ABC

ABC identifies allele-specific binding (ASB) of transcription factors at heterozygous single nucleotide variants (SNVs) using aligned ChIP-Seq reads to detect functional non-coding variants that modulate transcription factor–chromatin interactions.

Key Features:

• Allele-Specific Binding Detection: Identifies differences in transcription factor binding at heterozygous SNVs using aligned ChIP-Seq reads.
• Bias Control Mechanism: Incorporates methods to control for biases introduced by short-read ChIP-Seq data to reduce false-positive ASB calls.
• Statistical ASB Inference: Employs statistical methods to distinguish true ASB events from background noise.
• Scalability: Scales to process large numbers of heterozygous SNVs for high-throughput genomic studies.
• Validation with Known Variants: Validated against characterized functional SNVs such as rs4784227, which modulates FOXA1 binding and is associated with breast cancer.

Scientific Applications:

• Elucidating Gene Regulation: Detects allele-specific transcription factor binding events to reveal how non-coding SNVs influence regulatory element function and gene expression.
• Disease Association Studies: Identifies functional regulatory variants that can be linked to disease risk, exemplified by variants associated with cancer.
• Transcription Factor Binding Analysis: Characterizes allele-resolved transcription factor binding landscapes to study chromatin dynamics and epigenetic regulation.

Methodology:

Uses aligned ChIP-Seq reads to detect allele-specific differences in transcription factor binding at heterozygous SNVs; employs statistical methods to distinguish true ASB events from background noise and accounts for biases introduced by short-read sequencing; requires PERL (≥5.18.1), R (≥3.1.1), and the PERL Statistics::R module.