Cell-Free DNA Methylation Profiling Analysis—Technologies and Bioinformatics
Abstract
:1. Introduction
2. Technologies for DNA Methylation Detection
2.1. Restriction Enzyme-Based Methods
2.2. Bisulfite Conversion-Based Methods
2.2.1. Whole-Genome Bisulfite Sequencing (WGBS)
2.2.2. Reduced-Representation Bisulfite Sequencing (RRBS)
2.2.3. Methylated CpG Tandems Amplification and Sequencing (MCTA-seq)
2.2.4. Targeted Bisulfite Sequencing
2.2.5. Methylation Array
2.2.6. Methylation-specific PCR (MSP)
2.3. Enrichment-based methods
2.3.1. Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq)
2.3.2. Methyl-CpG Binding Domain Protein Capture Sequencing (MBD-seq)
2.4. 5-hydroxymethylation profiling
2.4.1. 5hmC-Seal (aka hMe-Seal)
2.4.2. hmC-CATCH
2.4.3. Hydroxymethylated DNA Immunoprecipitation Sequencing (hMeDIP-seq)
2.4.4. Oxidative Bisulfite Conversion
3. Bioinformatics Analysis of Sequencing-Based DNA Methylation Data
3.1. Alignment and Quality Controls
3.2. DNA Methylation Calling
3.3. Determination of Differential Methylation
3.4. Identification of Tumor-Specific Methylation Profile
4. Current Challenges and Future Directions
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Class | Technology | Strength | Weakness | Cost |
---|---|---|---|---|
Restriction enzyme-based | -High CGI coverage | -Low resolution -Limited to regions in proximity to restriction enzyme sites | ||
qPCR or ddPCR | -Allows ultra-low DNA input -Easy primer design | -Loci-specific studies only | Low | |
Bisulfite-based | -Single-based resolution | -Substantial DNA degradation during bisulfite treatment -Cannot discriminate between 5mC and 5hmC | ||
WGBS | -The most comprehensive profiling of the whole methylome | -Relatively low sequencing depth | High | |
RRBS | -High CGIs coverage | -Limited to regions in proximity to restriction enzyme sites | Moderate | |
MTCA-seq | -High CGIs coverage | -Limited to CGIs and might decrease other methylation backgrounds | Moderate | |
Targeted | -Detect target CpG sites at high coverage | -Complicated primer or probe design | Low | |
Microarray | -Pre-designed panel covering hotspot methylation | -Low genome-wide coverage of CpGs | Low | |
qMSP or ddMSP | -Allows ultra-low DNA input | -Loci-specific studies only -Complicated primer or probe design | Low | |
Enrichment-based | -No mutation introduced | -Low resolution -Biased toward hypermethylated regions | ||
MeDIP-seq | -Antibody is specific to 5mC | -Less sensitive in regions with high CpG density than MBD-seq | Moderate | |
5hmC profiling | -Specific to 5hmC | -High sequencing depth is required as 5hmC has a low abundance | ||
5hmC-Seal | -Ensures accurate capture of DNA containing 5hmC | -Low resolution | Moderate | |
hmC-CATCH | -Single-based resolution | -Oxidative environment would cause DNA damage | Moderate |
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Huang, J.; Wang, L. Cell-Free DNA Methylation Profiling Analysis—Technologies and Bioinformatics. Cancers 2019, 11, 1741. https://doi.org/10.3390/cancers11111741
Huang J, Wang L. Cell-Free DNA Methylation Profiling Analysis—Technologies and Bioinformatics. Cancers. 2019; 11(11):1741. https://doi.org/10.3390/cancers11111741
Chicago/Turabian StyleHuang, Jinyong, and Liang Wang. 2019. "Cell-Free DNA Methylation Profiling Analysis—Technologies and Bioinformatics" Cancers 11, no. 11: 1741. https://doi.org/10.3390/cancers11111741
APA StyleHuang, J., & Wang, L. (2019). Cell-Free DNA Methylation Profiling Analysis—Technologies and Bioinformatics. Cancers, 11(11), 1741. https://doi.org/10.3390/cancers11111741