基于长读长测序的DNA甲基化计算分析

Computational analysis of DNA methylation from long-read sequencing.

作者信息

Fu Yilei, Timp Winston, Sedlazeck Fritz J

机构信息

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.

出版信息

Nat Rev Genet. 2025 Mar 28. doi: 10.1038/s41576-025-00822-5.

DOI:10.1038/s41576-025-00822-5

PMID:40155770

Abstract

DNA methylation is a critical epigenetic mechanism in numerous biological processes, including gene regulation, development, ageing and the onset of various diseases such as cancer. Studies of methylation are increasingly using single-molecule long-read sequencing technologies to simultaneously measure epigenetic states such as DNA methylation with genomic variation. These long-read data sets have spurred the continuous development of advanced computational methods to gain insights into the roles of methylation in regulating chromatin structure and gene regulation. In this Review, we discuss the computational methods for calling methylation signals, contrasting methylation between samples, analysing cell-type diversity and gaining additional genomic insights, and then further discuss the challenges and future perspectives of tool development for DNA methylation research.

摘要

DNA甲基化是众多生物学过程中的一种关键表观遗传机制，包括基因调控、发育、衰老以及各种疾病（如癌症）的发生。甲基化研究越来越多地使用单分子长读长测序技术，以同时测量诸如DNA甲基化等表观遗传状态与基因组变异。这些长读长数据集推动了先进计算方法的不断发展，以便深入了解甲基化在调节染色质结构和基因调控中的作用。在本综述中，我们讨论了用于识别甲基化信号、对比样本间甲基化、分析细胞类型多样性以及获得更多基因组见解的计算方法，然后进一步讨论了DNA甲基化研究工具开发面临的挑战和未来前景。