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.