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Regression-based toolkit for modeling sequence effects on transcription factor binding using accessible chromatin as probes

Project description

EUbar

EUbar predicts the effect of noncoding single nucleotide variants on transcription factor binding affinity using accessible chromatin regions as sequence probes and matched ChIP-seq signal as a measure of binding intensity. It also supports whole-region scanning for mutational effect landscapes and affinity-based motif discovery.

EUbar method summary


Installation

git clone https://github.com/SvenBaileyLab/EUbar
cd EUbar
pip install .

Confirm the install:

eubar --help

Workflow overview

Every EUbar analysis follows three steps:

  1. Build an array file — index all k-mers in your accessible regions
  2. Compute probe intensities — summarise ChIP-seq signal across those regions
  3. Run analysis — predict SNV effects, scan a region, or discover motifs

Commands

Command Description
array Build a k-mer index from a BED file and genome FASTA
intensities Compute GC-corrected probe intensities from a BigWig or BedGraph signal track
snv Predict the effect of one or more SNVs on TF binding
scan Scan a genomic region for predicted binding effects at every position
motifs Derive an affinity-based TF binding motif from probe intensities

Command-specific help is available with eubar <command> --help.


Quick start

# 1. Build array
eubar array   --bed regions.bed   --genome hg38.fa   --kmer-size 8   --output regions_8mer.txt

# 2. Compute intensities
eubar intensities   --bed regions.bed   --signal tf_chipseq.bw   --genome-fasta hg38.fa   --output probe_intensities.tsv

# 3. Predict SNV effect
eubar snv   --intensities probe_intensities.tsv   --array regions_8mer.txt   --genome hg38.fa   --snv-list "chr5:1295113:C>T"   --best-pval

Tutorials

Step-by-step tutorials using real ENCODE data (MCF7 DNase-seq + GABPA ChIP-seq):


Citation

If you use EUbar in your research, please cite:

[manuscript citation — to be added on publication]


License

GNU General Public License v3.0.

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