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Improving false discovery rate estimation

机译:改善错误发现率估计

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Motivation: Recent attempts to account for multiple testing in the analysis of microarray data have focused on controlling the false discovery rate (FDR). However, rigorous control of the FDR at a preselected level is often impractical. Consequently, it has been suggested to use the q-value as an estimate of the proportion of false discoveries among a set of significant findings. However, such an interpretation of the q-value may be unwarranted considering that the q-value is based on an unstable estimator of the positive FDR (pFDR). Another method proposes estimating the FDR by modeling p-values as arising from a beta-uniform mixture (BUM) distribution. Unfortunately, the BUM approach is reliable only in settings where the assumed model accurately represents the actual distribution of p-values. Methods: A method called the spacings LOESS histogram (SPLOSH) is proposed for estimating the conditional FDR (cFDR), the expected proportion of false positives conditioned on having k ‘significant’ findings. SPLOSH is designed to be more stable than the q-value and applicable in a wider variety of settings than BUM. Results: In a simulation study and data analysis example, SPLOSH exhibits the desired characteristics relative to the q-value and BUM.
机译:动机:最近在微阵列数据分析中考虑多种测试的尝试集中于控制错误发现率(FDR)。但是,将FDR严格控制在预选级别通常是不切实际的。因此,已经建议使用q值作为一组重要发现中虚假发现所占比例的估计。但是,考虑到q值基于正FDR(pFDR)的不稳定估计量,可能无法保证对q值进行这种解释。另一种方法建议通过对源自β均匀混合物(BUM)分布的p值进行建模来估算FDR。不幸的是,BUM方法仅在假定模型准确表示p值实际分布的设置中才是可靠的。方法:提出了一种称为间距LOESS直方图(SPLOSH)的方法,用于估计条件FDR(cFDR),即假阳性的预期比例以k个“显着”发现为条件。 SPLOSH被设计为比q值更稳定,并且可以比BUM应用于更广泛的设置中。结果:在仿真研究和数据分析示例中,SPLOSH表现出相对于q值和BUM的所需特性。

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