1 Introduction

ATAC-seq, an assay for Transposase-Accessible Chromatin using sequencing, is a widely used technique for chromatin accessibility analysis. Detecting differential activation of transcription factors between two different experiment conditions provides the possibility of decoding the key factors in a phenotype. Lots of tools have been developed to detect the differential activity of TFs (DATFs) for different groups of samples. Those tools can be divided into two groups. One group detects DATFs from differential accessibility analysis, such as MEME1, HOMER2, enrichr3, and ChEA4. Another group finds the DATFs by enrichment tests, such as BiFET5, diffTF6, and TFEA7. For single-cell ATAC-seq analysis, Signac and chromVar are widely used tools.

2 Motivation

All of these tools detect the DATF by only considering the open status of chromatin. None of them take the TF footprint into count. The open status provides the possibility of TF can bind to that position. The TF footprint by ATAC-seq shows the status of TF bindings.

To help researchers quickly assess the differential activity of hundreds of TFs by detecting the difference in TF footprint via enrichment score8, we have developed the ATACseqTFEA package. The ATACseqTFEA package is a robust and reliable computational tool to identify the key regulators responding to a phenotype.