MethCoresProfiler

MethCoresProfiler profiles methylation patterns by identifying and tracing stable epialleles formed by phased methylated cytosines (mCpGs) within individual DNA molecules to characterize epigenetic variation in complex DNA populations.

Key Features:

• Phased CpG analysis: Targets CpG strings with discrete linear succession of phased methylated and non-methylated CpGs within the same DNA molecule.
• Identification of stable epialleles: Detects stable epialleles that are distinct from average single-nucleotide methylation measures and resilient to population heterogeneity.
• Methylation core extraction: Extracts "methylated cores" that are stable over time and that evolve via acquisition or loss of methyl sites.
• Tracking epiallele families: Identifies and traces combinations of methylated phased cytosines (mCpGs) shared across components of epiallele families.
• Noise and heterogeneity handling: Accounts for heterogeneity of 5'-3' molecule ends and reduces dilution by random unstable mCpGs.
• Implementation: Implemented as R-based software for computational analysis of methylation patterns.
• Validation: Validated on synthetic and in vivo cell populations derived from mouse brain areas and cells undergoing postnatal differentiation.

Scientific Applications:

• Epigenetic dynamics: Characterizes dynamics of DNA methylation across complex cell populations.
• Gene regulation studies: Resolves methylation patterns relevant to gene regulation by identifying phased methylation configurations.
• Development and differentiation: Traces epiallele changes during development and postnatal differentiation, including mouse brain cell populations.
• Disease and variability: Investigates epigenetic variability and potential disease-associated stable epialleles.
• Complex tissue analysis: Applies to studies of heterogeneous tissues or cell types where traditional single-nucleotide methylation analyses are insufficient.

Methodology:

R-based computational analysis that focuses on phased CpG strings to extract methylated cores, identify combinations of mCpGs, and trace epiallele families while accounting for 5'-3' end heterogeneity and unstable mCpGs.