DNA Motif Match Statistics Without Poisson Approximation

Transcription factors (TFs) play a crucial role in gene regulation by binding to specific regulatory sequences. The sequence motifs recognized by a TF can be described in terms of position frequency matrices. Searching for motif matches with a given position frequency matrix is achieved by employing a predefined score cutoff and subsequently counting the number of matches above this cutoff. In this article, we approximate the distribution of the number of motif matches based on a novel dynamic programming approach, which accounts for higher order sequence background (e.g., as is characteristic for CpG islands) and overlapping motif matches on both DNA strands. A comparison with our previously published compound Poisson approximation and a binomial approximation demonstrates that in particular for relaxed score thresholds, the dynamic programming approach yields more accurate results