130809 20240319081000.0 doi 10.1016/j.jmoldx.2022.01.005 sideral 128773 ART-2022-128773 eng Galano-Frutos, J. Universidad de Zaragoza (orcid)0000-0002-1896-7805 PirePred: an accurate online consensus tool to interpret newborn screening–related genetic variants in structural context 2022 Access copy available to the general public Unrestricted 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 info:eu-repo/grantAgreement/ES/DGA/E45-17R info:eu-repo/grantAgreement/ES/DGA/LMP30-18 info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/PIREPRED-EFA086/15 info:eu-repo/grantAgreement/ES/MICINN/FPU16-04232 info:eu-repo/grantAgreement/ES/MINECO/PID2019- 107293GB-I00 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 4.1 2022 PATHOLOGY 21 / 76 = 0.276 2022 Q2 T1 1.245 2022 Pathology and Forensic Medicine 2022 Q1 Molecular Medicine 2022 Q2 7.2 2022 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion García-Cebollada, H. Universidad de Zaragoza (orcid)0000-0002-9590-7371 López, A. Rosell, M. de la Cruz, X. Fernández-Recio, J. Sancho, J. Universidad de Zaragoza (orcid)0000-0002-2879-9200 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 24, 4 (2022), 406-425 J. mol. diagnostics JOURNAL OF MOLECULAR DIAGNOSTICS 1525-1578 4229440 http://zaguan.unizar.es/record/130809/files/texto_completo.pdf Postprint 2850878 http://zaguan.unizar.es/record/130809/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:130809 articulos driver 2024-03-18-14:05:50 ARTICLE