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用于控制微阵列实验中错误发现比例分布的样本量计算。

Sample size calculations for controlling the distribution of false discovery proportion in microarray experiments.

作者信息

Oura Tomonori, Matsui Shigeyuki, Kawakami Koji

机构信息

Department of Biostatistics, Kyoto University School of Public Health, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.

出版信息

Biostatistics. 2009 Oct;10(4):694-705. doi: 10.1093/biostatistics/kxp024. Epub 2009 Jul 23.

Abstract

The false discovery proportion (FDP), the proportion of false rejections among all rejections, provides useful criteria for controlling false positives in multiple testing to detect differential genes in microarray experiments. Owing to a substantial variability in FDP for correlated genes, some authors considered controlling actual FDP, instead of its expectation, that is false discovery rate, in multiple testing. However, there has been no attempt to do this in the design of microarray experiments. In this article, we develop a procedure for sample size calculation to control the distributions of FDP and true positives simultaneously under blockwise correlation structures among genes. The sizes of gene blocks, correlation coefficients, and effect sizes within gene blocks can vary across gene blocks. Gene clustering is proposed to identify gene blocks using historical data sets. The adequacy of the procedure is demonstrated using simulated data sets. An application to a clinical study for lymphoma is also provided.

摘要

错误发现比例(FDP),即所有拒绝中错误拒绝的比例,为在多重检验中控制假阳性以检测微阵列实验中的差异基因提供了有用的标准。由于相关基因的FDP存在很大差异,一些作者考虑在多重检验中控制实际的FDP,而不是其期望值(即错误发现率)。然而,在微阵列实验设计中尚未有人尝试这样做。在本文中,我们开发了一种样本量计算程序,以在基因间的分块相关结构下同时控制FDP和真阳性的分布。基因块的大小、相关系数以及基因块内的效应大小在不同基因块之间可能会有所不同。我们提出了基因聚类方法,利用历史数据集来识别基因块。通过模拟数据集证明了该程序的适用性。此外,还提供了一个在淋巴瘤临床研究中的应用实例。

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