Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes.
Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes.
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DOI：
10.1093/nar/gkw967
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发表时间：
2017-02-28
影响因子：
14.9
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
Zhou W;Laird PW;Shen H
Illumina Infinium DNA甲基化珠子芯片代表了最广泛使用的基因组级DNA甲基化分析。现有的掩盖Infinium探针重叠重复或单核苷酸多态性（snp）的策略在很大程度上是基于特别的假设和主观标准。此外，最近推出的MethylationEPIC （EPIC）阵列扩展了该平台的实用性，但尚未得到很好的表征。我们在本文中对EPIC和HM450微阵列上的探针进行了广泛的表征，包括对最新基因组构建的可映射性，3΄嵌套子序列的基因组拷贝数以及多态性的影响，包括I型探针先前未被识别的颜色通道开关。我们展示了对表现不佳的探针的排除标准的经验证据，提供了比目前的临时排除标准更健全的基础。此外，我们还描述了新的探针用途，例如在EPIC阵列上现有的59个显式SNP探针的基础上增加了1052个SNP探针，并使用这些探针来预测种族。最后，我们提出了一种创新的带外彩色通道应用，用于双重使用62 371探针作为内部亚硫酸氢盐转换控制。
Illumina Infinium DNA Methylation BeadChips represent the most widely used genome-scale DNA methylation assays. Existing strategies for masking Infinium probes overlapping repeats or single nucleotide polymorphisms (SNPs) are based largely on ad hoc assumptions and subjective criteria. In addition, the recently introduced MethylationEPIC (EPIC) array expands on the utility of this platform, but has not yet been well characterized. We present in this paper an extensive characterization of probes on the EPIC and HM450 microarrays, including mappability to the latest genome build, genomic copy number of the 3΄ nested subsequence and influence of polymorphisms including a previously unrecognized color channel switch for Type I probes. We show empirical evidence for exclusion criteria for underperforming probes, providing a sounder basis than current ad hoc criteria for exclusion. In addition, we describe novel probe uses, exemplified by the addition of a total of 1052 SNP probes to the existing 59 explicit SNP probes on the EPIC array and the use of these probes to predict ethnicity. Finally, we present an innovative out-of-band color channel application for the dual use of 62 371 probes as internal bisulfite conversion controls.