Prioritization model to identify SRE-disrupting variants for splicing analysis
While the current SRE-dedicated bioinformatic tools have significant limitations in terms of specificity, our results indicate that using a combination of tools can improve prediction and increase confidence in the selection of variants for confirmatory splicing assays. Drawing from the variant selection process (Figure 2), results relating to donor and acceptor splice site strength (Table 3), and the evaluation of SRE prediction tools (Table 4), we developed a generic workflow. This prioritization model uses MES for native and de novo splice site analysis, and HSF and ΔHZEI in series for SRE prediction, as summarized in Figure 4.