Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants
Raphaël Leman
(1, 2)
,
Hélène Tubeuf
(2)
,
Sabine Raad
(2)
,
Isabelle Tournier
(2)
,
Céline Derambure
(2)
,
Raphaël Lanos
(2)
,
Pascaline Gaildrat
(2)
,
Gaia Castelain
(2)
,
Julie Hauchard
(2)
,
Audrey Killian
(2)
,
Stéphanie Baert-Desurmont
(2)
,
Angelina Legros
(1)
,
Nicolas Goardon
(2, 1)
,
Céline Quesnelle
(1)
,
Agathe Ricou
(2, 1)
,
Laurent Castera
(2, 1)
,
Dominique Vaur
(2, 1)
,
Gérald Le Gac
(3)
,
Chandran Ka
(3)
,
Yann Fichou
(3)
,
Françoise Bonnet-Dorion
(4, 5)
,
Nicolas Sevenet
(4, 5)
,
Marine Guillaud-Bataille
(6, 7)
,
Nadia Boutry-Kryza
(8)
,
Inès Schultz
(9)
,
Virginie Caux-Moncoutier
(10)
,
Maria Rossing
(11)
,
Logan Walker
(12)
,
Amanda Spurdle
(13)
,
Claude Houdayer
(2)
,
Alexandra Martins
(2)
,
Sophie Krieger
(1, 2)
1
UNICANCER/CRLC -
Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
2 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
3 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
4 VINCO - Validation et identification de nouvelles cibles en oncologie
5 Institut Bergonié [Bordeaux]
6 IGR - Institut Gustave Roussy
7 Génétique (Biologie pathologie)
8 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
9 CRLCC Paul Strauss - Centre Paul Strauss
10 Institut Curie [Paris]
11 UCPH - University of Copenhagen = Københavns Universitet
12 University of Otago [Dunedin, Nouvelle-Zélande]
13 QIMR Berghofer Medical Research Institute
2 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
3 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
4 VINCO - Validation et identification de nouvelles cibles en oncologie
5 Institut Bergonié [Bordeaux]
6 IGR - Institut Gustave Roussy
7 Génétique (Biologie pathologie)
8 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
9 CRLCC Paul Strauss - Centre Paul Strauss
10 Institut Curie [Paris]
11 UCPH - University of Copenhagen = Københavns Universitet
12 University of Otago [Dunedin, Nouvelle-Zélande]
13 QIMR Berghofer Medical Research Institute
Raphaël Leman
- Fonction : Auteur
- PersonId : 795793
- ORCID : 0000-0003-1978-7133
Yann Fichou
- Fonction : Auteur
- PersonId : 762899
- ORCID : 0000-0002-5104-9125
Résumé
Abstract Background 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. 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. Results We 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%. Conclusions Our 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.