Fig. 4: Predicting tissue-specific splicing alterations on all ClinVar variants.

a The strategy to derive tissue specificity variants from model prediction. We created a reference set of common splicing sites to derive background distribution and calculate tissue-specific z-scores for new variants in order to make fair comparisons across tissues, and gene enrichment is calculated based on tissue-specific splice-altering SNVs. b Top five genes enriched for tissue-specific splice-altering SNVs for each of the 15 tissues as predicted by SpTransformer. The size of the bubbles represents the number of SNVs in each gene, and the color of the bubbles represents the significant level of enrichment, one-sided hypergeometric test was used for statistics. We manually examined genes associated with tissue-specific phenotypes from the HPO database and marked by a black rectangle box. c Expression pattern of top 3 genes in enrichment result of each tissue. d Proportion of pathogenic SNVs predicted as tissue-specific splice altering in different tissues. Only genes that have a p-value < 0.05 in enrichment were included. The box extends from the first quartile to the third quartile of the data, with a line at the median. The dashed line represents the median proportions of SNVs in each tissue. e Number of tissue-specific splice-altering SNVs grouped by pathogenic classifications on TTN gene in different tissues. f Genome coordinate and Tissue z-score of SNVs on a sub-region of TTN gene. SNVs are labeled with ClinVar annotation. Panel a, created with BioRender.com, was released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.