PEGS

PEGS evaluates gene-set enrichment relative to genomic peak data across variable distances to investigate transcriptional regulatory relationships between non-coding elements and genes.

Key Features:

• Python implementation: Provided as a Python-based computational utility for programmatic analysis of peak and gene-set data.
• Distance-aware enrichment: Computes enrichment of gene sets relative to peak sets across a configurable range of genomic distances, including distal ranges of tens to hundreds of kilobases from transcription start sites.
• Multiple gene and peak sets: Performs comparative enrichment analyses across multiple gene sets and multiple peak sets.
• TAD-aware analysis: Refines enrichment calculations within topologically associated domains (TADs) to account for 3D genome organization.
• Epigenomic integration: Integrates ChIP-seq and ATAC-seq peak data with gene sets derived from expression studies.
• GWAS/SNP integration: Tests enrichment of GWAS-associated single nucleotide polymorphisms (SNPs) within tissue-specific gene expression profiles (for example, sleep-associated SNPs).

Scientific Applications:

• Distal regulatory mapping: Identifying candidate regulatory links between distal non-coding elements and gene clusters located tens to hundreds of kilobases from transcription start sites.
• Epigenome–transcriptome integration: Associating ChIP-seq and ATAC-seq peaks with gene sets from expression studies to infer regulatory relationships.
• TAD-informed regulation: Assessing how 3D genome organization within TADs influences gene-set enrichments and regulatory interactions.
• Trait-associated SNP enrichment: Detecting enrichment of GWAS SNPs within tissue-specific gene sets to connect trait-associated variants to regulatory landscapes.
• Comparative tissue/condition analysis: Comparing enrichment patterns across multiple gene/peak sets and distances to reveal tissue- or condition-specific regulatory signatures.

Methodology:

Calculates enrichment of multiple gene sets relative to peak/peak-set locations across a range of genomic distances and optionally restricts analyses within topologically associated domains (TADs).