Abstract
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.
Footnotes
Jing Zhang and Jason Liu are co-first authors.
List of abbreviations
- RBP
- RNA binding Protein;
- ENCODE
- the Encyclopedia of DNA Elements;
- PWM
- position weight matrix;
- eCLIP
- enhanced crosslinking and immunoprecipitation;
- RADAR
- RNA BinDing Protein regulome Annotation and pRioritization;
- UTR
- untranslated regions;
- DAF
- derived allele frequency;
- RBNS
- RNA Bind-N-Seq.