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DNA 甲基化分析在年龄估计模型中的实验室间适应性——问题与解决方案。

Inter-laboratory adaption of age estimation models by DNA methylation analysis-problems and solutions.

机构信息

Institute of Legal Medicine, University Hospital Essen, Hufelandstr 55, 45122, Essen, Germany.

出版信息

Int J Legal Med. 2020 May;134(3):953-961. doi: 10.1007/s00414-020-02263-7. Epub 2020 Feb 14.

DOI:10.1007/s00414-020-02263-7
PMID:32055939
Abstract

In recent years, a lot of age prediction models based on different CpG motives in different cell types were published determining the biological age of a person by DNA methylation. For a general employment of this technique, maybe even as a routine method, the cross-laboratory application of such models has to be examined. Therefore, we tested two different published age prediction models for blood and mouth swab samples with regard to prediction accuracy (Bekaert et al Epigenetics 10:922-930, 2015a; Bekaert et al Forensic Sci Int Genet Suppl Ser 5:e144-e145, 2015b). Both models are based on CpG sites of four genes (ASPA, EDARADD, PDE4-C, and ELOVL2), but with a different combination of CpGs for the two tissue types. A mean absolute difference (MAD) between chronological and predicted age of 9.84 and 8.32 years for blood and buccal swab models could be demonstrated, respectively, which is significantly worse than the published data, probably due to higher DNA methylation variances in some CpGs. By retraining both prediction models, the prediction accuracy could be improved to a MAD of 5.55 and 4.65 years for the renewed blood and buccal swab model, respectively. This study demonstrates the usefulness of effective DNA standards to normalize DNA methylation data for better comparison of study results.

摘要

近年来,许多基于不同细胞类型中不同 CpG 基序的年龄预测模型被发表,通过 DNA 甲基化来确定一个人的生物年龄。为了普遍应用这种技术,甚至可能将其作为一种常规方法,需要检验这种模型在不同实验室之间的应用。因此,我们测试了两个不同的已发表的基于血液和口腔拭子样本的年龄预测模型的预测准确性(Bekaert 等人,《表观遗传学》10:922-930,2015a;Bekaert 等人,《法庭科学国际遗传学补充标准》5:e144-e145,2015b)。这两个模型都是基于四个基因(ASPA、EDARADD、PDE4-C 和 ELOVL2)的 CpG 位点,但两种组织类型的 CpG 组合不同。血液和口腔拭子模型的预测年龄与实际年龄之间的平均绝对差异(MAD)分别为 9.84 年和 8.32 年,这明显差于已发表的数据,这可能是由于某些 CpG 中的 DNA 甲基化变异较高所致。通过重新训练两个预测模型,可以将预测准确性提高到更新后的血液和口腔拭子模型的 MAD 分别为 5.55 年和 4.65 年。这项研究表明,有效的 DNA 标准对于标准化 DNA 甲基化数据的有用性,以便更好地比较研究结果。

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