RT Journal Article
SR Electronic
T1 RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 474072
DO 10.1101/474072
A1 Zhang, Jing
A1 Liu, Jason
A1 Lee, Donghoon
A1 Feng, Jo-Jo
A1 Lochovsky, Lucas
A1 Lou, Shaoke
A1 Rutenberg-Schoenberg, Michael
A1 Gerstein, Mark
YR 2018
UL http://biorxiv.org/content/early/2018/11/19/474072.abstract
AB RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant-prioritization methods only focus on transcriptional regulation. Here, we integrate the portfolio of ENCODE-RBP experiments to develop RADAR, a variant-scoring framework. RADAR uses conservation, RNA structure, network centrality, and motifs to provide an overall impact score. Then it further incorporates tissue-specific inputs to highlight disease-specific variants. Our results demonstrate RADAR can successfully pinpoint variants, both somatic and germline, associated with RBP-function dysregulation, that cannot be found by most current prioritization methods, for example variants affecting splicing.RBPRNA binding Protein;ENCODEthe Encyclopedia of DNA Elements;PWMposition weight matrix;eCLIPenhanced crosslinking and immunoprecipitation;RADARRNA BinDing Protein regulome Annotation and pRioritization;UTRuntranslated regions;DAFderived allele frequency;RBNSRNA Bind-N-Seq.