Introduction

Enhancers are cis-regulatory elements that activate transcription of target genes over large genomic distances through chromatin looping. The Activity-by-Contact (ABC) model predicts enhancer-gene regulatory interactions by combining enhancer activity (H3K27ac and ATAC-seq signals) with chromatin contact frequency (Hi-C).

Methods

Enhancer Activity

Enhancer activity = H3K27ac signal × ATAC-seq accessibility signal.

Contact Frequency

C(d) = d^(-0.87) × exp(-d/3×10^6), where d is genomic distance in bp.

ABC Score

ABC(e,g) = A_e × C(e,g) / Σ_{e'} A_{e'} × C(e',g), summed over all enhancers within 5Mb.

Results

Mean enhancer activity: 25.45 (Cell A) vs 6.72 (Cell B). Max ABC score: 0.882. Mean E-G distance: 100.4 kb. Cell-type-specific enhancers: 200 per type.

Code Availability

https://github.com/BioTender-max/EnhancerPromoterEngine

Key Results

• 1000 enhancers, 500 genes, 2 cell types
• Mean activity: A=25.45, B=6.72
• Max ABC score: 0.882
• Mean E-G distance: 100.4 kb