methylation-aggregationlisted

# Aggregate DNA Methylation Data Across Studies ## When to Use - User wants to build a tissue-level DNA methylation landscape from multiple WGBS experiments - User asks "where is DNA methylated in brain?" or "find hypomethylated regions across donors" - User needs to identify HMRs (hypomethylated regions), UMRs, or PMDs from aggregated WGBS data - User wants per-CpG weighted methylation averages from multiple experiments - Example queries: "aggregate WGBS data for liver", "build methylation map across donors", "find unmethylated CpG islands in pancreas" Build a comprehensive methylation landscape for a tissue/cell type by merging WGBS bedMethyl files from multiple ENCODE experiments. ## Scientific Rationale **The question**: "What is the DNA methylation state across the genome in my tissue?" DNA methylation is **fundamentally different** from histone marks and accessibility: | Property | Histone/Accessibility | DNA Methylation | |----------|----------------------|-----------------| | Signal type | Binary (bound/open or not) | Continuous (0-100% methylated) | | Default state | Unmarked | ~70-80% methylated (CpG context) | | Biology of interest | Where marks ARE present | Where methylation is ABSENT or REDUCED | | Aggregation approach | Union of peak calls | Average/median of methylation levels per CpG | **The key insight**: Unlike histone ChIP-seq where we want the union of all peaks, for methylation we want the **average methylation level per CpG site** across individ