Friday, September 5, 2014

Fwd: Differential motif enrichment analysis of paired ChIP-seq experiments

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Differential motif enrichment analysis of paired ChIP-seq experiments: "Background:
Motif enrichment analysis of transcription factor ChIP-seq data can help identify transcription factorsthat cooperate or compete. Previously, little attention has been given to comparative motif enrichmentanalysis of pairs of ChIP-seq experiments, where the binding of the same transcription factoris assayed under different conditions. Such comparative analysis could potentially identify the distinctregulatory partners/competitors of the assayed transcription factor under different conditions orat different stages of development.
Results:
We describe a new methodology for identifying sequence motifs that are differentially enriched inone set of DNA or RNA sequences relative to another set, and apply it to paired ChIP-seq experiments.We show that, using paired ChIP-seq data for a single transcription factor, differential motifenrichment analysis identifies all the known key transcription factors involved in the transformationof non-cancerous immortalized breast cells (MCF10A-ER-Src cells) into cancer stem cells whereasnon-differential motif enrichment analysis does not. We also show that differential motif enrichmentanalysis identifies regulatory motifs that are significantly enriched at constrained locations within thebound promoters, and that these motifs are not identified by non-differential motif enrichment analysis.Our methodology differs from other approaches in that it leverages both comparative enrichmentand positional enrichment of motifs in ChIP-seq peak regions or in the promoters of genes bound bythe transcription factor.
Conclusions:
We show that differential motif enrichment analysis of paired ChIP-seq experiments offers biologicalinsights not available from non-differential analysis. In contrast to previous approaches, our methoddetects motifs that are enriched in a constrained region in one set of sequences, but not enrichedin the same region in the comparative set. We have enhanced the web-based CentriMo algorithmto allow it to perform the constrained differential motif enrichment analysis described in this paper,and CentriMo's on-line interface (http://meme.ebi.edu.au) provides dozens of databases of DNA- andRNA-binding motifs from a full range of organisms. All data and output files presented here are available at http://research.imb.uq.edu.au/t.bailey/supplementary_data/Lesluyes2014."

(Via BMC Genomics - Latest Articles.)