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高维基因组数据的一般功效和样本量计算

General power and sample size calculations for high-dimensional genomic data.

作者信息

van Iterson Maarten, van de Wiel Mark A, Boer Judith M, de Menezes Renée X

机构信息

Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Stat Appl Genet Mol Biol. 2013 Aug;12(4):449-67. doi: 10.1515/sagmb-2012-0046.

Abstract

In the design of microarray or next-generation sequencing experiments it is crucial to choose the appropriate number of biological replicates. As often the number of differentially expressed genes and their effect sizes are small and too few replicates will lead to insufficient power to detect these. On the other hand, too many replicates unnecessary leads to high experimental costs. Power and sample size analysis can guide experimentalist in choosing the appropriate number of biological replicates. Several methods for power and sample size analysis have recently been proposed for microarray data. However, most of these are restricted to two group comparisons and require user-defined effect sizes. Here we propose a pilot-data based method for power and sample size analysis which can handle more general experimental designs and uses pilot-data to obtain estimates of the effect sizes. The method can also handle χ2 distributed test statistics which enables power and sample size calculations for a much wider class of models, including high-dimensional generalized linear models which are used, e.g., for RNA-seq data analysis. The performance of the method is evaluated using simulated and experimental data from several microarray and next-generation sequencing experiments. Furthermore, we compare our proposed method for estimation of the density of effect sizes from pilot data with a recent proposed method specific for two group comparisons.

摘要

在微阵列或下一代测序实验的设计中,选择合适数量的生物学重复至关重要。因为通常差异表达基因的数量及其效应大小都很小,重复次数太少会导致检测这些基因的能力不足。另一方面,过多的重复会不必要地导致高昂的实验成本。功效和样本量分析可以指导实验人员选择合适数量的生物学重复。最近针对微阵列数据提出了几种功效和样本量分析方法。然而,其中大多数方法仅限于两组比较,并且需要用户定义效应大小。在此,我们提出一种基于预实验数据的功效和样本量分析方法,该方法可以处理更一般的实验设计,并使用预实验数据来获得效应大小的估计值。该方法还可以处理χ2分布的检验统计量,从而能够对更广泛的模型进行功效和样本量计算,包括例如用于RNA测序数据分析的高维广义线性模型。使用来自多个微阵列和下一代测序实验的模拟数据和实验数据对该方法的性能进行了评估。此外,我们将我们提出的从预实验数据估计效应大小密度的方法与最近提出的专门用于两组比较的方法进行了比较。

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