mCSEA

mCSEA identifies differentially methylated regions (DMRs) across the human genome using a Gene Set Enrichment Analysis approach applied to Illumina 450K and EPIC microarray methylation data to detect subtle and consistent methylation changes associated with complex phenotypes.

Key Features:

• Implementation as an R package: Provided as an R package for analysis of Illumina 450K and EPIC microarray methylation data.
• GSEA-based region detection: Uses Gene Set Enrichment Analysis tailored to methylation data to test enrichment of differential methylation across genomic regions.
• Detection of subtle methylation changes: Sensitive to moderate but consistent methylation differences relevant to complex phenotypes.
• Probe ranking by linear models: Ranks CpG probes using linear models prior to enrichment testing.
• Targets promoters and CpG islands: Tests predefined genomic areas such as promoters and CpG islands for differential methylation.
• Integration with gene expression data: Includes functions to integrate gene expression data to explore correlations between methylation patterns and gene expression levels.
• Validation on simulated and real datasets: Demonstrated superior performance on simulated datasets and identified differentially methylated promoters in sibling pairs discordant for intrauterine hyperglycemia, including genes associated with obesity and diabetes.

Scientific Applications:

• Epigenetics research: Identification of DMRs to study epigenetic contributions to complex disease etiology.
• Metabolic disorder studies: Detection of methylation changes linked to metabolic disorders, including obesity and diabetes.
• Cancer epigenomics: Application to identify DMRs relevant to cancer research.
• Neurological disease research: Detection of subtle methylation alterations implicated in neurological diseases.
• Integrated methylation–expression analyses: Correlation of methylation patterns with gene expression to investigate regulatory mechanisms.

Methodology:

mCSEA applies a Gene Set Enrichment Analysis approach to Illumina 450K and EPIC methylation arrays by ranking CpG probes using linear models and testing predefined genomic regions such as promoters and CpG islands for enrichment of differential methylation.