title: Leveraging cross-link modification events in CLIP-seq for motif discovery.
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.
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Emad
authors.initials: E
authors.lastname: Bahrami-Samani
authors.affiliation: Children's Cancer Research Institute and Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, USA.
authors.forename: Luiz O F
authors.initials: LO
authors.lastname: Penalva
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Smith
authors.affiliation: Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA uren@usc.edu.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Uren
mesh_terms: D020413:3' Untranslated Regions; D000465:Algorithms; D001665:Binding Sites; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D047468:Immunoprecipitation; D015233:Models, Statistical; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D020413:3' Untranslated Regions; D016601:RNA-Binding Proteins; D012313:RNA