Leveraging cross-link modification events in CLIP-seq for motif discovery

Emad Bahrami-Samani, Luiz O.F. Penalva, Andrew D. Smith, Philip J. Uren

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

High-throughput protein-RNA interaction data generated by CLIP-seq has provided an unprecedented depth of access to the activities of RNA-binding proteins (RBPs), the key players in co-and post-transcriptional regulation of gene expression. Motif discovery forms part of the necessary follow-up data analysis for CLIP-seq, both to refine the exact locations of RBP binding sites, and to characterize them. The specific properties of RBP binding sites, and the CLIP-seq methods, provide additional information not usually present in the classic motif discovery problem: the binding site structure, and cross-linking induced events in reads. We show that CLIP-seq data contains clear secondary structure signals, as well as technology-and RBP-specific cross-link signals. We introduce Zagros, a motif discovery algorithm specifically designed to leverage this information and explore its impact on the quality of recovered motifs. Our results indicate that using both secondary structure and cross-link modifications can greatly improve motif discovery on CLIP-seq data. Further, the motifs we recover provide insight into the balance between sequence-and structure-specificity struck by RBP binding.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalNucleic acids research
Volume43
Issue number1
DOIs
StatePublished - Sep 1 2015

ASJC Scopus subject areas

  • Genetics

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