Computational Tools for Splicing Defect Prediction in Breast/Ovarian Cancer Genes: How Efficient Are They at Predicting RNA Alterations?

Frontiers in Genetics
Alejandro Moles-FernándezSara Gutiérrez-Enríquez

Abstract

In silico tools for splicing defect prediction have a key role to assess the impact of variants of uncertain significance. Our aim was to evaluate the performance of a set of commonly used splicing in silico tools comparing the predictions against RNA in vitro results. This was done for natural splice sites of clinically relevant genes in hereditary breast/ovarian cancer (HBOC) and Lynch syndrome. A study divided into two stages was used to evaluate SSF-like, MaxEntScan, NNSplice, HSF, SPANR, and dbscSNV tools. A discovery dataset of 99 variants with unequivocal results of RNA in vitro studies, located in the 10 exonic and 20 intronic nucleotides adjacent to exon-intron boundaries of BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, ATM, BRIP1, CDH1, PALB2, PTEN, RAD51D, STK11, and TP53, was collected from four Spanish cancer genetic laboratories. The best stand-alone predictors or combinations were validated with a set of 346 variants in the same genes with clear splicing outcomes reported in the literature. Sensitivity, specificity, accuracy, negative predictive value (NPV) and Mathews Coefficient Correlation (MCC) scores were used to measure the performance. The discovery stage showed that HSF and SSF-like were the most accurate for var...Continue Reading

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Citations

Mar 31, 2019·International Journal of Cancer. Journal International Du Cancer·Lídia FeliubadalóUNKNOWN Catalan Hereditary Cancer Group
Feb 14, 2019·Human Genomics·Xin-Ying TangJian-Min Chen
Jan 26, 2020·International Journal of Molecular Sciences·Matteo AccetturoAlessandro Stella
Jun 14, 2019·Frontiers in Genetics·Eugenia Fraile-BethencourtEladio A Velasco
Oct 1, 2020·Computational and Structural Biotechnology Journal·Zodwa DlaminiRahaba Marima
Feb 19, 2021·Human Mutation·Yael GoldbergEitan Friedman
Nov 20, 2020·Molecular Therapy. Methods & Clinical Development·Mike BroedersW W M Pim Pijnappel
May 3, 2021·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Sabrina Samad ShoilyAbu Ashfaqur Sajib
May 5, 2021·Human Mutation·Tabea V RiepePeter A C 't Hoen
Dec 1, 2021·The Journal of Pathology·Alberto Valenzuela-PalomoEladio A Velasco
Dec 20, 2021·Human Mutation·Jacopo BoniBarbara Rivera

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Methods Mentioned

BETA
electrophoresis
ESRseq

Software Mentioned

like
PRIORS
dbscSNV
VarAFT
GeneSplicer
SPICE
MaxEntScan ( MES )
Visual Alamut
ESRseq
SPANR

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