DNA 5-methylcytosine detection and methylation phasing using PacBio circular consensus sequencing

Peng Ni, Fan Nie, Zeyu Zhong, Jinrui Xu, Neng Huang, Jun Zhang, Haochen Zhao, You Zou, Yuanfeng Huang, Jinchen Li, Chuan-Le Xiao (), Feng Luo () and Jianxin Wang ()
Additional contact information
Peng Ni: Central South University
Fan Nie: Central South University
Zeyu Zhong: Central South University
Jinrui Xu: Central South University
Neng Huang: Central South University
Jun Zhang: Central South University
Haochen Zhao: Central South University
You Zou: Central South University
Yuanfeng Huang: Xiangya Hospital, Central South University
Jinchen Li: Xiangya Hospital, Central South University
Chuan-Le Xiao: Sun Yat-sen University
Feng Luo: Clemson University
Jianxin Wang: Central South University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Long single-molecular sequencing technologies, such as PacBio circular consensus sequencing (CCS) and nanopore sequencing, are advantageous in detecting DNA 5-methylcytosine in CpGs (5mCpGs), especially in repetitive genomic regions. However, existing methods for detecting 5mCpGs using PacBio CCS are less accurate and robust. Here, we present ccsmeth, a deep-learning method to detect DNA 5mCpGs using CCS reads. We sequence polymerase-chain-reaction treated and M.SssI-methyltransferase treated DNA of one human sample using PacBio CCS for training ccsmeth. Using long (≥10 Kb) CCS reads, ccsmeth achieves 0.90 accuracy and 0.97 Area Under the Curve on 5mCpG detection at single-molecule resolution. At the genome-wide site level, ccsmeth achieves >0.90 correlations with bisulfite sequencing and nanopore sequencing using only 10× reads. Furthermore, we develop a Nextflow pipeline, ccsmethphase, to detect haplotype-aware methylation using CCS reads, and then sequence a Chinese family trio to validate it. ccsmeth and ccsmethphase can be robust and accurate tools for detecting DNA 5-methylcytosines.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-39784-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39784-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-39784-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().