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cpg island Definition and Methylation Mapping of the T2T-YAO Genome

GENOMICS PROTEOMICS & BIOINFORMATICS 2024年第2期22卷 qzae009页

作者： Xiao, Ming Wei, Rui Yu, Jun Gao, Chujie Yang, Fengyi Zhang, Le Sichuan Univ Coll Comp Sci Chengdu 610065 Peoples R China Univ Chinese Acad Sci Hangzhou Inst Adv Study Sch Life Sci Key Lab Syst Hlth Sci Zhejiang Prov Hangzhou 310024 Peoples R China Chinese Acad Sci Beijing Inst Genom CAS Key Lab Genome Sci & Informat Beijing 100101 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China

Precisely defining and mapping all cytosine (C) positions and their clusters, known as cpg islands (CGIs), as well as their methylation status, are pivotal for genome-wide epigenetic studies, especially when population-centric reference genomes are ready for timely application. Here, we first align the two high-quality reference genomes, T2T-YAO and T2T-CHM13, from different ethnic backgrounds in a base-by-base fashion and compute their genome-wide density-defined and position-defined CGIs. Second, by mapping some representative genome-wide methylation data from selected organs onto the two genomes, we find that there are about 4.7%-5.8% sequence divergency of variable categories depending on quality cutoffs. Genes among the divergent sequences are mostly associated with neurological functions. Moreover, CGIs associated with the divergent sequences are significantly different with respect to cpg density and observed cpg/expected cpg (O/E) ratio between the two genomes. Finally, we find that the T2T-YAO genome not only has a greater cpg coverage than that of the T2T-CHM13 genome when whole-genome bisulfite sequencing (WGBS) data from the European and American populations are mapped to each reference, but also shows more hyper-methylated cpg sites as compared to the T2T-CHM13 genome. Our study suggests that future genome-wide epigenetic studies of the Chinese populations rely on both acquisition of high-quality methylation data and subsequent precision CGI mapping based on the Chinese T2T reference.

关键词： T2T-YAO position-defined cpg island Density-defined cpg island DNA methylation Genome analysis DNA METHYLATION SURVIVAL DATABASE GENES

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