CpG Island Definition and Methylation Mapping of the T2T-YAO Genome  

作　　者：Ming Xiao Rui Wei Jun Yu Chujie Gao Fengyi Yang Le Zhang 

机构地区：[1]College of Computer Science,Sichuan University,Chengdu 610065,China [2]Key Laboratory of Systems Health Science of Zhejiang Province,School of Life Science,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,China [3]CAS Key Laboratory of Genome Sciences and Information,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China [4]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Genomics, Proteomics & Bioinformatics》2024年第2期69-79,共11页基因组蛋白质组与生物信息学报（英文版）

基　　金：supported by grants from the National Science and Technology Major Project(Grant Nos.2021YFF1201200 and 2018ZX10201002);the National Natural Science Foundation of China(Grant No.62372316);the China Postdoctoral Science Foundation(Grant No.2020M673221);the Fundamental Research Funds for the Central Universities(Grant No.2020SCU12056);the Sichuan Science and Technology Program(Grant No.2022YFS0048);the Chongqing Technology Innovation and Application Development Project(Grant No.CSTB2022TIAD-KPX0067),China.

摘　　要：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 

分 类 号：Q78[生物学—分子生物学]