Data Science Issues in Studying Protein–RNA Interactions with CLIP Technologies

2018/05/04 by Anob M. Chakrabarti, Nejc Haberman, Arne Praznik +2 · 2 citations
Biochemistry, Genetics and Molecular Biology · #RNA Research and Splicing #RNA and protein synthesis mechanisms #RNA modifications and cancer #RNA #Computational biology #RNA-binding protein #Immunoprecipitation #Visualization #Computer science #Biology #Protein–protein interaction #Data mining #Cell biology #Genetics #Gene

paper · pdf · doi:10.1146/annurev-biodatasci-080917-013525

openalex publication_date 2018/05/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

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.

Citations

• Recursive splicing in long vertebrate genes
• Transcriptome-wide Identification of RNA-Binding Protein and MicroRNA Target Sites by PAR-CLIP
• Measuring reproducibility of high-throughput experiments
• iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution
• Direct Competition between hnRNP C and U2AF65 Protects the Transcriptome from the Exonization of Alu Elements
• Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP)
• Computational analysis of CLIP-seq data
• A subcellular map of the human proteome
• A large-scale binding and functional map of human RNA-binding proteins

Cited by

• CLIP and complementary methods
• Cross-linking immunoprecipitation [wikipedia]

Related

• CLIP (Cross-Linking and Immunoprecipitation) Identification of RNAs Bound by a Specific Protein
• Analysis of Protein–RNA Interactions with Single‐Nucleotide Resolution Using iCLIP and Next‐Generation Sequencing
• Analysis of CLIP and iCLIP methods for nucleotide-resolution studies of protein-RNA interactions
• Positional motif analysis reveals the extent of specificity of protein-RNA interactions observed by CLIP
• HITS‐CLIP: panoramic views of protein–RNA regulation in living cells