Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA
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 immunoprecipitati...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2020
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| Online Access: | https://hdl.handle.net/1721.1/126514 |
| _version_ | 1811071262339891200 |
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| author | Yang, Ei-Wen Bahn, Jae Hoon Yun-Hua Hsiao, Esther Tan, Boon Xin Sun, Yiwei Fu, Ting Zhou, Bo Van Nostrand, Eric L. Pratt, Gabriel A. Freese, Peter Dale Wei, Xintao Quinones-Valdez, Giovanni Urban, Alexander E. Graveley, Brenton R. Burge, Christopher B Yeo, Gene W. Xiao, Xinshu |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Yang, Ei-Wen Bahn, Jae Hoon Yun-Hua Hsiao, Esther Tan, Boon Xin Sun, Yiwei Fu, Ting Zhou, Bo Van Nostrand, Eric L. Pratt, Gabriel A. Freese, Peter Dale Wei, Xintao Quinones-Valdez, Giovanni Urban, Alexander E. Graveley, Brenton R. Burge, Christopher B Yeo, Gene W. Xiao, Xinshu |
| author_sort | Yang, Ei-Wen |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:48:23Z |
| format | Article |
| id | mit-1721.1/126514 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:48:23Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1265142022-09-23T14:42:13Z Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA Yang, Ei-Wen Bahn, Jae Hoon Yun-Hua Hsiao, Esther Tan, Boon Xin Sun, Yiwei Fu, Ting Zhou, Bo Van Nostrand, Eric L. Pratt, Gabriel A. Freese, Peter Dale Wei, Xintao Quinones-Valdez, Giovanni Urban, Alexander E. Graveley, Brenton R. Burge, Christopher B Yeo, Gene W. Xiao, Xinshu Massachusetts Institute of Technology. Department of Biology 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. National Human Genome Research Institute (U.S.) (ENCODE Project, grant U01HG009417) National Human Genome Research Institute (U.S.) (ENCODE Project, grant U54HG007005) National Institutes of Health (U.S.) (NIH R01HG006264) National Institutes of Health (U.S.) (NIH R01AG056476) Damon Runyon Cancer Research Foundation (DRG-2172-13, Merck Fellow) National Institutes of Health (U.S.) (K99 grant from the NIH (HG009530)) National Science Foundation (U.S.) (GraduateResearch Fellowship) 2020-08-07T18:20:38Z 2020-08-07T18:20:38Z 2019-03 2019-07-18T13:58:45Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 https://hdl.handle.net/1721.1/126514 Yang, Ei-Wen, Jae Hoon Bahn, Esther Yun-Hua Hsiao et al. "Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA." Nature Communications, 10, Article number:1338 (2019), © 2019, The Author(s). https://dx.doi.org/10.1038/s41467-019-09292-w en https://dx.doi.org/10.1038/s41467-019-09292-w Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Nature Nature |
| spellingShingle | Yang, Ei-Wen Bahn, Jae Hoon Yun-Hua Hsiao, Esther Tan, Boon Xin Sun, Yiwei Fu, Ting Zhou, Bo Van Nostrand, Eric L. Pratt, Gabriel A. Freese, Peter Dale Wei, Xintao Quinones-Valdez, Giovanni Urban, Alexander E. Graveley, Brenton R. Burge, Christopher B Yeo, Gene W. Xiao, Xinshu Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA |
| title | Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA |
| title_full | Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA |
| title_fullStr | Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA |
| title_full_unstemmed | Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA |
| title_short | Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA |
| title_sort | allele specific binding of rna binding proteins reveals functional genetic variants in the rna |
| url | https://hdl.handle.net/1721.1/126514 |
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