Integrative Methylation–Expression Correlation Analysis

Overview

This skill integrates differential methylation and differential expression datasets to reveal coordinated epigenetic regulation patterns.

• Refer to Inputs & Outputs to verify necessary files.
• Always prompt user for genome assembly used.
• Prepare the DMR regions into 6-column standard format BED file received by HOMER.
• Annotate the differential methylation regions to the gene promoter.
• Preprocess differential methylation and expression tables into a standard format.
• Integrate methylation and expression data by promoter proximity.
• Calculate correlation between methylation change and expression fold change.
• Classify patterns such as hypermethylation–downregulation or hypomethylation–upregulation.

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Inputs & Outputs

Inputs

dmr_results.txt # DMR results output by the metilene
dge_result.csv # DEG results output by DESeq2

Outputs

corr_DMR_DEG/
  stats/
    integrated_results.tsv
    pattern_counts.tsv
    summary_stats.tsv
    correlation_plot.pdf
  temp/
    homer_dmr.bed
    ... # Other temp files

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Decision Tree

Step 1: Prepare the DMR regions into 6-column standard format BED file received by HOMER

awk -F'\t' 'BEGIN {OFS="\t"} {print $1, $2, $3, "peak_"NR, "*", "+"}' dmr_results.txt > homer_dmr.bed

Step 2: Annotate the differential methylation regions to the gene promoter.

Call:

• mcp__homer-tools__homer_simple_annotate_peaks

with:

• peaks_path

  : 6-column standard format BED file from Step 1.

• genome

  : Provide by user.

• output_path

  : Output path of the annotated file

Step 3: Preprocess differential methylation and expression tables into a standard format

Call:

• mcp__methyl-tools__preprocess_differential_table

(1) with:

• input_path

  : dmr_results.txt

• output_path

• data_type

  : methyl

• source

  : metilene

(2) with:

• input_path

  : dge_result.csv

• output_path

• data_type

  : expr

• source

  : deseq2

Step 4: Integrate methylation and expression data by promoter proximity

Call:

• mcp__methyl-tools__integrate_methylation_expression

with:

methyl_path

: Path to standardized methylation TSV with columns: chr,start,end,pvalue,meth_diff (from Step 3)

methyl_annot_path

: Path to methylation annotation TSV from HOMER (from Step 2).

expr_path

: Path to standardized expression TSV with columns: gene,pvalue,log2FoldChange (from Step 3).

output_prefix

: Prefix for all output files (e.g. 'corr_DMR_DEG/stats/integrative').

methyl_diff

: Absolute methylation difference threshold (fraction points).

expr_fc

: Fold-change threshold for expression (absolute, e.g. 1.5 for 1.5x).