Prediction of genome-wide DNA methylation in repetitive elements.
Journal Article (Journal Article)
DNA methylation in repetitive elements (RE) suppresses their mobility and maintains genomic stability, and decreases in it are frequently observed in tumor and/or surrogate tissues. Averaging methylation across RE in genome is widely used to quantify global methylation. However, methylation may vary in specific RE and play diverse roles in disease development, thus averaging methylation across RE may lose significant biological information. The ambiguous mapping of short reads by and high cost of current bisulfite sequencing platforms make them impractical for quantifying locus-specific RE methylation. Although microarray-based approaches (particularly Illumina's Infinium methylation arrays) provide cost-effective and robust genome-wide methylation quantification, the number of interrogated CpGs in RE remains limited. We report a random forest-based algorithm (and corresponding R package, REMP) that can accurately predict genome-wide locus-specific RE methylation based on Infinium array profiling data. We validated its prediction performance using alternative sequencing and microarray data. Testing its clinical utility with The Cancer Genome Atlas data demonstrated that our algorithm offers more comprehensively extended locus-specific RE methylation information that can be readily applied to large human studies in a cost-effective manner. Our work has the potential to improve our understanding of the role of global methylation in human diseases, especially cancer.
Full Text
Duke Authors
Cited Authors
- Zheng, Y; Joyce, BT; Liu, L; Zhang, Z; Kibbe, WA; Zhang, W; Hou, L
Published Date
- September 6, 2017
Published In
Volume / Issue
- 45 / 15
Start / End Page
- 8697 - 8711
PubMed ID
- 28911103
Pubmed Central ID
- PMC5587781
Electronic International Standard Serial Number (EISSN)
- 1362-4962
Digital Object Identifier (DOI)
- 10.1093/nar/gkx587
Language
- eng
Conference Location
- England