  The interaction between proteins and DNA is a key driving force in a
significant number of biological processes such as transcriptional regulation,
repair, recombination, splicing, and DNA modification. The identification of
DNA-binding sites and the specificity of target proteins in binding to these
regions are two important steps in understanding the mechanisms of these
biological activities. A number of high-throughput technologies have recently
emerged that try to quantify the affinity between proteins and DNA motifs.
Despite their success, these technologies have their own limitations and fall
short in precise characterization of motifs, and as a result, require further
downstream analysis to extract useful and interpretable information from a
haystack of noisy and inaccurate data. Here we propose MotifMark, a new
algorithm based on graph theory and machine learning, that can find binding
sites on candidate probes and rank their specificity in regard to the
underlying transcription factor. We developed a pipeline to analyze
experimental data derived from compact universal protein binding microarrays
and benchmarked it against two of the most accurate motif search methods. Our
results indicate that MotifMark can be a viable alternative technique for
prediction of motif from protein binding microarrays and possibly other related
high-throughput techniques.
