šidák过程中,然后在以下假设的前提下,估计使加权Šidák过程的平均功效最大化的最佳权重多重测试中测试统计量的平均值是已知的(这些权重称为最佳Šidák权重)。该加权Šidák过程可以具有比加权Bonferroni过程更高的功效。其次,我们开发了一个广义的顺序(GS)Šidák过程,该过程将加权p值合并到顺序Šidák过程中(Scherrer,1984)。 GSŠidák程序是Holm(1979)的GS Bonferroni程序的扩展,并且具有更高的功效。最后,假设多重测试中的测试统计方法是已知的,我们分别将最佳Šidák权重和最佳Bonferroni权重合并到GSŠidák过程和GS Bonferroni过程中。理论证明和/或模拟研究表明,使用相应的最佳权重时,GSŠidák程序可以具有比GS Bonferroni程序更高的功效,并且这两个GS程序都可以具有比加权Šidák和加权的Bonferroni更高的功效。程序。所有建议的程序均能很好地控制FWER,并且在可以获取先验信息估算重量时很有用。

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