Annual Review of Biomedical Data Science · 2018 · 76 citations · 89 references
Life SciencesData ScienceMolecular BiologyGene ExpressionGenomicsTranscriptomicsProtein-nucleic Acid InteractionsRna Quality ControlRna Sequencing AnalysisRna-binding ProteinsRna-protein InteractionsTranscript Sequence AnalysisCrosslinkingProtein-rna Binding Site PredictionProtein-rna Recognition MotifsRna Binding Protein RegulationRna Motif DiscoveryRna-binding Protein InteractionsRna-binding SpecificityUv Crosslinking
An interplay of experimental and computational methods is required to achieve a comprehensive understanding of protein-RNA interactions. UV crosslinking and immunoprecipitation (CLIP) identifies endogenous interactions by sequencing RNA fragments that copurify with a selected RNA-binding protein under stringent conditions. Here we focus on approaches for the analysis of the resulting data and appraise the methods for peak calling, visualization, analysis, and computational modeling of protein-RNA binding sites. We advocate that the sensitivity and specificity of data be assessed in combination for computational quality control. Moreover, we demonstrate the value of analyzing sequence motif enrichment in peaks assigned from CLIP data and of visualizing RNA maps, which examine the positional distribution of peaks around regulated landmarks in transcripts. We use these to assess how variations in CLIP data quality and in different peak calling methods affect the insights into regulatory mechanisms. We conclude by discussing future opportunities for the computational analysis of protein-RNA interaction experiments.
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A subcellular map of the human proteome
Peter Thul, Lovisa Åkesson, Mikaela Wiking et al. · Science · 2017 · 3K citations