PirePred: An Accurate Online Consensus Tool to Interpret Newborn Screening–Related Genetic Variants in Structural Context
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.
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2022-03-29
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dig-icvv-es-10261-2764982022-11-25T13:05:50Z PirePred: An Accurate Online Consensus Tool to Interpret Newborn Screening–Related Genetic Variants in Structural Context Galano-Frutos, Juan J. García-Cebollada, Helena López, Alfonso Rosell, Mireia Cruz, Xavier de la Fernández-Recio, Juan Sancho, Javier Interreg POCTEFA Ministerio de Economía y Competitividad (España) Gobierno de Aragón 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. Supported by 2014–2020 Interreg V-A Spain-France-Andorra (POCTEFA) grant EFA086/15, Mineco grant PID2019-107293GB-I00, and Gobierno de Aragón grants E45_17R and LMP30_18. H.G.-C. is the recipient of an FPU16/04232 doctoral contract from MCIN. 2022-08-23T10:30:03Z 2022-08-23T10:30:03Z 2022-03-29 2022-08-23T10:30:03Z artículo doi: 10.1016/j.jmoldx.2022.01.005 issn: 1943-7811 Journal of Molecular Diagnostics 24: 406-425 (2022) 1525-1578 http://hdl.handle.net/10261/276498 10.1016/j.jmoldx.2022.01.005 http://dx.doi.org/10.13039/501100010067 http://dx.doi.org/10.13039/100013276 http://dx.doi.org/10.13039/501100003329 #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107293GB-I00/ES/COMPRENSION CUANTITATIVA DE ESTABILIDAD DE PROTEINAS POR MODELADO Y SIMULACION, Y APLICACION A LA INTERPRETACION CINETICA Y TERMODINAMICA DE VARIANTES EN UN SOLO AMINOACIDO/ info:eu-repo/grantAgreement/MECD//FPU16%2F04232/ES/FPU16%2F04232/ Postprint http://dx.doi.org/10.1016/j.jmoldx.2022.01.005 Sí none Elsevier |
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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. |
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Interreg POCTEFA |
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Interreg POCTEFA Galano-Frutos, Juan J. García-Cebollada, Helena López, Alfonso Rosell, Mireia Cruz, Xavier de la Fernández-Recio, Juan Sancho, Javier |
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Galano-Frutos, Juan J. García-Cebollada, Helena López, Alfonso Rosell, Mireia Cruz, Xavier de la Fernández-Recio, Juan Sancho, Javier |
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Galano-Frutos, Juan J. García-Cebollada, Helena López, Alfonso Rosell, Mireia Cruz, Xavier de la Fernández-Recio, Juan Sancho, Javier PirePred: An Accurate Online Consensus Tool to Interpret Newborn Screening–Related Genetic Variants in Structural Context |
author_sort |
Galano-Frutos, Juan J. |
title |
PirePred: An Accurate Online Consensus Tool to Interpret Newborn Screening–Related Genetic Variants in Structural Context |
title_short |
PirePred: An Accurate Online Consensus Tool to Interpret Newborn Screening–Related Genetic Variants in Structural Context |
title_full |
PirePred: An Accurate Online Consensus Tool to Interpret Newborn Screening–Related Genetic Variants in Structural Context |
title_fullStr |
PirePred: An Accurate Online Consensus Tool to Interpret Newborn Screening–Related Genetic Variants in Structural Context |
title_full_unstemmed |
PirePred: An Accurate Online Consensus Tool to Interpret Newborn Screening–Related Genetic Variants in Structural Context |
title_sort |
pirepred: an accurate online consensus tool to interpret newborn screening–related genetic variants in structural context |
publisher |
Elsevier |
publishDate |
2022-03-29 |
url |
http://hdl.handle.net/10261/276498 http://dx.doi.org/10.13039/501100010067 http://dx.doi.org/10.13039/100013276 http://dx.doi.org/10.13039/501100003329 |
work_keys_str_mv |
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