RT Journal Article
SR Electronic
T1 Combined analysis of genome sequencing and RNA-motifs reveals novel damaging non-coding mutations in human tumors
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 200188
DO 10.1101/200188
A1 Babita Singh
A1 Juan L. Trincado
A1 PJ Tatlow
A1 Stephen R. Piccolo
A1 Eduardo Eyras
YR 2018
UL http://biorxiv.org/content/early/2018/01/24/200188.abstract
AB A major challenge in cancer research is to determine the biological and clinical significance of somatic mutations in non-coding regions. This has been studied in terms of recurrence, functional impact, and association to individual regulatory sites, but the combinatorial contribution of mutations to common RNA regulatory motifs has not been explored. We developed a new method, MIRA, to perform the first comprehensive study of significantly mutated regions (SMRs) affecting binding sites for RNA-binding proteins (RBPs) in cancer. Extracting signals related to RNA-related selection processes and using RNA sequencing data from the same samples we identified alterations in RNA expression and splicing linked to mutations on RBP binding sites. We found SRSF10 and MBNL1 motifs in introns, HNRPLL motifs at 5’ UTRs, as well as 5’ and 3’ splice-site motifs, among others, with specific mutational patterns that disrupt the motif and impact RNA processing. MIRA facilitates the integrative analysis of multiple genome sites that operate collectively through common RBPs and can aid in the interpretation of non-coding variants in cancer. MIRA is available at https://github.com/comprna/mira.SMRsignificantly mutated regionNB-scoreNucleotide-bias scoreRBPRNA binding proteinRNA-seqRNA sequencing;