GAVIN: Gene-Aware Variant INterpretation for medical sequencing

K Joeri van der Velde; Eddy N de Boer; Cleo C van Diemen; Birgit Sikkema-Raddatz; Kristin M Abbott; Alain Knopperts; Lude Franke; Rolf H Sijmons; Tom J de Koning; Cisca Wijmenga; Richard J Sinke; Morris A Swertz

doi:10.1186/s13059-016-1141-7

GAVIN: Gene-Aware Variant INterpretation for medical sequencing

K Joeri van der Velde, Eddy N de Boer, Cleo C van Diemen, Birgit Sikkema-Raddatz, Kristin M Abbott, Alain Knopperts, Lude Franke, Rolf H Sijmons, Tom J de Koning, Cisca Wijmenga, Richard J Sinke, Morris A Swertz

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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 .

Originele taal-2	English
Artikelnummer	6
Aantal pagina's	10
Tijdschrift	Genome Biology
Volume	18
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1186/s13059-016-1141-7
Status	Published - 16-jan.-2017

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10.1186/s13059-016-1141-7Licentie: CC BY

GAVIN Gene-Aware Variant INterpretation for medical sequencingFinal publisher's version, 1,08 MBLicentie: CC BY

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Additional file 4: Table S4. of GAVIN: Gene-Aware Variant INterpretation for medical sequencing
van Diemen, C. (Contributor), Wijmenga, C. (Contributor), Franke, L. (Contributor), van der Velde, J. (Contributor), Sinke, R. (Contributor), Swertz, M. (Contributor), Raddatz, B. (Contributor), de Boer, E. (Contributor), Knopperts, A. (Contributor), de Koning, T. J. (Contributor), Sijmons, R. (Contributor) & Abbott, K. (Contributor), University of Groningen, 16-jan.-2017
DOI: 10.6084/m9.figshare.c.3666643_d1.v1
Dataset
Additional file 2: Table S2. of GAVIN: Gene-Aware Variant INterpretation for medical sequencing
de Koning, T. J. (Contributor), Sijmons, R. (Contributor), Raddatz, B. (Contributor), Swertz, M. (Contributor), de Boer, E. (Contributor), Wijmenga, C. (Contributor), Sinke, R. (Contributor), van Diemen, C. (Contributor), Knopperts, A. (Contributor), Franke, L. (Contributor), Abbott, K. (Contributor) & van der Velde, J. (Contributor), University of Groningen, 16-jan.-2017
DOI: 10.6084/m9.figshare.c.3666643_d2.v1
Dataset
Additional file 1: Table S1. of GAVIN: Gene-Aware Variant INterpretation for medical sequencing
van der Velde, J. (Contributor), de Boer, E. (Contributor), van Diemen, C. (Contributor), Raddatz, B. (Creator), Abbott, K. (Creator), Knopperts, A. (Creator), Franke, L. (Creator), Sijmons, R. (Creator), de Koning, T. J. (Contributor), Wijmenga, C. (Creator), Sinke, R. (Creator) & Swertz, M. (Creator), figshare, 16-jan.-2017
DOI: 10.6084/m9.figshare.c.3666643_d4
Dataset

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title = "GAVIN: Gene-Aware Variant INterpretation for medical sequencing",

abstract = "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 .",

keywords = "Clinical next-generation sequencing, Variant classification, Automated protocol, Gene-specific calibration, Allele frequency, Protein impact, Pathogenicity prediction, NONCODING VARIANTS, PATHOGENICITY, MUTATIONS, DATABASE, DISEASE, GENOME, MODEL, SCORE",

author = "{van der Velde}, {K Joeri} and {de Boer}, {Eddy N} and {van Diemen}, {Cleo C} and Birgit Sikkema-Raddatz and Abbott, {Kristin M} and Alain Knopperts and Lude Franke and Sijmons, {Rolf H} and {de Koning}, {Tom J} and Cisca Wijmenga and Sinke, {Richard J} and Swertz, {Morris A}",

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AU - van der Velde, K Joeri

AU - de Boer, Eddy N

AU - van Diemen, Cleo C

AU - Sikkema-Raddatz, Birgit

AU - Abbott, Kristin M

AU - Knopperts, Alain

AU - Franke, Lude

AU - Sijmons, Rolf H

AU - de Koning, Tom J

AU - Wijmenga, Cisca

AU - Sinke, Richard J

AU - Swertz, Morris A

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N2 - 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 .

AB - 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 .

KW - Clinical next-generation sequencing

KW - Variant classification

KW - Automated protocol

KW - Gene-specific calibration

KW - Allele frequency

KW - Protein impact

KW - Pathogenicity prediction

KW - NONCODING VARIANTS

KW - PATHOGENICITY

KW - MUTATIONS

KW - DATABASE

KW - DISEASE

KW - GENOME

KW - MODEL

KW - SCORE

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DO - 10.1186/s13059-016-1141-7

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VL - 18

JO - Genome Biology

JF - Genome Biology

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M1 - 6

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GAVIN: Gene-Aware Variant INterpretation for medical sequencing

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Additional file 4: Table S4. of GAVIN: Gene-Aware Variant INterpretation for medical sequencing

Additional file 2: Table S2. of GAVIN: Gene-Aware Variant INterpretation for medical sequencing

Additional file 1: Table S1. of GAVIN: Gene-Aware Variant INterpretation for medical sequencing

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