CoMeBack

CoMeBack estimates DNA co-methylation by identifying proximal CpG probes with correlated DNA methylation across individuals to define co-methylated regions (CMRs) that improve specificity in DNA methylation array analyses.

Key Features:

• Co-Methylated Regions (CMRs): Constructs CMRs from sets of array probes using genomic CpG information including both measured and unmeasured CpGs.
• Multiple-test correction reduction: Accounts for statistical dependencies between adjacent probes to reduce the multiple-testing burden and increase power to detect associations.
• Correlation-based specificity: Leverages correlations among proximal CpG sites to refine identification of biologically significant methylation regions.
• Empirical validation: Validated on Illumina Infinium 450K array data from over 5,000 individuals, with CMRs enriched for enhancer chromatin states and transcription factor binding motifs relevant to blood physiology.

Scientific Applications:

• Epigenome-wide association studies (EWAS): Facilitates EWAS by improving discovery of associations and reducing false positives, as demonstrated in studies of chronological age.
• Functional genomic interpretation: Identifies regions enriched for enhancers and transcription factor binding motifs to support interpretation of regulatory features in methylation studies.

Methodology:

Identifies proximal CpG probes exhibiting correlated DNA methylation across individuals and groups them into co-methylated regions (CMRs) using a genomic CpG background that includes measured and unmeasured CpGs; validated on Illumina Infinium 450K array data from over 5,000 individuals.