Abstract

DNA methylation is an epigenetic modification that has the ability to alter gene expression without any change in the DNA sequence. DNA methylation occurs when a methyl chemical group attaches to cytosine bases on the DNA sequence. In mammals, DNA methylation primarily occurs at CG sites, when a cytosine is followed by a guanine in the DNA sequence. In plants, DNA methylation can also occur in other cytosine sequences, such as when a cytosine is not followed directly by a guanine. Many of the statistical methods that have been developed to estimate methylation levels and test differential methylation in whole-genome bisulfite sequencing studies incorporate the observed correlation between methylation levels of neighboring cytosine sites. However, most of these methods have been applied to human studies, where only CG sites are investigated. In this study, we focus on plant studies and show that the correlation between methylation levels at neighboring sites depends on the DNA sequence immediately following the cytosine. We investigate the importance of accounting for these differences in the correlation structure by comparing the performance of three existing methods (MethylSig, MAGI, and M3D) in plants.

Keywords

Methylation, Next-Generation Sequencing, Cytosine Context

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Comments to Editor

We would like to thank the reviewer for providing insightful feedback about our manuscript and the editor for the opportunity to revise our manuscript based on the review. Please find our updated manuscript and response to the reviewer attached.

Share

COinS
 
Jan 1st, 1:05 AM

DIFFERENTIAL METHYLATION METHODS IN MULTI-CONTEXT ORGANISMS

DNA methylation is an epigenetic modification that has the ability to alter gene expression without any change in the DNA sequence. DNA methylation occurs when a methyl chemical group attaches to cytosine bases on the DNA sequence. In mammals, DNA methylation primarily occurs at CG sites, when a cytosine is followed by a guanine in the DNA sequence. In plants, DNA methylation can also occur in other cytosine sequences, such as when a cytosine is not followed directly by a guanine. Many of the statistical methods that have been developed to estimate methylation levels and test differential methylation in whole-genome bisulfite sequencing studies incorporate the observed correlation between methylation levels of neighboring cytosine sites. However, most of these methods have been applied to human studies, where only CG sites are investigated. In this study, we focus on plant studies and show that the correlation between methylation levels at neighboring sites depends on the DNA sequence immediately following the cytosine. We investigate the importance of accounting for these differences in the correlation structure by comparing the performance of three existing methods (MethylSig, MAGI, and M3D) in plants.