Identification of transcription factor binding sites using ATAC-seq

• Published in: Genome Biology Vol. 20; no. 1; pp. 45 - 21
• Main Authors: Li, Zhijian, Schulz, Marcel H, Look, Thomas, Begemann, Matthias, Zenke, Martin, Costa, Ivan G
• Format: Journal Article
• Language: English
• Published: England BioMed Central 26.02.2019; BMC
• Subjects: Accuracy; Animals; ATAC-seq; Bias; Binding sites; Chromatin; Cleavage bias; Computational footprinting; Computer applications; Dendritic Cells - metabolism; Deoxyribonucleic acid; DNA; DNA Footprinting - methods; Enzymes; Experiments; Footprinting; Gene expression; Genomes; Genomics - methods; Humans; K562 Cells; Method; Methods; Mice; Models, Genetic; Nucleosomes - chemistry; Open chromatin; Sequence Analysis, DNA - methods; Studies; Transcription factors; Transcription Factors - metabolism; Transposase; Transposases - metabolism; Computational footprinting; Open chromatin; ATAC-seq; Cleavage bias
• ISSN: 1474-760X; 1474-7596; 1474-760X
• 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.