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在细胞类型分辨率上对表观遗传衰老进行分析,通过长读序列测序

Alec Eames¹, Mahdi Moqri¹, Jesse R Poganik¹

¹Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

|July 2, 2025

概括

这项研究介绍了LongReadAge,一种使用长读序列测序来测量细胞类型特定的DNA甲基化衰老的新方法. 它从血液和无细胞DNA中揭示了不同细胞类型的不同衰老模式.

科学领域:

表观遗传学和基因组学
计算生物学计算生物学
衰老研究研究衰老研究

背景情况:

基因甲基化是衰老的关键生物标志物,但大量组织分析掩盖了细胞特异性的衰老差异.
现有的方法缺乏足够的分辨率来追踪单个细胞类型内的衰老轨迹.
长读测序为甲基化概况的细胞类型解卷提供了潜在的可能性.

研究的目的:

利用长读序列测序开发细胞类型特异性表观遗传年龄预测的框架.
介绍一个概率模型,LongReadAge,用于分析细胞类型级甲基化数据.
在没有细胞分类的情况下研究髓状细胞和淋巴细胞的衰老动态.

主要方法:

利用长读测序来对延长片段的DNA甲基化概况进行分析.
开发了一个计算框架,根据甲基化模式将碎片映射到细胞类型.
将LongReadAge模型应用于来自大量白细胞和无细胞DNA的细胞类型特定甲基化概况.

主要成果:

从散装和无细胞DNA成功生成了细胞类型特定的甲基化配置文件.
LongReadAge在细胞类型水平上准确预测了表观遗传年龄.
证明了髓状细胞和淋巴细胞的强大年龄预测,即使具有有限的共同特征.

结论:

开发的框架使细胞类型特定的表观遗传年龄分析能够在没有细胞分类的情况下进行.
LongReadAge提供了一种新的计算方法,以研究细胞分辨率的衰老动态.
这种方法为了解生物衰老过程中的异质性开辟了新的途径.

关键词:

老化的老化衰老的老化表观遗传学是指表观遗传学.长阅读序列编排长阅读序列编排

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