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. 2023 Apr 3;39(4):btad179.
doi: 10.1093/bioinformatics/btad179.

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

Daffodil M Canson  1   2 , Aimee L Davidson  1 , Miguel de la Hoya  3 , Michael T Parsons  1 , Dylan M Glubb  2   4 , Olga Kondrashova  4 , Amanda B Spurdle  1   2
Affiliations

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

Daffodil M Canson et al. Bioinformatics. .

Abstract

Summary: SpliceAI 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 1212 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 implementation: SAI-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.

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Figures

Figure 1
Figure 1
Types of splicing aberrations predicted by the SpliceAI-10k calculator. Six SNVs that were experimentally confirmed to alter splicing are correctly predicted by SAI-10k-calc (A–F). Of these, two represent correct prediction of combinations of splicing aberration types (D, E). Amino acid sequence predictions include three amino acids preceding the first variant amino acid, followed by the modified sequence inside square brackets. In-frame deletions that do not introduce any missense amino acid change (example in panel E) are indicated by blank square brackets flanked by three wild type amino acids preceding and following the deleted sequence. In all cases, deleted amino acids are not shown
See this image and copyright information in PMC

References

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