Browsing by Subject "Intron"

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    RegSNPs-intron: a computational framework for predicting pathogenic impact of intronic single nucleotide variants
    (BMC, 2019-11-28) Lin, Hai; Hargreaves, Katherine A.; Li, Rudong; Reiter, Jill L.; Wang, Yue; Mort, Matthew; Cooper, David N.; Zhou, Yaoqi; Zhang, Chi; Eadon, Michael T.; Dolan, M. Eileen; Ipe, Joseph; Skaar, Todd C.; Liu, Yunlong; Medical and Molecular Genetics, School of Medicine
    Single nucleotide variants (SNVs) in intronic regions have yet to be systematically investigated for their disease-causing potential. Using known pathogenic and neutral intronic SNVs (iSNVs) as training data, we develop the RegSNPs-intron algorithm based on a random forest classifier that integrates RNA splicing, protein structure, and evolutionary conservation features. RegSNPs-intron showed excellent performance in evaluating the pathogenic impacts of iSNVs. Using a high-throughput functional reporter assay called ASSET-seq (ASsay for Splicing using ExonTrap and sequencing), we evaluate the impact of RegSNPs-intron predictions on splicing outcome. Together, RegSNPs-intron and ASSET-seq enable effective prioritization of iSNVs for disease pathogenesis.