DMRscaler

DMRscaler identifies differential DNA methylation regions (DMRs) across epigenetic scales, detecting changes from single basepair modifications to multi-megabase and chromosome-scale features to map epigenetic dysregulation.

Key Features:

• Scale-Aware Detection: Employs an iterative windowing procedure to capture DMRs across a continuum of sizes, from ~100 base pairs up to 152 megabases, including chromosome-scale features on the X chromosome.
• Iterative Windowing Procedure: Uses successive window sizes to aggregate CpG-level signals for detection of DMRs spanning disparate genomic scales.
• Benchmarking and Accuracy: Demonstrated high concordance in comparative analyses with simulated and natural datasets (including XX vs XY peripheral blood samples), yielding a Pearson correlation coefficient of 0.94 for DMRs sized 100 bp–1 Mb.
• Novel Region Identification: Detects DMRs in cohorts with mutations in chromatin modifier genes such as NSD1, EZH2, and KAT6A, identifying multi-gene clusters implicated in developmental processes.
• Co-regulated Region Detection: Identifies co-regulated genomic regions that may drive coordinated epigenetic changes.

Scientific Applications:

• Epigenetic dysregulation in human disease: Mapping DMRs across scales to study altered DNA methylation patterns associated with disease states.
• Rare genetic syndromes with disrupted chromatin function: Analyzing methylation changes in cohorts carrying mutations in NSD1, EZH2, and KAT6A.
• Discovery of co-regulated regions and candidate targets: Identifying multi-gene and chromosome-scale methylation changes that inform mechanisms and potential therapeutic targets.

Methodology:

Uses an iterative windowing procedure to scan multiple window sizes for DMR detection and was benchmarked on simulated and natural datasets (including XX vs XY peripheral blood samples), reporting a Pearson correlation of 0.94 for 100 bp–1 Mb DMRs.