Protocol for discovering genetic variants associated with ATAC-seq footprint-inferred transcription factor binding

Transcription factor (TF) binding is detectable in assay for transposase-accessible chromatin using sequencing (ATAC-seq) experiments, where bound TFs block transposase insertions, leaving a depletion of insertions known as a "footprint." Here, we present a computational protocol for detecting genetic variants associated with footprint-inferred TF binding. We describe steps to run the PRINT footprinting software to quantify TF binding likelihood at variants across multiple genotyped ATAC-seq samples and then run regressions to measure genetic associations. This protocol can implicate causal variants in disease-associated loci. For complete details on the use and execution of this protocol, please refer to Dudek et al.¹.