PirePred: an accurate online consensus tool to interpret newborn screening–related genetic variants in structural context

Galano-Frutos, J. (Universidad de Zaragoza) ; García-Cebollada, H. (Universidad de Zaragoza) ; López, A. ; Rosell, M. ; de la Cruz, X. ; Fernández-Recio, J. ; Sancho, J. (Universidad de Zaragoza)

Resumen: PirePred is a genetic interpretation tool used for a variety of medical conditions investigated in newborn screening programs. The PirePred server retrieves, analyzes, and displays in real time genetic and structural data on 58 genes/proteins associated with medical conditions frequently investigated in the newborn. PirePred analyzes the predictions generated by 15 pathogenicity predictors and applies an optimized majority vote algorithm to classify any possible nonsynonymous single-nucleotide variant as pathogenic, benign, or of uncertain significance. PirePred predictions for variants of clear clinical significance are better than those of any of the individual predictors considered (based on accuracy, sensitivity, and negative predictive value) or are among the best ones (for positive predictive value and Matthews correlation coefficient). PirePred predictions also outperform the comparable in silico predictions offered as supporting evidence, according to American College of Medical Genetics and Genomics guidelines, by VarSome and Franklin. Also, PirePred has very high prediction coverage. To facilitate the molecular interpretation of the missense, nonsense, and frameshift variants in ClinVar, the changing amino acid residue is displayed in its structural context, which is analyzed to provide functional clues. PirePred is an accurate, robust, and easy-to-use tool for clinicians involved in neonatal screening programs and for researchers of related diseases. The server is freely accessible and provides a user-friendly gateway into the structural/functional consequences of genetic variants at the protein level. © 2022 Association for Molecular Pathology and American Society for Investigative Pathology

Idioma: Inglés

DOI: 10.1016/j.jmoldx.2022.01.005

Año: 2022

Publicado en: JOURNAL OF MOLECULAR DIAGNOSTICS 24, 4 (2022), 406-425
ISSN: 1525-1578

Factor impacto JCR: 4.1 (2022)

Categ. JCR: PATHOLOGY rank: 21 / 76 = 0.276 (2022) - Q2 - T1

Factor impacto CITESCORE: 7.2 - Medicine (Q1) - Biochemistry, Genetics and Molecular Biology (Q2)

Factor impacto SCIMAGO: 1.245 - Pathology and Forensic Medicine (Q1) - Molecular Medicine (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/E45-17R
Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP30-18
Financiación: info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/PIREPRED-EFA086/15
Financiación: info:eu-repo/grantAgreement/ES/MICINN/FPU16-04232
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PID2019- 107293GB-I00

Tipo y forma: Artículo (PostPrint)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)