Abstract
BackgroundBranch points (BPs) map within short motifs upstream of acceptor splice sites (3’ss) and are essential for splicing of pre-mature mRNA. Several BP-dedicated bioinformatics tools, including HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR and RNABPS were developed during the last decade. Here, we evaluated their capability to detect the position of BPs, and also to predict the impact on splicing of variants occurring upstream of 3’ss.ResultsWe used a large set of constitutive and alternative human 3’ss collected from Ensembl (n = 264,787 3’ss) and from in-house RNAseq experiments (n = 51,986 3’ss). We also gathered an unprecedented collection of functional splicing data for 120 variants (62 unpublished) occurring in BP areas of disease-causing genes. Branchpointer showed the best performance to detect the relevant BPs upstream of constitutive and alternative 3’ss (99.48 and 65.84% accuracies, respectively). For variants occurring in a BP area, BPP emerged as having the best performance to predict effects on mRNA splicing, with an accuracy of 89.17%.ConclusionsOur investigations revealed that Branchpointer was optimal to detect BPs upstream of 3’ss, and that BPP was most relevant to predict splicing alteration due to variants in the BP area.
Highlights
Branch points (BPs) map within short motifs upstream of acceptor splice sites (3’ss) and are essential for splicing of pre-mature Ribonucleic acids (RNA) messenger (mRNA)
The running times showed that Branch Point Prediction (BPP) is one of the faster tools and Branchpointer one of the slower tools (Additional file 1: Figure S3)
Showed the best performance with an accuracy of 99.48%. This highlighted the interest of the machine learning approach compared to support vector machine and mixture models used in the development of SVM-BPfinder and BPP, respectively
Summary
Branch points (BPs) map within short motifs upstream of acceptor splice sites (3’ss) and are essential for splicing of pre-mature mRNA. Several BP-dedicated bioinformatics tools, including HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR and RNABPS were developed during the last decade. We evaluated their capability to detect the position of BPs, and to predict the impact on splicing of variants occurring upstream of 3’ss. Splicing plays a crucial role for protein diversity in eukaryotic cells [1] This process, named alternative splicing, produces several mRNA molecules from a single pre-mRNA molecule and concerns approximately 95% of human genes [2]. The 3’OH of the 5′ exon attacks the downstream 3’ss thereby releasing the intronic lariat and joining the two exons together
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
