Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.671302
Keywords
whole-genome bisulfite sequencing; reduced-representation bisulfite sequencing; targeted bisulfite sequencing; liver cancer; DNA methylation
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Funding
- Guangdong Basic and Applied Basic Research Foundation [2019A1515110097]
- Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections [ZDSYS20200811142804014]
- Shenzhen Key Medical Discipline Construction Fund
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This study introduced the most prevalent methods for processing bisulfite sequencing data and evaluated the consistency of the data acquired from different measurements in liver cancer. Differential methylated genes measured by various bisulfite sequencing assays and 450 k beadchip were consistently hypo-methylated in liver cancer with high functional similarity.
Bisulfite sequencing is considered as the gold standard approach for measuring DNA methylation, which acts as a pivotal part in regulating a variety of biological processes without changes in DNA sequences. In this study, we introduced the most prevalent methods for processing bisulfite sequencing data and evaluated the consistency of the data acquired from different measurements in liver cancer. Firstly, we introduced three commonly used bisulfite sequencing assays, i.e., reduced-representation bisulfite sequencing (RRBS), whole-genome bisulfite sequencing (WGBS), and targeted bisulfite sequencing (targeted BS). Next, we discussed the principles and compared different methods for alignment, quality assessment, methylation level scoring, and differentially methylated region identification. After that, we screened differential methylated genes in liver cancer through the three bisulfite sequencing assays and evaluated the consistency of their results. Ultimately, we compared bisulfite sequencing to 450 k beadchip and assessed the statistical similarity and functional association of differentially methylated genes (DMGs) among the four assays. Our results demonstrated that the DMGs measured by WGBS, RRBS, targeted BS and 450 k beadchip are consistently hypo-methylated in liver cancer with high functional similarity.
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