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A new approach to decode DNA methylome and genomic variants simultaneously from double strand bisulfite sequencing

Genetic and epigenetic contributions to various diseases and biological processes have been well-recognized. However, simultaneous identification of single-nucleotide variants (SNVs) and DNA methylation levels from traditional bisulfite sequencing data is still challenging. Here, we develop double s...

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Autores principales: Liang, Jialong, Zhang, Kun, Yang, Jie, Li, Xianfeng, Li, Qinglan, Wang, Yan, Cai, Wanshi, Teng, Huajing, Sun, Zhongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575003/
https://www.ncbi.nlm.nih.gov/pubmed/34058751
http://dx.doi.org/10.1093/bib/bbab201
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author Liang, Jialong
Zhang, Kun
Yang, Jie
Li, Xianfeng
Li, Qinglan
Wang, Yan
Cai, Wanshi
Teng, Huajing
Sun, Zhongsheng
author_facet Liang, Jialong
Zhang, Kun
Yang, Jie
Li, Xianfeng
Li, Qinglan
Wang, Yan
Cai, Wanshi
Teng, Huajing
Sun, Zhongsheng
author_sort Liang, Jialong
collection PubMed
description Genetic and epigenetic contributions to various diseases and biological processes have been well-recognized. However, simultaneous identification of single-nucleotide variants (SNVs) and DNA methylation levels from traditional bisulfite sequencing data is still challenging. Here, we develop double strand bisulfite sequencing (DSBS) for genome-wide accurate identification of SNVs and DNA methylation simultaneously at a single-base resolution by using one dataset. Locking Watson and Crick strand together by hairpin adapter followed by bisulfite treatment and massive parallel sequencing, DSBS simultaneously sequences the bisulfite-converted Watson and Crick strand in one paired-end read, eliminating the strand bias of bisulfite sequencing data. Mutual correction of read1 and read2 can estimate the amplification and sequencing errors, and enables our developed computational pipeline, DSBS Analyzer (https://github.com/tianguolangzi/DSBS), to accurately identify SNV and DNA methylation. Additionally, using DSBS, we provide a genome-wide hemimethylation landscape in the human cells, and reveal that the density of DNA hemimethylation sites in promoter region and CpG island is lower than that in other genomic regions. The cost-effective new approach, which decodes DNA methylome and genomic variants simultaneously, will facilitate more comprehensive studies on numerous diseases and biological processes driven by both genetic and epigenetic variations.
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spelling pubmed-85750032021-11-09 A new approach to decode DNA methylome and genomic variants simultaneously from double strand bisulfite sequencing Liang, Jialong Zhang, Kun Yang, Jie Li, Xianfeng Li, Qinglan Wang, Yan Cai, Wanshi Teng, Huajing Sun, Zhongsheng Brief Bioinform Problem Solving Protocol Genetic and epigenetic contributions to various diseases and biological processes have been well-recognized. However, simultaneous identification of single-nucleotide variants (SNVs) and DNA methylation levels from traditional bisulfite sequencing data is still challenging. Here, we develop double strand bisulfite sequencing (DSBS) for genome-wide accurate identification of SNVs and DNA methylation simultaneously at a single-base resolution by using one dataset. Locking Watson and Crick strand together by hairpin adapter followed by bisulfite treatment and massive parallel sequencing, DSBS simultaneously sequences the bisulfite-converted Watson and Crick strand in one paired-end read, eliminating the strand bias of bisulfite sequencing data. Mutual correction of read1 and read2 can estimate the amplification and sequencing errors, and enables our developed computational pipeline, DSBS Analyzer (https://github.com/tianguolangzi/DSBS), to accurately identify SNV and DNA methylation. Additionally, using DSBS, we provide a genome-wide hemimethylation landscape in the human cells, and reveal that the density of DNA hemimethylation sites in promoter region and CpG island is lower than that in other genomic regions. The cost-effective new approach, which decodes DNA methylome and genomic variants simultaneously, will facilitate more comprehensive studies on numerous diseases and biological processes driven by both genetic and epigenetic variations. Oxford University Press 2021-05-31 /pmc/articles/PMC8575003/ /pubmed/34058751 http://dx.doi.org/10.1093/bib/bbab201 Text en © The Author(s) 2021. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Problem Solving Protocol
Liang, Jialong
Zhang, Kun
Yang, Jie
Li, Xianfeng
Li, Qinglan
Wang, Yan
Cai, Wanshi
Teng, Huajing
Sun, Zhongsheng
A new approach to decode DNA methylome and genomic variants simultaneously from double strand bisulfite sequencing
title A new approach to decode DNA methylome and genomic variants simultaneously from double strand bisulfite sequencing
title_full A new approach to decode DNA methylome and genomic variants simultaneously from double strand bisulfite sequencing
title_fullStr A new approach to decode DNA methylome and genomic variants simultaneously from double strand bisulfite sequencing
title_full_unstemmed A new approach to decode DNA methylome and genomic variants simultaneously from double strand bisulfite sequencing
title_short A new approach to decode DNA methylome and genomic variants simultaneously from double strand bisulfite sequencing
title_sort new approach to decode dna methylome and genomic variants simultaneously from double strand bisulfite sequencing
topic Problem Solving Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575003/
https://www.ncbi.nlm.nih.gov/pubmed/34058751
http://dx.doi.org/10.1093/bib/bbab201
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