Xu Zongli, Langie Sabine A S, De Boever Patrick, Taylor Jack A, Niu Liang
Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
Environmental Risk and Health unit, Flemish Institute for Technological Research (VITO), Mol, Belgium.
BMC Genomics. 2017 Jan 3;18(1):4. doi: 10.1186/s12864-016-3426-3.
The Illumina Infinium HumanMethylation450 BeadChip and its successor, Infinium MethylationEPIC BeadChip, have been extensively utilized in epigenome-wide association studies. Both arrays use two fluorescent dyes (Cy3-green/Cy5-red) to measure methylation level at CpG sites. However, performance difference between dyes can result in biased estimates of methylation levels.
Here we describe a novel method, called REgression on Logarithm of Internal Control probes (RELIC) to correct for dye bias on whole array by utilizing the intensity values of paired internal control probes that monitor the two color channels. We evaluate the method in several datasets against other widely used dye-bias correction methods. Results on data quality improvement showed that RELIC correction statistically significantly outperforms alternative dye-bias correction methods. We incorporated the method into the R package ENmix, which is freely available from the Bioconductor website ( https://www.bioconductor.org/packages/release/bioc/html/ENmix.html ).
RELIC is an efficient and robust method to correct for dye-bias in Illumina Methylation BeadChip data. It outperforms other alternative methods and conveniently implemented in R package ENmix to facilitate DNA methylation studies.
Illumina Infinium HumanMethylation450 芯片及其后续产品 Infinium MethylationEPIC 芯片已广泛应用于全表观基因组关联研究。这两种芯片均使用两种荧光染料（Cy3 - 绿色/Cy5 - 红色）来测量 CpG 位点的甲基化水平。然而，染料之间的性能差异可能导致甲基化水平的估计出现偏差。
在此，我们描述了一种名为内部控制探针对数回归（RELIC）的新方法，该方法通过利用监测两个颜色通道的配对内部控制探针的强度值来校正全芯片上的染料偏差。我们在几个数据集中将该方法与其他广泛使用的染料偏差校正方法进行了评估。数据质量改进结果表明，RELIC 校正在统计学上显著优于其他替代的染料偏差校正方法。我们将该方法纳入了 R 包 ENmix 中，该包可从 Bioconductor 网站（https://www.bioconductor.org/packages/release/bioc/html/ENmix.html）免费获取。
RELIC 是一种校正 Illumina 甲基化芯片数据中染料偏差的高效且稳健的方法。它优于其他替代方法，并方便地在 R 包 ENmix 中实现，以促进 DNA 甲基化研究。
