FIREcaller

FIREcaller identifies frequently interacting regions (FIREs) from Hi-C contact matrices to detect tissue-specific chromatin interaction hotspots relevant to gene regulation.

Key Features:

• Detection of FIREs: Identifies frequently interacting regions (FIREs) that capture tissue-specific chromatin interactions distinct from A/B compartments, topologically associating domains (TADs), and chromatin loops.
• R implementation: Implemented as an R package for computational analysis of Hi-C data.
• Data input: Accepts raw Hi-C contact matrices as input.
• Normalization: Performs within-sample and cross-sample normalization to adjust for biases in raw contact matrices.
• Output options: Produces continuous FIRE scores, dichotomous FIRE calls, and super-FIREs for downstream analysis.

Scientific Applications:

• Tissue-specific gene regulation: Identifies FIREs associated with cell-type-specific regulatory regions to inform gene regulation analyses.
• Enhancer-promoter interactions: Detects FIREs and super-FIREs enriched for enhancer-promoter (E-P) interactions relevant to transcriptional control.
• Epigenomic signature overlap: Highlights regions that overlap epigenomic signatures indicative of cis-regulatory roles.
• GWAS interpretation: Aids interpretation of genome-wide association study (GWAS) variants by linking tissue-specific FIREs to potential regulatory mechanisms.

Methodology:

Processes raw Hi-C contact matrices and applies within-sample and cross-sample normalization to adjust for technical biases, then computes continuous FIRE scores and classifies dichotomous FIREs and super-FIREs.