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Fig. 2 | Genome Biology

Fig. 2

From: MMSplice: modular modeling improves the predictions of genetic variant effects on splicing

Fig. 2

MMSplice improves the prediction of variant effect on exon skipping. a Schema of the Vex-seq experiment [29]. The effect of 2059 ExAC variants (red star) from or adjacent to 110 alternative exons were tested with reporter genes by measuring percent splice-in of the reference sequence (Ψref) and of the alternative (Ψalt) by RNAseq. bd Measured (y-axis) versus predicted (x-axis) Ψ differences between alternative and reference sequence for MMSplice (b), HAL [18] (c), and SPANR [17] (d) on Vex-seq test data. Color scale represents counts in hexagonal bins. The black line marks the y=x diagonal. Each plot is shown with the subset of variants that the considered model can score. Pearson correlations (R) and root-mean-square errors (RMSE) were also calculated based on the scored variants. The 95% confidence intervals for these two metrics were calculated with bootstrap (“Methods” section). (e) Schema of MFASS experiment [34]. Exon skipping effects of 27,733 ExAC SNVs (red star) spanning or adjacent to 2339 exons were tested by genome integration of designed construct. Splice-disrupting variant (SDV) is defined as a variant that change an exon with original exon inclusion index \(\geqslant 0.5\) by at least 0.5. f Precision-recall curve of MFASS SDV classification based on model predicted ΔΨ. Precision-recall curve for all three models was calculated for the sets of variants they can score. MMSplice (black) scored all 27,733 variants, SPANR (yellow) scored 27,663 variants (1,048 SDVs), and HAL (blue) scored 14,353 variants (489 SDVs)

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