Improved detection of aberrant splicing with FRASER 2.0 and the intron Jaccard index.

ABSTRACT: Detection of aberrantly spliced genes is an important step in RNA-seq-based rare-disease diagnostics. We recently developed FRASER, a denoising autoencoder-based method that outperformed alternative methods of detecting aberrant splicing. However, because FRASER's three splice metrics are partially redundant and tend to be sensitive to sequencing depth, we introduce here a more robust intron-excision metric, the intron Jaccard index, that combines the alternative donor, alternative acceptor, and intron-retention signal into a single value. Moreover, we optimized model parameters and filter cutoffs by using candidate rare-splice-disrupting variants as independent evidence. On 16,213 GTEx samples, our improved algorithm, FRASER 2.0, called typically 10 times fewer splicing outliers while inc

SUBMITTER: Scheller IF 

PROVIDER: S-EPMC10716352 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature