通过长读序列分析细胞类型分辨率下的表观遗传衰老。

IF 7.1 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Aging Cell Pub Date : 2025-07-02 DOI:10.1111/acel.70084
Alec Eames, Mahdi Moqri, Jesse R. Poganik, Vadim N. Gladyshev
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引用次数: 0

摘要

DNA甲基化可以产生强大的衰老生物标志物,但大多数研究将其描述为整体组织水平,这掩盖了可能遵循不同衰老轨迹的细胞类型特异性改变。长读测序技术能够对延伸的DNA片段进行甲基化分析,从而能够映射到它们的细胞类型。在这项研究中,我们引入了一个框架来评估细胞类型特异性老化使用长读测序数据,而不需要细胞分选。利用细胞类型特异性甲基化模式,我们将长读片段映射到单个细胞类型,并生成细胞类型特异性甲基化谱,这些甲基化谱被用作新开发的概率衰老模型LongReadAge的输入,该模型能够在细胞类型水平上预测表观遗传年龄。我们使用LongReadAge从大量白细胞数据以及循环无细胞DNA中跟踪骨髓细胞和淋巴细胞的衰老,尽管样本之间的共同特征有限,但在预测年龄方面表现出强大的性能。这种方法为在细胞类型分辨率上分析表观遗传衰老的动力学提供了一种新的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Profiling Epigenetic Aging at Cell-Type Resolution Through Long-Read Sequencing

Profiling Epigenetic Aging at Cell-Type Resolution Through Long-Read Sequencing

DNA methylation can give rise to robust biomarkers of aging, yet most studies profile it at the bulk tissue level, which masks cell type-specific alterations that may follow distinct aging trajectories. Long-read sequencing technology enables methylation profiling of extended DNA fragments, enabling mapping to their cell type of origin. In this study, we introduce a framework for evaluating cell type-specific aging using long-read sequencing data, without the need for cell sorting. Leveraging cell type-specific methylation patterns, we map long-read fragments to individual cell types and generate cell type-specific methylation profiles, which are used as input to a newly developed probabilistic aging model, LongReadAge, capable of predicting epigenetic age at the cell type level. We use LongReadAge to track aging of myeloid cells and lymphocytes from bulk leukocyte data as well as circulating cell-free DNA, demonstrating robust performance in predicting age despite limited shared features across samples. This approach provides a novel method for profiling the dynamics of epigenetic aging at cell type resolution.

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来源期刊
Aging Cell
Aging Cell 生物-老年医学
CiteScore
14.40
自引率
2.60%
发文量
212
审稿时长
8 weeks
期刊介绍: Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.
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