Identification of transcription factor binding sites using ATAC-seq

Genome Biol. 2019 Feb 26;20(1):45. doi: 10.1186/s13059-019-1642-2.


Transposase-Accessible Chromatin followed by sequencing (ATAC-seq) is a simple protocol for detection of open chromatin. Computational footprinting, the search for regions with depletion of cleavage events due to transcription factor binding, is poorly understood for ATAC-seq. We propose the first footprinting method considering ATAC-seq protocol artifacts. HINT-ATAC uses a position dependency model to learn the cleavage preferences of the transposase. We observe strand-specific cleavage patterns around transcription factor binding sites, which are determined by local nucleosome architecture. By incorporating all these biases, HINT-ATAC is able to significantly outperform competing methods in the prediction of transcription factor binding sites with footprints.

Keywords: ATAC-seq; Cleavage bias; Computational footprinting; Open chromatin.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Footprinting / methods*
  • Dendritic Cells / metabolism
  • Genomics / methods*
  • Humans
  • K562 Cells
  • Mice
  • Models, Genetic*
  • Nucleosomes / chemistry
  • Sequence Analysis, DNA / methods*
  • Transcription Factors / metabolism*
  • Transposases / metabolism


  • Nucleosomes
  • Tn5 transposase
  • Transcription Factors
  • Transposases