Role of Splicing Regulatory Elements and In Silico Tools Usage in the Identification of Deep Intronic Splicing Variants in Hereditary Breast/Ovarian Cancer Genes.

ABSTRACT: The contribution of deep intronic splice-altering variants to hereditary breast and ovarian cancer (HBOC) is unknown. Current computational in silico tools to predict spliceogenic variants leading to pseudoexons have limited efficiency. We assessed the performance of the SpliceAI tool combined with ESRseq scores to identify spliceogenic deep intronic variants by affecting cryptic sites or splicing regulatory elements (SREs) using literature and experimental datasets. Our results with 233 published deep intronic variants showed that SpliceAI, with a 0.05 threshold, predicts spliceogenic deep intronic variants affecting cryptic splice sites, but is less effective in detecting those affecting SREs. Next, we characterized the SRE profiles using ESRseq, showing that pseudoexons are significantl

SUBMITTER: Moles-Fernandez A 

PROVIDER: S-EPMC8268271 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature