title: Analysis of computational footprinting methods for DNase sequencing experiments.
abstract: DNase-seq allows nucleotide-level identification of transcription factor binding sites on the basis of a computational search of footprint-like DNase I cleavage patterns on the DNA. Frequently in high-throughput methods, experimental artifacts such as DNase I cleavage bias affect the computational analysis of DNase-seq experiments. Here we performed a comprehensive and systematic study on the performance of computational footprinting methods. We evaluated ten footprinting methods in a panel of DNase-seq experiments for their ability to recover cell-specific transcription factor binding sites. We show that three methods--HINT, DNase2TF and PIQ--consistently outperformed the other evaluated methods and that correcting the DNase-seq signal for experimental artifacts significantly improved the accuracy of computational footprints. We also propose a score that can be used to detect footprints arising from transcription factors with potentially short residence times.
authors.affiliation: IZKF Computational Biology Research Group, RWTH Aachen University Medical School, Aachen, Germany.|Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.
authors.forename: Eduardo G
authors.identifier: http://orcid.org/0000-0001-7461-1443
authors.initials: EG
authors.lastname: Gusmao
authors.affiliation: IZKF Computational Biology Research Group, RWTH Aachen University Medical School, Aachen, Germany.|Aachen Institute for Advanced Study in Computational Engineering Science (AICES), RWTH Aachen University, Aachen, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Allhoff
authors.affiliation: Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.affiliation: IZKF Computational Biology Research Group, RWTH Aachen University Medical School, Aachen, Germany.|Department of Cell Biology, Institute of Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany.|Aachen Institute for Advanced Study in Computational Engineering Science (AICES), RWTH Aachen University, Aachen, Germany.
authors.forename: Ivan G
authors.initials: IG
authors.lastname: Costa
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology / Q000379:methods*; D018983:DNA Footprinting / Q000379:methods*; D003850:Deoxyribonuclease I / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D020014:K562 Cells; D011485:Protein Binding; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; D014157:Transcription Factors; D003850:Deoxyribonuclease I