title: Design and bioinformatics analysis of genome-wide CLIP experiments.
abstract: The past decades have witnessed a surge of discoveries revealing RNA regulation as a central player in cellular processes. RNAs are regulated by RNA-binding proteins (RBPs) at all post-transcriptional stages, including splicing, transportation, stabilization and translation. Defects in the functions of these RBPs underlie a broad spectrum of human pathologies. Systematic identification of RBP functional targets is among the key biomedical research questions and provides a new direction for drug discovery. The advent of cross-linking immunoprecipitation coupled with high-throughput sequencing (genome-wide CLIP) technology has recently enabled the investigation of genome-wide RBP-RNA binding at single base-pair resolution. This technology has evolved through the development of three distinct versions: HITS-CLIP, PAR-CLIP and iCLIP. Meanwhile, numerous bioinformatics pipelines for handling the genome-wide CLIP data have also been developed. In this review, we discuss the genome-wide CLIP technology and focus on bioinformatics analysis. Specifically, we compare the strengths and weaknesses, as well as the scopes, of various bioinformatics tools. To assist readers in choosing optimal procedures for their analysis, we also review experimental design and procedures that affect bioinformatics analyses.
authors.affiliation: Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Biological Sciences, Center for Systems Biology, The University of Texas at Dallas, Richardson, TX 75080, USA Bioinformatics Division, Center for Synthetic and System Biology, TNLIST, Tsinghua University, Beijing 100084, China.
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Corey
authors.affiliation: Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA yang.xie@utsouthwestern.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
mesh_terms: D030561:Databases, Nucleic Acid; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D047468:Immunoprecipitation; D059372:Nucleotide Motifs; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D017423:Sequence Analysis, RNA / Q000379:methods*; D012984:Software
chemical_list: D016601:RNA-Binding Proteins; D012313:RNA