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.