Improved ESE/ESS Predictions

The HSF professional expert system is now using a new algorithm to predict the impact of mutations on auxiliary splicing sequences (ESE/ESS). To do so, it now takes into account the global impact on both signals and only mutations significantly disturbing the balance between positive and negative signals are considered.

Left: Normal situation for an exon with a majority of Exonic Splicing Enhancers (ESE) that favour the exon recognition by the spliceosome.

Right: an exonic mutation may significantly alter the ESE/ESS ratio by removing ESE, creating ESS or both. The exon recognition is now hampered by the new ratio in favour of ESS.

To evaluate this new algorithm, we used a dataset of 27 exonic mutations that alter splicing as demonstrated by minigene assays. Twenty three out of the 27 exonic mutations were accurately predicted to impact (11/14) or not (12/13) intronic splicing, resulting in a 85.2% accuracy, a 92% specificity and a 79% sensitivity strongly outperforming previous detection algorithms.

Minigene effect: Yes = the splicing is altered by the mutation; No = the splicing is not altered by the mutation; Yes* = no impact on auxiliary splicing motifs ratio but activation of a cryptic donor splice site.

HSF Professional: Yes = the ESE/ESS ratio is predicted to be significantly altered by the mutation; No = the ESE/ESS ratio is predicted to be not significantly altered by the mutation.

© 2020, Genomnis