MAM-pipeline

MAM-pipeline identifies monoallelically methylated loci by integrating MethylCap-seq methylomic data with associated SNP profiles using Hardy-Weinberg equilibrium to detect loci relevant for imprinting and promoter-associated gene regulation.

Key Features:

• Hardy-Weinberg integration: Uses the Hardy-Weinberg theorem to correlate SNP profiles with enrichment-based methylomic signals for detection of monoallelic methylation.
• MethylCap-seq-based analysis: Processes MethylCap-seq enrichment data as the primary input for methylomic profiling.
• Monoallelic locus discovery: Identified 80 genomic regions exhibiting monoallelic DNA methylation from an analysis of 334 MethylCap-seq samples.
• Genic and imprinting annotations: Reports 49 loci within genic regions, of which 25 are previously associated with imprinting.
• Promoter enrichment analysis: Performs statistical analysis revealing significant enrichment of monoallelic methylation in promoter regions.
• Validation with orthogonal data: Validates methylation calls using 14 whole-genome bisulfite sequencing datasets and 16 mRNA-seq datasets.
• Applicability to other enrichment assays: Adaptable to other enrichment-based sequencing technologies, such as ChIP-seq, to identify monoallelic histone modifications.

Scientific Applications:

• Non-Mendelian inheritance studies: Enables investigation of disorders linked to dysregulation of monoallelic gene expression.
• Imprinting and gene regulation: Facilitates identification of imprinted loci and analysis of promoter methylation's role in gene regulation.
• Epigenetic modification profiling: Applicable to detect monoallelic histone modifications when applied to ChIP-seq datasets.

Methodology:

Integrates MethylCap-seq methylomic data with associated SNP profiles using the Hardy-Weinberg equilibrium; applies statistical analysis for promoter enrichment; analysis performed on 334 MethylCap-seq samples with validation using 14 whole-genome bisulfite sequencing and 16 mRNA-seq datasets.