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

Identification of transcription factor binding sites using ATAC-seq.

Li Z1,2, Schulz MH3,4,5,6, Look T2,7, Begemann M8, Zenke M2,7, Costa IG9,10.

Author information

1
Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen University Medical School, Aachen, 52074, Germany.
2
Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, 52074, Germany.
3
Cluster of Excellence for Multimodal Computing and Interaction, Saarland Informatics Campus, Saarland University, Saarbrücken, Germany.
4
Computational Biology & Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany.
5
Institute for Cardiovascular Regeneration, Goethe University, Frankfurt am Main, Germany.
6
German Centre for Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, Germany.
7
Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany.
8
Institute of Human Genetics, RWTH Aachen University Medical School, Aachen, Germany.
9
Institute for Computational Genomics, Joint Research Center for Computational Biomedicine, RWTH Aachen University Medical School, Aachen, 52074, Germany. ivan.costa@rwth-aachen.de.
10
Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany. ivan.costa@rwth-aachen.de.

Abstract

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

PMID:
30808370
PMCID:
PMC6391789
DOI:
10.1186/s13059-019-1642-2
[Indexed for MEDLINE]
Free PMC Article

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