Genome-wide protein–DNA mapping studies have produced thousands of enriched sequence motifs, many of which are redundant because transcription factors (TFs) bind cooperatively as distinct complexes to shared sites. Here, we present Genomic CLustered Alignment of Motif Profiles (GenoCLAMP), an algorithm that unifies motif-clustering and alignment to collapse redundant motifs into high-quality merged matrix representations. We demonstrate that GenoCLAMP reliably recovers known TF complexes that bind common motifs and uncovers evidence for previously uncharacterized motifs. These results establish GenoCLAMP as a robust and efficient framework for motif consolidation, enhancing computational analyses and biological interpretation of large-scale TF–DNA binding datasets.
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