GAVIN: Gene-Aware Variant INterpretation for medical sequencing

We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele frequencies from the ExAC database, likely variant impact using SnpEff, and estimated deleterious...

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Autores principales: van der Velde, K. Joeri, de Boer, Eddy N., van Diemen, Cleo C., Sikkema-Raddatz, Birgit, Abbott, Kristin M., Knopperts, Alain, Franke, Lude, Sijmons, Rolf H., de Koning, Tom J., Wijmenga, Cisca, Sinke, Richard J., Swertz, Morris A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Method
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240400/
https://www.ncbi.nlm.nih.gov/pubmed/28093075
http://dx.doi.org/10.1186/s13059-016-1141-7
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author van der Velde, K. Joeri
de Boer, Eddy N.
van Diemen, Cleo C.
Sikkema-Raddatz, Birgit
Abbott, Kristin M.
Knopperts, Alain
Franke, Lude
Sijmons, Rolf H.
de Koning, Tom J.
Wijmenga, Cisca
Sinke, Richard J.
Swertz, Morris A.
author_facet van der Velde, K. Joeri
de Boer, Eddy N.
van Diemen, Cleo C.
Sikkema-Raddatz, Birgit
Abbott, Kristin M.
Knopperts, Alain
Franke, Lude
Sijmons, Rolf H.
de Koning, Tom J.
Wijmenga, Cisca
Sinke, Richard J.
Swertz, Morris A.
author_sort van der Velde, K. Joeri
collection PubMed
description We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele frequencies from the ExAC database, likely variant impact using SnpEff, and estimated deleteriousness based on CADD scores for >3000 genes. In a benchmark on 18 clinical gene sets, we achieve a sensitivity of 91.4% and a specificity of 76.9%. This accuracy is unmatched by 12 other tools. We provide GAVIN as an online MOLGENIS service to annotate VCF files and as an open source executable for use in bioinformatic pipelines. It can be found at http://molgenis.org/gavin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1141-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-52404002017-01-23 GAVIN: Gene-Aware Variant INterpretation for medical sequencing van der Velde, K. Joeri de Boer, Eddy N. van Diemen, Cleo C. Sikkema-Raddatz, Birgit Abbott, Kristin M. Knopperts, Alain Franke, Lude Sijmons, Rolf H. de Koning, Tom J. Wijmenga, Cisca Sinke, Richard J. Swertz, Morris A. Genome Biol Method We present Gene-Aware Variant INterpretation (GAVIN), a new method that accurately classifies variants for clinical diagnostic purposes. Classifications are based on gene-specific calibrations of allele frequencies from the ExAC database, likely variant impact using SnpEff, and estimated deleteriousness based on CADD scores for >3000 genes. In a benchmark on 18 clinical gene sets, we achieve a sensitivity of 91.4% and a specificity of 76.9%. This accuracy is unmatched by 12 other tools. We provide GAVIN as an online MOLGENIS service to annotate VCF files and as an open source executable for use in bioinformatic pipelines. It can be found at http://molgenis.org/gavin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1141-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-01-16 /pmc/articles/PMC5240400/ /pubmed/28093075 http://dx.doi.org/10.1186/s13059-016-1141-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Method
van der Velde, K. Joeri
de Boer, Eddy N.
van Diemen, Cleo C.
Sikkema-Raddatz, Birgit
Abbott, Kristin M.
Knopperts, Alain
Franke, Lude
Sijmons, Rolf H.
de Koning, Tom J.
Wijmenga, Cisca
Sinke, Richard J.
Swertz, Morris A.
GAVIN: Gene-Aware Variant INterpretation for medical sequencing
title GAVIN: Gene-Aware Variant INterpretation for medical sequencing
title_full GAVIN: Gene-Aware Variant INterpretation for medical sequencing
title_fullStr GAVIN: Gene-Aware Variant INterpretation for medical sequencing
title_full_unstemmed GAVIN: Gene-Aware Variant INterpretation for medical sequencing
title_short GAVIN: Gene-Aware Variant INterpretation for medical sequencing
title_sort gavin: gene-aware variant interpretation for medical sequencing
topic Method
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240400/
https://www.ncbi.nlm.nih.gov/pubmed/28093075
http://dx.doi.org/10.1186/s13059-016-1141-7
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