Comprehensive Evaluation of Differential Methylation Analysis Methods for Bisulfite Sequencing Data

Yongjun Piao, Wanxue Xu, Kwang Ho Park, Keun Ho Ryu and Rong Xiang
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Yongjun Piao: School of Medicine, Nankai University, Tianjin 300071, China
Wanxue Xu: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
Kwang Ho Park: Department of Computer Science, College of Electrical and Computer Engineering, Chungbuk National University, Cheongju 28644, Korea
Keun Ho Ryu: Faculty of Information Technology, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam
Rong Xiang: School of Medicine, Nankai University, Tianjin 300071, China

IJERPH, 2021, vol. 18, issue 15, 1-15

Abstract: Background: With advances in next-generation sequencing technologies, the bisulfite conversion of genomic DNA followed by sequencing has become the predominant technique for quantifying genome-wide DNA methylation at single-base resolution. A large number of computational approaches are available in literature for identifying differentially methylated regions in bisulfite sequencing data, and more are being developed continuously. Results: Here, we focused on a comprehensive evaluation of commonly used differential methylation analysis methods and describe the potential strengths and limitations of each method. We found that there are large differences among methods, and no single method consistently ranked first in all benchmarking. Moreover, smoothing seemed not to improve the performance greatly, and a small number of replicates created more difficulties in the computational analysis of BS-seq data than low sequencing depth. Conclusions: Data analysis and interpretation should be performed with great care, especially when the number of replicates or sequencing depth is limited.

Keywords: differentially methylated regions; DNA methylation; BS-seq (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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