小鼠血液中年龄相关的DNA甲基化微单倍型的筛选与验证
Screening and validation of age-related DNA methylation microhaplotypes in mouse blood
田艺博 1吴雨静 1肖君华 1周宇荀 1李凯1
作者信息
- 1. 东华大学生物与医学工程学院,上海 201620
- 折叠
摘要
目的 DNA甲基化微单倍型是指极短范围内多个甲基化位点的组合,其单倍型具有丰富的多样性.筛选和验证小鼠血液中年龄相关的DNA甲基化微单倍型.方法 首先,构建基于小鼠参考基因组的DNA甲基化微单倍型理论数据集.其次,利用网络数据库中小鼠血液DNA甲基化高通量测序信息,采用Spearman秩相关分析方法筛选年龄相关的DNA甲基化微单倍型.最后,以验证数据集交叉验证.结果 小鼠基因组中 50 bp范围内的DNA甲基化微单倍型位点数量共计 6787 142 个,由个位数的 CpG 位点所组成的 DNA 甲基化微单倍型占比98.64%.在 58 个小鼠血液样本中共筛选出 5835 个年龄相关的 DNA甲基化微单倍型(Spearman 秩相关检验,|rho|＞0.5,P＜0.01),在DNA甲基化微单倍型中占 0.086%.最后,在 95 例独立的样本中对具有高相关性的前100 个年龄相关的DNA甲基化微单倍型进行验证,最终得到 44 个位点.结论 本研究筛选出的年龄相关的DNA甲基化微单倍型可以为后续小鼠血液表观年龄预测及衰老研究提供借鉴.
Abstract
Objective The DNA methylation microhaplotype(DMH)refers to the combination of multiple methylation sites within a very short range,and these haplotypes show wide diversity.We carried out screening and validation of age-related DMHs in mouse blood.Methods We initially constructed a theoretical dataset of DMHs based on the mouse reference genome.We then screened age-related DMHs by Spearman's rank correlation analysis,using high-throughput sequencing information for DNA methylation in mouse blood from a network database.Finally,cross-validation was performed using a validation dataset.Results A total of 6787 142 DMH sites were identified within 50 bp in the mouse genome,including 98.64%of single-digit CpG sites.A total of 5835 age-associated DMHs were screened in 58 mouse blood samples(|rho|＞0.5,P＜0.01),accounting for 0.086%of DMHs.Finally,we validated the top 100 age-associated DMHs with high correlation in 95 independent samples,Resultsing in 44 loci.Conclusions The age-associated DMHs screened in this study may be useful in future studies of apparent age prediction using mouse blood and in aging studies.
关键词
血液/DNA甲基化微单倍型/Spearman秩相关系数/年龄/筛选Key words
blood/DNA methylation microhaplotype/Spearman's rank correlation coefficient/age/screening引用本文复制引用
基金项目
国家重点研发计划(2018YFA0801101)
出版年
2024
国家科技期刊平台
NSTL
万方数据