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bioRxiv · 10.1101/2022.07.30.502132

SpliceAI-10k calculator for the prediction of pseudoexonization, intron retention, and exon deletion

Canson, D. M.·Kondrashova, O. M.·de la Hoya, M.·Parsons, M. T.·Glubb, D. M.·Spurdle, A. B.
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Abstract

SummarySpliceAI is a widely used splicing prediction tool and its most common application relies on the maximum delta score to assign variant impact on splicing. We developed the SpliceAI-10k calculator (SAI-10k-calc) to extend use of this tool to predict: the splicing aberration type including pseudoexonization, intron retention, partial exon deletion, and (multi)exon skipping using a 10 kb analysis window; the size of inserted or deleted sequence; the effect on reading frame; and the altered amino acid sequence. SAI-10k-calc has 95% sensitivity and 96% specificity for predicting variants that impact splicing, computed from a control dataset of 1,212 single nucleotide variants (SNVs) with curated splicing assay results. Notably, it has high performance ([≥]84% accuracy) for predicting pseudoexon and partial intron retention. The automated amino acid sequence prediction allows for efficient identification of variants that are expected to result in mRNA nonsense-mediated decay or translation of truncated proteins. Availability and implementationSAI-10k-calc is implemented in R (https://github.com/adavi4/SAI-10k-calc) and also available as a Microsoft Excel spreadsheet. Users can adjust the default thresholds to suit their target performance values. Supplementary informationSupplementary data are available online.

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Canson, D. M., Kondrashova, O. M., de la Hoya, M., Parsons, M. T., Glubb, D. M., Spurdle, A. B.. 2022-08-01. SpliceAI-10k calculator for the prediction of pseudoexonization, intron retention, and exon deletion. https://doi.org/10.1101/2022.07.30.502132

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