CoMeBack: DNA methylation array data analysis for co-methylated regions

• DOI: 10.1093/bioinformatics/btaa049
• Publication Date: 2020-01-21T04:23:18Z
• Authors: Evan Gatev; Nicole Gladish; Sara Mostafavi; Michael S Kobor
• Keywords: Methylated DNA immunoprecipitation

High-dimensional DNA methylation (DNAm) array coverage, while sparse in the context of entire methylome, still constitutes a very large number CpG probes. The ensuing multiple-test corrections affect statistical power to detect associations, likely contributing prevalent limited reproducibility. Array probes measuring proximal sites often have correlated levels DNAm that may not only be biologically meaningful but also imply dependence and redundancy. New methods account for such correlations between adjacent enable improved specificity, discovery interpretation associations data.We developed method named Co-Methylation with genomic Background (CoMeBack) estimates co-methylation, defined as across individuals. CoMeBack outputs co-methylated regions (CMRs), spanning sets constructed based on all sites, including those measured array, without any phenotypic variable inputs. This approach can reduce correction burden, enhancing specificity associations. We validated CMRs whole blood, using publicly available Illumina Infinium 450 K data from over 5000 These were enriched enhancer chromatin states, binding site motifs several transcription factors involved blood physiology. illustrated how CMR-based epigenome-wide association studies improve false positives chronological age.https://bitbucket.org/flopflip/comeback.Supplementary are at Bioinformatics online.