Identification of transcription factor binding sites from ChIP-seq data at high-resolution
MOTIVATION: Chromatin-immunoprecipitation coupled to next-generation sequencing (ChIP-seq) is widely used to study the in vivo binding sites of transcription factors (TFs) and their regulatory targets. Recent improvements to ChIP-seq, such as increased resolution, promise deeper insights into transcriptional regulation, yet require novel computational tools to fully leverage their advantages.
RESULTS: To this aim, we have developed peakzilla, which can identify closely spaced TF binding sites at high resolution (i.e. resolves individual binding sites even if spaced closely), as we demonstrate using semi-synthetic datasets, performing ChIP-seq for the TF Twist in Drosophila embryos with different experimental fragment sizes, and analyzing ChIP-exo datasets. We show that the increased resolution reached by peakzilla is highly relevant as closely spaced Twist binding sites are strongly enriched in transcriptional enhancers, suggesting a signature to discriminate functional from abundant non-functional or neutral TF binding. Peakzilla is easy to use as it estimates all the necessary parameters from the data and is freely available.
Bardet AF, Steinmann J, Bafna S, Knoblich JA, Zeitlinger J, Stark A. Identification of transcription factor binding sites from ChIP-seq data at high-resolution. Bioinformatics. 2013 Aug 24. [Epub ahead of print]. Pubmed 23980024.