Motif discovery and motif finding from genome-mapped DNase footprint data

Motif discovery and motif finding from genome-mapped DNase footprint data - Motivation: Footprint data is an important source of information on transcription factor recognition motifs. However, a footprinting fragment can contain no sequences similar to known protein recognition sites. Inspection of genome fragments nearby can help to identify missing site positions.
Results: Genome fragments containing footprints were supplied to a pipeline that constructed a position weight matrix (PWM) for different motif lengths and selected the optimal PWM. Fragments were aligned with the SeSiMCMC sampler and a new heuristic algorithm, Bigfoot. Footprints with missing hits were found for ~50% of factors. Adding only 2 bp on both sides of a footprinting fragment recovered most hits. We automatically constructed motifs for 41 Drosophila factors. New motifs can recognize footprints with a greater sensitivity at the same false positive rate than existing models. Also we discuss possible overfitting of constructed motifs.
Availability: Software and the collection of regulatory motifs are freely available at http://line.imb.ac.ru/DMMPMM.
Supplementary information: http://line.imb.ac.ru/DMMPMM