Improved detection of aberrant splicing using 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 for aberrant splicing detection that outperformed alternative approaches. However, as 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 alternative donor, alternative acceptor, and intron retention signal into a single value. Moreover, we optimized model parameters and filter cutoffs using candidate rare splice-disrupting variants as independent evidence. On 16,213 GTEx samples, our improved algorithm called typically 10 times fewer splicing outliers while increasing the proportio

SUBMITTER: Scheller IF 

PROVIDER: S-EPMC10104204 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature