HisTrader: A Tool to Identify Nucleosome Free Regions from ChIP-Seq of Histone Post-Translational Modifications

MotivationChromatin immuno-precipitation sequencing (ChIP-Seq) of histone post-translational modifications coupled with de novo motif elucidation and enrichment analyses can identify transcription factors responsible for orchestrating transitions between cell-and disease-states. However, the identified regulatory elements can span several kilobases (kb) in length, which complicates motif-based analyses. Restricting the length of the target DNA sequence(s) can reduce false positives. Therefore, we present HisTrader, a computational tool to identify the regions accessible to transcription factors, nucleosome free regions (NFRs), within histone modification peaks to reduce the DNA sequence length required for motif analyses. ResultsHisTrader accurately identifies NFRs from H3K27Ac ChIP-seq profiles of the lung cancer cell line A549, which are validated by the presence of DNaseI hypersensitivity. In addition, HisTrader reveals that multiple NFRs are common within individual regulatory elements; an easily overlooked feature that should be considered to improve sensitivity of motif analyses using histone modification ChIP-seq data. Availability and implementationThe HisTrader script is open-source and available on GitHub (https://github.com/SvenBaileyLab/Histrader) under a GNU general public license (GPLv3). HisTrader is written in PERL and can be run on any platform with PERL installed.