Tuomo Hartonen1, Biswajyoti Sahu1, Kashyap Dave2, Teemu Kivioja1, Jussi Taipale3. 1. Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland. 2. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden. 3. Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Abstract
MOTIVATION: 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. RESULTS: 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. AVAILABILITY AND IMPLEMENTATION: Source code of PeakXus is available at https://github.com/hartonen/PeakXus CONTACT: tuomo.hartonen@helsinki.fi or jussi.taipale@ki.se.
MOTIVATION: 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. RESULTS: 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. AVAILABILITY AND IMPLEMENTATION: Source code of PeakXus is available at https://github.com/hartonen/PeakXus CONTACT: tuomo.hartonen@helsinki.fi or jussi.taipale@ki.se.
Authors: Jarkko Toivonen; Teemu Kivioja; Arttu Jolma; Yimeng Yin; Jussi Taipale; Esko Ukkonen Journal: Nucleic Acids Res Date: 2018-05-04 Impact factor: 16.971
Authors: Kimmo Palin; Esa Pitkänen; Mikko Turunen; Biswajyoti Sahu; Päivi Pihlajamaa; Teemu Kivioja; Eevi Kaasinen; Niko Välimäki; Ulrika A Hänninen; Tatiana Cajuso; Mervi Aavikko; Sari Tuupanen; Outi Kilpivaara; Linda van den Berg; Johanna Kondelin; Tomas Tanskanen; Riku Katainen; Marta Grau; Heli Rauanheimo; Roosa-Maria Plaketti; Aurora Taira; Päivi Sulo; Tuomo Hartonen; Kashyap Dave; Bernhard Schmierer; Sandeep Botla; Maria Sokolova; Anna Vähärautio; Kornelia Gladysz; Halit Ongen; Emmanouil Dermitzakis; Jesper Bertram Bramsen; Torben Falck Ørntoft; Claus Lindbjerg Andersen; Ari Ristimäki; Anna Lepistö; Laura Renkonen-Sinisalo; Jukka-Pekka Mecklin; Jussi Taipale; Lauri A Aaltonen Journal: Nat Commun Date: 2018-09-10 Impact factor: 14.919