title: Differential peak calling of ChIP-seq signals with replicates with THOR.
abstract: The study of changes in protein-DNA interactions measured by ChIP-seq on dynamic systems, such as cell differentiation, response to treatments or the comparison of healthy and diseased individuals, is still an open challenge. There are few computational methods comparing changes in ChIP-seq signals with replicates. Moreover, none of these previous approaches addresses ChIP-seq specific experimental artefacts arising from studies with biological replicates. We propose THOR, a Hidden Markov Model based approach, to detect differential peaks between pairs of biological conditions with replicates. THOR provides all pre- and post-processing steps required in ChIP-seq analyses. Moreover, we propose a novel normalization approach based on housekeeping genes to deal with cases where replicates have distinct signal-to-noise ratios. To evaluate differential peak calling methods, we delineate a methodology using both biological and simulated data. This includes an evaluation procedure that associates differential peaks with changes in gene expression as well as histone modifications close to these peaks. We evaluate THOR and seven competing methods on data sets with distinct characteristics from in vitro studies with technical replicates to clinical studies of cancer patients. Our evaluation analysis comprises of 13 comparisons between pairs of biological conditions. We show that THOR performs best in all scenarios.
authors.affiliation: IZKF Bioinformatics Research Group, RWTH Aachen University Medical School, Pauwelsstr. 19, 52074 Aachen, Germany.|Aachen Institute for Advanced Study in Computational Engineering Science (AICES), RWTH Aachen University, Schinkelstr. 2, 52062 Aachen, Germany.|Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstr. 20, 52074 Aachen, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Allhoff
authors.affiliation: Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstr. 20, 52074 Aachen, Germany.|Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Pauwelstr. 30, 52074 Aachen, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Seré
authors.affiliation: IZKF Bioinformatics Research Group, RWTH Aachen University Medical School, Pauwelsstr. 19, 52074 Aachen, Germany.|Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstr. 20, 52074 Aachen, Germany.|Statistics Department, Federal University of Paraiba, Cidade Universitária, 58059-900, João Pessoa, PB, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: F Pires
authors.affiliation: Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstr. 20, 52074 Aachen, Germany.|Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Medical School, Pauwelstr. 30, 52074 Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.affiliation: IZKF Bioinformatics Research Group, RWTH Aachen University Medical School, Pauwelsstr. 19, 52074 Aachen, Germany ivan.costa@rwth-aachen.de.|Aachen Institute for Advanced Study in Computational Engineering Science (AICES), RWTH Aachen University, Schinkelstr. 2, 52062 Aachen, Germany.|Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstr. 20, 52074 Aachen, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: G Costa
mesh_terms: D000465:Algorithms; D002454:Cell Differentiation / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology / Q000379:methods*; D066264:Datasets as Topic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D044127:Epigenesis, Genetic; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics; D008390:Markov Chains; D017422:Sequence Analysis, DNA; D057188:Workflow
chemical_list: D006657:Histones