Reproducible inference of transcription factor footprints in ATAC-seq and DNase-seq datasets using protocol-specific bias modeling

Genome Biology
Aslıhan Karabacak CalvielloUwe Ohler

Abstract

DNase-seq and ATAC-seq are broadly used methods to assay open chromatin regions genome-wide. The single nucleotide resolution of DNase-seq has been further exploited to infer transcription factor binding sites (TFBSs) in regulatory regions through footprinting. Recent studies have demonstrated the sequence bias of DNase I and its adverse effects on footprinting efficiency. However, footprinting and the impact of sequence bias have not been extensively studied for ATAC-seq. Here, we undertake a systematic comparison of the two methods and show that a modification to the ATAC-seq protocol increases its yield and its agreement with DNase-seq data from the same cell line. We demonstrate that the two methods have distinct sequence biases and correct for these protocol-specific biases when performing footprinting. Despite the differences in footprint shapes, the locations of the inferred footprints in ATAC-seq and DNase-seq are largely concordant. However, the protocol-specific sequence biases in conjunction with the sequence content of TFBSs impact the discrimination of footprint from the background, which leads to one method outperforming the other for some TFs. Finally, we address the depth required for reproducible identification...Continue Reading

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Citations

Jun 12, 2019·Genes·Kate MegquierElinor K Karlsson
Oct 5, 2019·Nucleic Acids Research·Karl J V NordströmJörn Walter
May 22, 2019·Scientific Data·Chuanyu LiuLongqi Liu
Jun 6, 2019·Epigenetics & Chromatin·Kyu-Seon OhMyong-Hee Sung
Jun 17, 2020·Current Protocols in Human Genetics·Jason P Smith, Nathan C Sheffield
Sep 23, 2020·Genome Génome / Conseil National De Recherches Canada·Ian C TobiasJennifer A Mitchell
Dec 9, 2020·Molecular Cell·Can SönmezerArnaud Regis Krebs
Dec 29, 2020·Frontiers in Genetics·Óscar M LezcanoElena Gómez-Díaz
Apr 20, 2021·Nucleic Acids Research·Charbel AlfeghalySylvain Maenner
May 9, 2021·Genome Biology·Jiazhen ShenShankar Balasubramanian
Jun 20, 2021·Molecular Cell·Kristina ŽumerPatrick Cramer
May 18, 2021·Nucleic Acids Research·Shengquan ChenRui Jiang

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Methods Mentioned

BETA
footprinting
ATAC-seq
ChIP-seq
PCR

Software Mentioned

preseq
ENCODE
JAMM
SpeakerScan Toolset
ATAC
Roadmap Epigenomics
seqOutBias
bowtie2
SAM
seq

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