RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins.
Post-transcriptional regulation
RNA-binding protein
Variant functional impact
Variant prioritization
Journal
Genome biology
ISSN: 1474-760X
Titre abrégé: Genome Biol
Pays: England
ID NLM: 100960660
Informations de publication
Date de publication:
30 07 2020
30 07 2020
Historique:
received:
03
01
2018
accepted:
28
02
2020
entrez:
31
7
2020
pubmed:
31
7
2020
medline:
7
7
2021
Statut:
epublish
Résumé
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, which cannot be found by most current prioritization methods, for example, variants affecting splicing.
Identifiants
pubmed: 32727537
doi: 10.1186/s13059-020-01979-4
pii: 10.1186/s13059-020-01979-4
pmc: PMC7391703
doi:
Substances chimiques
RNA-Binding Proteins
0
Types de publication
Evaluation Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
151Subventions
Organisme : NIMH NIH HHS
ID : U01 MH116492
Pays : United States
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