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从儿童期到老年的常见表观遗传钟。

A common epigenetic clock from childhood to old age.

机构信息

Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain.

Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain.

出版信息

Forensic Sci Int Genet. 2022 Sep;60:102743. doi: 10.1016/j.fsigen.2022.102743. Epub 2022 Jun 25.

Abstract

Forensic age estimation is a DNA intelligence tool that forms an important part of Forensic DNA Phenotyping. Criminal cases with no suspects or with unsuccessful matches in searches on DNA databases; human identification analyses in mass disasters; anthropological studies or legal disputes; all benefit from age estimation to gain investigative leads. Several age prediction models have been developed to date based on DNA methylation. Although different DNA methylation technologies as well as diverse statistical methods have been proposed, most of them are based on blood samples and mainly restricted to adult age ranges. In the current study, we present an extended age prediction model based on 895 evenly distributed Spanish DNA blood samples from 2 to 104 years old. DNA methylation levels were detected using Agena Bioscience EpiTYPER® technology for a total of seven CpG sites located at seven genomic regions: ELOVL2, ASPA, PDE4C, FHL2, CCDC102B, MIR29B2CHG and chr16:85395429 (GRCh38). The accuracy of the age prediction system was tested by comparing three statistical methods: quantile regression (QR), quantile regression neural network (QRNN) and quantile regression support vector machine (QRSVM). The most accurate predictions were obtained when using QRNN or QRSVM (mean absolute prediction error, MAE of ± 3.36 and ± 3.41, respectively). Validation of the models with an independent Spanish testing set (N = 152) provided similar accuracies for both methods (MAE: ± 3.32 and ± 3.45, respectively). The main advantage of using quantile regression statistical tools lies in obtaining age-dependent prediction intervals, fitting the error to the estimated age. An additional analysis of dimensionality reduction shows a direct correlation of increased error and a reduction of correct classifications as the training sample size is reduced. Results indicated that a minimum sample size of six samples per year-of-age covered by the training set is recommended to efficiently capture the most inter-individual variability..

摘要

法医年龄估计是一种 DNA 智能工具,是法医 DNA 表型分析的重要组成部分。在没有嫌疑人的刑事案件或在 DNA 数据库搜索中没有成功匹配的情况下;在大规模灾难中的人类识别分析;人类学研究或法律纠纷;所有这些都受益于年龄估计,以获得调查线索。迄今为止,已经根据 DNA 甲基化开发了几种年龄预测模型。尽管提出了不同的 DNA 甲基化技术和不同的统计方法,但大多数方法都是基于血液样本,主要限于成人年龄范围。在本研究中,我们提出了一个基于 895 个均匀分布的西班牙 DNA 血液样本的扩展年龄预测模型,年龄从 2 岁到 104 岁不等。使用 Agena Bioscience EpiTYPER®技术检测 DNA 甲基化水平,总共检测了七个位于七个基因组区域的 CpG 位点:ELOVL2、ASPA、PDE4C、FHL2、CCDC102B、MIR29B2CHG 和 chr16:85395429(GRCh38)。通过比较三种统计方法:分位数回归(QR)、分位数回归神经网络(QRNN)和分位数回归支持向量机(QRSVM),测试了年龄预测系统的准确性。当使用 QRNN 或 QRSVM 时,获得了最准确的预测(平均绝对预测误差,MAE 分别为±3.36 和±3.41)。使用独立的西班牙测试集(N=152)对模型进行验证,两种方法的准确性相似(MAE:±3.32 和±3.45)。使用分位数回归统计工具的主要优势在于获得与年龄相关的预测区间,使误差适应估计年龄。进一步的降维分析表明,随着训练样本量的减少,错误增加和正确分类减少之间存在直接相关性。结果表明,建议在训练集中每年至少有六个样本,以有效地捕捉最大的个体间变异性。

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