Chen Min, Xie Yang, Story Michael
Center of Statistical Genomics and Proteomics, Department of Epidemiology and Public Health, Yale University, New Haven, U.S.A.
Commun Stat Theory Methods. 2011 Sep 1;40(17):3055-3069. doi: 10.1080/03610921003797753.
Illumina BeadArrays are becoming an increasingly popular Microarray platform due to its high data quality and relatively low cost. One distinct feature of Illumina BeadArrays is that each array has thousands of negative control bead types containing oligonucleotide sequences that are not specific to any target genes in the genome. This design provides a way of directly estimating the distribution of the background noise. In the literature of background correction for BeadArray data, the information from negative control beads is either ignored, used in a naive way that can lead to a loss in efficiency, or the noise is assumed to be normally distributed. However, we show with real data that the noise can be skewed. In this study we propose an exponential-gamma convolution model for background correction of Illumina BeadArray data. Using both simulated and real data examples, we show that the proposed method can improve the signal estimation and detection of differentially expressed genes when the signal to noise ratio is large and the noise has a skewed distribution.
由于其高数据质量和相对较低的成本,Illumina BeadArrays正成为越来越受欢迎的微阵列平台。Illumina BeadArrays的一个显著特点是,每个阵列都有数千种阴性对照珠类型,包含与基因组中任何目标基因都不特异的寡核苷酸序列。这种设计提供了一种直接估计背景噪声分布的方法。在BeadArray数据的背景校正文献中,来自阴性对照珠的信息要么被忽略,要么以一种可能导致效率损失的简单方式使用,或者假设噪声呈正态分布。然而,我们用实际数据表明,噪声可能是有偏的。在本研究中,我们提出了一种指数-伽马卷积模型用于Illumina BeadArray数据的背景校正。通过模拟和实际数据示例,我们表明,当信噪比大且噪声有偏分布时,所提出的方法可以改善信号估计和差异表达基因的检测。