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

Peng Ni, Jinrui Xu, Zeyu Zhong, Jun Zhang, Neng Huang, Fan Nie, Feng Luo, Jianxin Wang
doi: https://doi.org/10.1101/2022.02.26.482074
Peng Ni
1School of Computer Science and Engineering, Central South University, Changsha, 410083, China
2Hunan Provincial Key Lab on Bioinformatics, Central South University, Changsha, 410083, China
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Jinrui Xu
1School of Computer Science and Engineering, Central South University, Changsha, 410083, China
2Hunan Provincial Key Lab on Bioinformatics, Central South University, Changsha, 410083, China
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Zeyu Zhong
1School of Computer Science and Engineering, Central South University, Changsha, 410083, China
2Hunan Provincial Key Lab on Bioinformatics, Central South University, Changsha, 410083, China
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Jun Zhang
1School of Computer Science and Engineering, Central South University, Changsha, 410083, China
2Hunan Provincial Key Lab on Bioinformatics, Central South University, Changsha, 410083, China
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Neng Huang
1School of Computer Science and Engineering, Central South University, Changsha, 410083, China
2Hunan Provincial Key Lab on Bioinformatics, Central South University, Changsha, 410083, China
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Fan Nie
1School of Computer Science and Engineering, Central South University, Changsha, 410083, China
2Hunan Provincial Key Lab on Bioinformatics, Central South University, Changsha, 410083, China
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Feng Luo
3School of Computing, Clemson University, Clemson, SC, 29634-0974, USA
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  • For correspondence: luofeng@clemson.edu jxwang@mail.csu.edu.cn
Jianxin Wang
1School of Computer Science and Engineering, Central South University, Changsha, 410083, China
2Hunan Provincial Key Lab on Bioinformatics, Central South University, Changsha, 410083, China
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  • For correspondence: luofeng@clemson.edu jxwang@mail.csu.edu.cn
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Abstract

It has been reported recently that DNA 5-methylcytosine (5mC) in CpG contexts can be detected using PacBio circular consensus sequencing (CCS). However, the accuracy and robustness of computational methods using long CCS reads still need to be improved. In this study, we present a deep learning method, ccsmeth, to detect DNA 5mCpGs from PacBio CCS subreads. ccsmeth utilizes attention-based bidirectional Gated Recurrent Unit (GRU) networks to infer DNA methylation states. Testing ccsmeth using CCS subreads of amplified DNA and M.SssI-treated DNA, we found that ccsmeth achieved higher performances than existing methods. We also compared the results of ccsmeth on long CCS reads with bisulfite sequencing and Nanopore sequencing. The results demonstrated that ccsmeth can accurately detect 5mCpGs from CCS data sequenced using >10 kb insert library. Moreover, using PacBio CCS data, we proposed a pipeline which can detect haplotype-aware methylation in human.

Competing Interest Statement

The authors have declared no competing interest.

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Posted March 01, 2022.
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DNA 5-methylcytosine detection and methylation phasing using PacBio circular consensus sequencing
Peng Ni, Jinrui Xu, Zeyu Zhong, Jun Zhang, Neng Huang, Fan Nie, Feng Luo, Jianxin Wang
bioRxiv 2022.02.26.482074; doi: https://doi.org/10.1101/2022.02.26.482074
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DNA 5-methylcytosine detection and methylation phasing using PacBio circular consensus sequencing
Peng Ni, Jinrui Xu, Zeyu Zhong, Jun Zhang, Neng Huang, Fan Nie, Feng Luo, Jianxin Wang
bioRxiv 2022.02.26.482074; doi: https://doi.org/10.1101/2022.02.26.482074

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