False discovery rate, sensitivity and sample size for microarray studies
False discovery rate, sensitivity and sample size for microarray studies
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DOI：
10.1093/bioinformatics/bti448
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发表时间：
2005-07-01
期刊：
影响因子：
5.8
通讯作者：
Ploner, A
中科院分区：
文献类型：
--
作者：
Pawitan, Y;Michiels, S;Ploner, A
动机：在微阵列数据研究中，大多数研究人员都敏锐地意识到潜在的高假阳性率和控制它的必要性。一个关键的统计转变是从众所周知的P值转移到假发现率（FDR）。较少的讨论可能已经花在敏感性或相关的假阴性率（FNR）。本文的目的是以简单的方式解释为什么从P值到FDR的转移对于微阵列数据的统计评估是必要的，阐明FDR的决定因素，并且对于双样本比较研究，讨论其在设计阶段通过样本大小的控制。结果：我们使用一个混合模型，涉及差异表达（DE）和非DE基因，抓住了最常见的问题，发现DE基因。确定FDR的因素是（1）真正差异表达基因的比例，（2）真正差异的分布，（3）测量变异性和（4）样本量。目前许多小微阵列研究都受到大FDR的困扰，但单独控制FDR可能导致不可接受的大FNR。在评价微阵列研究的设计时，灵敏度或FNR曲线应与FDR曲线一起进行常规计算。在某些假设下，FDR和FNR曲线重合，从而简化了用于联合控制FDR和FNR的样本量的选择。
Motivation: In microarray data studies most researchers are keenly aware of the potentially high rate of false positives and the need to control it. One key statistical shift is the move away from the well-known P-value to false discovery rate (FDR). Less discussion perhaps has been spent on the sensitivity or the associated false negative rate (FNR). The purpose of this paper is to explain in simple ways why the shift from P-value to FDR for statistical assessment of microarray data is necessary, to elucidate the determining factors of FDR and, for a two-sample comparative study, to discuss its control via sample size at the design stage.Results: We use a mixture model, involving differentially expressed (DE) and non-DE genes, that captures the most common problem of finding DE genes. Factors determining FDR are (1) the proportion of truly differentially expressed genes, (2) the distribution of the true differences, (3) measurement variability and (4) sample size. Many current small microarray studies are plagued with large FDR, but controlling FDR alone can lead to unacceptably large FNR. In evaluating a design of a microarray study, sensitivity or FNR curves should be computed routinely together with FDR curves. Under certain assumptions, the FDR and FNR curves coincide, thus simplifying the choice of sample size for controlling the FDR and FNR jointly.