A New Exhaustive Method and Strategy for Finding Motifs in ChIP-Enriched Regions

ChIP-seq, which combines chromatin immunoprecipitation (ChIP) with next-generation parallel sequencing, allows for the genome-wide identification of protein-DNA interactions. This technology poses new challenges for the development of novel motif-finding algorithms and methods for determining exact protein-DNA binding sites from ChIP-enriched sequencing data. State-of-the-art heuristic, exhaustive search algorithms have limited application for the identification of short ([Image: see text], [Image: see text]) motifs ([Image: see text], [Image: see text]) contained in ChIP-enriched regions. In this work we have developed a more powerful exhaustive method (FMotif) for finding long ([Image: see text], [Image: see text]) motifs in DNA sequences. In conjunction with our method, we have adopted a simple ChIP-enriched sampling strategy for finding these motifs in large-scale ChIP-enriched regions. Empirical studies on synthetic samples and applications using several ChIP data sets including 16 TF (transcription factor) ChIP-seq data sets and five TF ChIP-exo data sets have demonstrated that our proposed method is capable of finding these motifs with high efficiency and accuracy. The source code for FMotif is available at http://211.71.76.45/FMotif/.