Prediction of genome-wide DNA methylation in repetitive elements

Abstract

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.

Genome-wide characterization of cytosine-specific 5-hydroxymethylation in normal breast tissue

“…Finally, while not providing the level of coverage achieved by next-generation sequencing-based (NGS) technologies, the arraybased approach used here provides a versatile balance between sample throughput, coverage, and cost, enabling effective population-scale profiling. Importantly, the 450 K array provides diverse coverage over unique genomic features, including CpG islands and their associated regions (shores, shelves, and open seas), promoters, enhancers, gene bodies, untranslated regions, MHC regions, and repetitive sequences [85,86]. For future research, both array-and NGS-based approaches will be valuable for improving our understanding of the tissue-specific distribution and function of 5hmC in human tissues.…”

Vitamin B12is neuroprotective in experimental pneumococcal meningitis through modulation of hippocampal DNA methylation

“…DNA methylation prevents genomic instability when occurring on interspersed repetitive sequences (IRSs) [61]. Actually, global DNA hypomethylation mostly reflects a decrease in DNA methylation of IRSs, which can cause genome instability [62,63]. Methyl-deficiency due to a variety of environmental influences causes a global decrease in 5mC content (DNA hypomethylation), which has been proposed as a molecular marker in multiple pathological processes [20].…”

Cell-specific Characterization of the Placental Methylome

“…The relationships we found for repetitive elements and global DNAm between cell types and CV were also largely consistent in our rst trimester samples (Additional File 5: Table S4, Additional File 1: Figure S11B). To determine genome-wide repetitive element DNAm, we used the random forestbased 'REMP' algorithm (39) to predict 438,664 Alu CpGs and 39,136 LINE1 CpGs that are not covered by the EPIC array. Relationships between cell types and CV for predicted and non-predicted repetitive elements were mostly the same, except TB DNAm in predicted Alu and LINE1 CpGs was not signi cantly different compared to CV (Additional File 5: Table S4, Additional File 1: Figure S11C).…”