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微阵列研究中针对错误发现率控制进行相关性调整的样本量计算。

Sample size calculation with dependence adjustment for FDR-control in microarray studies.

作者信息

Shao Yongzhao, Tseng Chi-Hong

机构信息

Division of Biostatistics, NYU School of Medicine, 650 First Ave., Fifth Floor, New York, NY 10016, USA.

出版信息

Stat Med. 2007 Oct 15;26(23):4219-37. doi: 10.1002/sim.2862.

Abstract

DNA microarrays have been widely used for the purpose of simultaneously monitoring a large number of gene expression levels to identify differentially expressed genes. Statistical methods for the adjustment of multiple testing have been discussed extensively in the literature. An important further challenge is the existence of dependence among test statistics due to reasons such as gene co-regulation. To plan large-scale genomic studies, sample size determination with appropriate adjustment for both multiple testing and potential dependency among test statistics is crucial to avoid an abundance of false-positive results and/or serious lack of power. We introduce a general approach for calculating sample sizes for two-way multiple comparisons in the presence of dependence among test statistics to ensure adequate overall power when the false discovery rates are controlled. The usefulness of the proposed method is demonstrated via numerical studies using both simulated data and real data from a well-known study of leukaemia.

摘要

DNA微阵列已被广泛用于同时监测大量基因的表达水平,以识别差异表达的基因。文献中已广泛讨论了用于多重检验调整的统计方法。一个重要的进一步挑战是,由于基因共调控等原因,检验统计量之间存在相关性。为了规划大规模基因组研究,在多重检验和检验统计量之间的潜在相关性方面进行适当调整来确定样本量,对于避免出现大量假阳性结果和/或严重缺乏检验效能至关重要。我们引入了一种通用方法,用于在检验统计量之间存在相关性的情况下计算双向多重比较的样本量,以便在控制错误发现率时确保足够的总体检验效能。通过使用来自一项著名白血病研究的模拟数据和真实数据进行数值研究,证明了所提出方法的有效性。

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