Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA View Full Text


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Article Info

DATE

2019-03-22

AUTHORS

Ei-Wen Yang, Jae Hoon Bahn, Esther Yun-Hua Hsiao, Boon Xin Tan, Yiwei Sun, Ting Fu, Bo Zhou, Eric L. Van Nostrand, Gabriel A. Pratt, Peter Freese, Xintao Wei, Giovanni Quinones-Valdez, Alexander E. Urban, Brenton R. Graveley, Christopher B. Burge, Gene W. Yeo, Xinshu Xiao

ABSTRACT

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. More... »

PAGES

1338

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-09292-w

    DOI

    http://dx.doi.org/10.1038/s41467-019-09292-w

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112943518

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30902979


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