Comprehensive Evaluation of Differential Methylation Analysis Methods for Bisulfite Sequencing Data
Abstract
:1. Background
2. Results and Discussion
2.1. Assessment of Performance in Detecting Differentially Methylated Cytosines
2.2. Assessment of Performance in Detecting Differentially Methylated Regions
2.3. Differential Analysis of Mouse Methylome
2.4. Differential Analysis of the Human Methylome
3. Conclusions
4. Materials and Methods
4.1. Simulation
4.2. RNA-Seq
4.3. DNase-Seq
4.4. BS-Seq
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Tool | Version | Model Assumption | Differential Methylation Test | Segmentation | Language | Smoothing |
---|---|---|---|---|---|---|
Fisher’s | 1.8.2 | - | Fisher’s exact test | tilling window | R | No |
BSmooth | 1.8.2 | binomial distribution | modified t-test | merging consecutive CpGs | R | Yes |
methylKit | 0.99.2 | logistic regression | logistic regression test | tilling window or predefined regions | R | No |
methylSig | 0.4.4 | beta-binomial model | likelihood ratio test | tilling window | R | No |
DSS | 2.12.0 | Bayesian hierarchical model | Wald test | merging CpGs based on p-value | R | No |
metilene | 0.2–6 | Nonparametric method | 2D Kolmogorov–Smirnov | circular binary segmentation | C | No |
RADMeth | - | beta-binomial regression | log-likelihood ratio test | correlation between p-value pairs within a bin | C++ | No |
Biseq | 1.12.0 | Beta regression model | Wald test | merging consecutive CpGs | R | Yes |
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Piao, Y.; Xu, W.; Park, K.H.; Ryu, K.H.; Xiang, R. Comprehensive Evaluation of Differential Methylation Analysis Methods for Bisulfite Sequencing Data. Int. J. Environ. Res. Public Health 2021, 18, 7975. https://doi.org/10.3390/ijerph18157975
Piao Y, Xu W, Park KH, Ryu KH, Xiang R. Comprehensive Evaluation of Differential Methylation Analysis Methods for Bisulfite Sequencing Data. International Journal of Environmental Research and Public Health. 2021; 18(15):7975. https://doi.org/10.3390/ijerph18157975
Chicago/Turabian StylePiao, Yongjun, Wanxue Xu, Kwang Ho Park, Keun Ho Ryu, and Rong Xiang. 2021. "Comprehensive Evaluation of Differential Methylation Analysis Methods for Bisulfite Sequencing Data" International Journal of Environmental Research and Public Health 18, no. 15: 7975. https://doi.org/10.3390/ijerph18157975
APA StylePiao, Y., Xu, W., Park, K. H., Ryu, K. H., & Xiang, R. (2021). Comprehensive Evaluation of Differential Methylation Analysis Methods for Bisulfite Sequencing Data. International Journal of Environmental Research and Public Health, 18(15), 7975. https://doi.org/10.3390/ijerph18157975