Recent technological and methodological developments have enabled the use of array-based DNA methylation data to call copy number variants (CNVs). ChAMP, Conumee, and cnAnalysis450k are popular methods currently used to call CNVs using methylation data. However, so far, no studies have analyzed the reliability of these methods using real samples. Data from a cohort of individuals with genotype and DNA methylation data generated using the HumanMethylation450 and MethylationEPIC BeadChips were used to assess the consistency between the CNV calls generated by methylation and genotype data. We also took advantage of repeated measures of methylation data collected from the same individuals to compare the reliability of CNVs called by ChAMP, Conumee, and cnAnalysis450k for both the methylation arrays. ChAMP identified more CNVs than Conumee and cnAnalysis450k for both the arrays and, as a consequence, had a higher overlap (~62%) with the calls from the genotype data. However, all methods had relatively low reliability. For the MethylationEPIC array, Conumee had the highest reliability (57.6%), whereas for the HumanMethylation450 array, cnAnalysis450k had the highest reliability (43.0%). Overall, the MethylationEPIC array provided significant gains in reliability for CNV calling over the HumanMethylation450 array but not for overlap with CNVs called using genotype data.

中文翻译：

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使用 DNA 甲基化的拷贝数变异调用方法的关键评估。

最近的技术和方法发展使基于阵列的 DNA 甲基化数据能够调用拷贝数变异 (CNV)。ChAMP、Conumee 和 cnAnalysis450k 是目前使用甲基化数据调用 CNV 的流行方法。然而，到目前为止，还没有研究使用真实样本分析这些方法的可靠性。使用 HumanMethylation450 和 MethylationEPIC BeadChip 生成的具有基因型和 DNA 甲基化数据的一组个体的数据用于评估甲基化和基因型数据生成的 CNV 调用之间的一致性。我们还利用重复测量从同一个人收集的甲基化数据来比较 ChAMP、Conumee 和 cnAnalysis450k 对两个甲基化阵列调用的 CNV 的可靠性。对于这两个阵列，ChAMP 比 Conumee 和 cnAnalysis450k 识别出更多的 CNV，因此与来自基因型数据的调用具有更高的重叠 (~62%)。然而，所有方法的可靠性都相对较低。对于 MethylationEPIC 阵列，Conumee 具有最高的可靠性 (57.6%)，而对于 HumanMethylation450 阵列，cnAnalysis450k 具有最高的可靠性 (43.0%)。总体而言，MethylationEPIC 阵列为通过 HumanMethylation450 阵列调用的 CNV 提供了显着的可靠性增益，但不与使用基因型数据调用的 CNV 重叠。而对于 HumanMethylation450 阵列，cnAnalysis450k 具有最高的可靠性 (43.0%)。总体而言，MethylationEPIC 阵列为通过 HumanMethylation450 阵列调用的 CNV 提供了显着的可靠性增益，但不与使用基因型数据调用的 CNV 重叠。而对于 HumanMethylation450 阵列，cnAnalysis450k 具有最高的可靠性 (43.0%)。总体而言，MethylationEPIC 阵列为通过 HumanMethylation450 阵列调用的 CNV 提供了显着的可靠性增益，但不与使用基因型数据调用的 CNV 重叠。