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The ability to perform de novo-based analysis of ChIP-Seq data opens the door to several possibilities. These include: (1) comparison of binding motifs for mutated versus wild-type transcription factors; and (2) motif evolution analysis in developmental studies, for species that have not been fully sequenced. It also enables researchers to analyze data from studies in which we may expect the genome being analyzed to diverge from the reference genome for that species.
(Heet al., 2015) De novo ChIP-seq analysis. Genome Biol.