title: PeakXus: comprehensive transcription factor binding site discovery from ChIP-Nexus and ChIP-Exo experiments.
abstract: Transcription factor (TF) binding can be studied accurately in vivo with ChIP-exo and ChIP-Nexus experiments. Only fraction of TF binding mechanisms are yet fully understood and accurate knowledge of binding locations and patterns of TFs is key to understanding binding that is not explained by simple positional weight matrix models. ChIP-exo/Nexus experiments can also offer insight on the effect of single nucleotide polymorphism (SNP) at TF binding sites on expression of the target genes. This is an important mechanism of action for disease-causing SNPs at non-coding genomic regions.
  
  
  
  We describe a peak caller PeakXus that is specifically designed to leverage the increased resolution of ChIP-exo/Nexus and developed with the aim of making as few assumptions of the data as possible to allow discoveries of novel binding patterns. We apply PeakXus to ChIP-Nexus and ChIP-exo experiments performed both in Homo sapiens and in Drosophila melanogaster cell lines. We show that PeakXus consistently finds more peaks overlapping with a TF-specific recognition sequence than published methods. As an application example we demonstrate how PeakXus can be coupled with unique molecular identifiers (UMIs) to measure the effect of a SNP overlapping with a TF binding site on the in vivo binding of the TF.
  
  
  
  Source code of PeakXus is available at https://github.com/hartonen/PeakXus
  
  
  
  tuomo.hartonen@helsinki.fi or jussi.taipale@ki.se.
authors: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors: Tuomo
authors: T
authors: Hartonen
authors: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors: Biswajyoti
authors: B
authors: Sahu
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors: Kashyap
authors: K
authors: Dave
authors: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors: Teemu
authors: T
authors: Kivioja
authors: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors: Jussi
authors: J
authors: Taipale
mesh_terms: D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D003198:Computer Simulation; D004331:Drosophila melanogaster; D020869:Gene Expression Profiling; D056426:Genetic Loci; D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017422:Sequence Analysis, DNA; D014157:Transcription Factors
chemical_list: D014157:Transcription Factors