长读WGS的临床可行性用于DNA甲基化信号分析
Mathis Hildonen1, Luca Mariani2, Jonas Dalsberg1
1Department of Clinical Genetics, Copenhagen University Hospital, Copenhagen, Denmark.
Clinical genetics
|November 12, 2025
概括
长读测序 (LRS) 准确地捕获DNA甲基化 (DNAm) 概况,与用于诊断罕见遗传疾病的基于数组的方法保持一致. LRS为临床诊断提供了一个有前途的替代方案,使得同时进行甲基化和序列分析.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 生物标志物发现发现
背景情况:
- DNA甲基化 (DNAm) 标志是罕见遗传疾病的关键生物标志物.
- 基于数组的技术一直是DNAm签名分析的标准.
- 临床诊断越来越多地采用长读序列 (LRS) 而不是短读序列 (SRS).
研究的目的:
- 通过LRS平台 (PacBio,ONT) 生成的DNA甲基化配置文件与传统的DNA甲基化阵列进行比较.
- 评估LRS在罕见遗传疾病中的基于DNAm的诊断的可行性.
- 为了评估LRS和基于数组的DNAm签名之间的一致性.
主要方法:
- 使用DNAm数组对两个具有KMT2D变异的个体的DNA甲基化概况的分析.
- 使用PacBio和牛津纳米孔技术 (ONT) LRS平台生成DNAm配置文件.
- 使用了ONT多重测序与自适应采样.
- 采用在数组数据和EpigenCentral平台上训练的支持向量机 (SVM) 分类器进行预测.
主要成果:
- 由LRS生成的DNA甲基化概况显示与基于数组的签名有很强的对齐.
- 一个在阵列数据上训练的分类器正确预测了所有LRS样本的结果.
- LRS平台展示了基于DNAm的准确诊断的潜力.
结论:
- 长读测序平台可用于生成类似于基于数组的方法的DNA甲基化配置文件.
- 在基于DNAm的诊断中,LRS对临床和研究应用具有显著的前景.
- LRS提供了同时进行DNA甲基化和序列分析的优势.
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