Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA
| Autor: | Peter Freese, Christopher B. Burge, Esther Yun-Hua Hsiao, Gabriel A. Pratt, Boon Xin Tan, Jae Hoon Bahn, Giovanni Quinones-Valdez, Xintao Wei, Ting Fu, Ei-Wen Yang, Brenton R. Graveley, Xinshu Xiao, Alexander E. Urban, Gene W. Yeo, Yiwei Sun, Bo Zhou, Eric L. Van Nostrand |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Messenger Amino Acid Motifs General Physics and Astronomy RNA-binding protein 02 engineering and technology Plasma protein binding 0302 clinical medicine Gene expression Disease lcsh:Science 3' Untranslated Regions Regulation of gene expression 0303 health sciences Multidisciplinary RNA-Binding Proteins Single Nucleotide Hep G2 Cells 021001 nanoscience & nanotechnology RNA splicing 0210 nano-technology RNA Helicases Protein Binding Immunoprecipitation Science 1.1 Normal biological development and functioning RNA Splicing Quantitative Trait Loci Single-nucleotide polymorphism Computational biology Biology ENCODE Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Underpinning research Genetics Humans Computer Simulation Genetic Predisposition to Disease RNA Messenger Polymorphism Binding site Allele Alleles 030304 developmental biology Genetic association Messenger RNA Base Sequence Human Genome RNA Computational Biology Genetic Variation Reproducibility of Results General Chemistry 030104 developmental biology Trans-Activators lcsh:Q Generic health relevance K562 Cells 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature communications, vol 10, iss 1 Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) |
| ISSN: | 2041-1723 |
| Popis: | Allele-specific protein-RNA binding is an essential aspect that may reveal functional genetic variants (GVs) mediating post-transcriptional regulation. Recently, genome-wide detection of in vivo binding of RNA-binding proteins is greatly facilitated by the enhanced crosslinking and immunoprecipitation (eCLIP) method. We developed a new computational approach, called BEAPR, to identify allele-specific binding (ASB) events in eCLIP-Seq data. BEAPR takes into account crosslinking-induced sequence propensity and variations between replicated experiments. Using simulated and actual data, we show that BEAPR largely outperforms often-used count analysis methods. Importantly, BEAPR overcomes the inherent overdispersion problem of these methods. Complemented by experimental validations, we demonstrate that the application of BEAPR to ENCODE eCLIP-Seq data of 154 proteins helps to predict functional GVs that alter splicing or mRNA abundance. Moreover, many GVs with ASB patterns have known disease relevance. Overall, BEAPR is an effective method that helps to address the outstanding challenge of functional interpretation of GVs. Differential binding of RNA-binding proteins mediated by genetic variants (GVs) can influence posttranscriptional regulation. Here, the authors develop BEAPR, a computational approach to identify allele-specific binding events in eCLIP-Seq data. |
| Databáze: | OpenAIRE |
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