CAPICE: a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations

Shuang Li; K Joeri van der Velde; Dick de Ridder; Aalt D J van Dijk; Dimitrios Soudis; Leslie R Zwerwer; Patrick Deelen; Dennis Hendriksen; Bart Charbon; Marielle E van Gijn; Kristin Abbott; Birgit Sikkema-Raddatz; Cleo C van Diemen; Wilhelmina S Kerstjens-Frederikse; Richard J Sinke; Morris A Swertz

doi:10.1186/s13073-020-00775-w

CAPICE: a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations

Shuang Li, K Joeri van der Velde, Dick de Ridder, Aalt D J van Dijk, Dimitrios Soudis, Leslie R Zwerwer, Patrick Deelen, Dennis Hendriksen, Bart Charbon, Marielle E van Gijn, Kristin Abbott, Birgit Sikkema-Raddatz, Cleo C van Diemen, Wilhelmina S Kerstjens-Frederikse, Richard J Sinke, Morris A Swertz

Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Exome sequencing is now mainstream in clinical practice. However, identification of pathogenic Mendelian variants remains time-consuming, in part, because the limited accuracy of current computational prediction methods requires manual classification by experts. Here we introduce CAPICE, a new machine-learning-based method for prioritizing pathogenic variants, including SNVs and short InDels. CAPICE outperforms the best general (CADD, GAVIN) and consequence-type-specific (REVEL, ClinPred) computational prediction methods, for both rare and ultra-rare variants. CAPICE is easily added to diagnostic pipelines as pre-computed score file or command-line software, or using online MOLGENIS web service with API. Download CAPICE for free and open-source (LGPLv3) at https://github.com/molgenis/capice..

Original language	English
Article number	75
Pages (from-to)	75
Number of pages	11
Journal	Genome medicine
Volume	12
Issue number	1
DOIs	https://doi.org/10.1186/s13073-020-00775-w https://doi.org/10.1186/s13073-020-00775-w
Publication status	Published - 24-Aug-2020

Keywords

Variant pathogenicity prediction
Machine learning
Exome sequencing
Molecular consequence
Allele frequency
Clinical genetics
Genome diagnostics
NONCODING VARIANTS
PREDICTION
IDENTIFICATION
ELEMENTS
SCORE

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Li, S., van der Velde, K. J., de Ridder, D., van Dijk, A. D. J., Soudis, D., Zwerwer, L. R., Deelen, P., Hendriksen, D., Charbon, B., van Gijn, M. E., Abbott, K., Sikkema-Raddatz, B., van Diemen, C. C., Kerstjens-Frederikse, W. S., Sinke, R. J., & Swertz, M. A. (2020). CAPICE: a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations. Genome medicine, 12(1), 75. [75]. https://doi.org/10.1186/s13073-020-00775-w, https://doi.org/10.1186/s13073-020-00775-w

Li, Shuang ; van der Velde, K Joeri ; de Ridder, Dick ; van Dijk, Aalt D J ; Soudis, Dimitrios ; Zwerwer, Leslie R ; Deelen, Patrick ; Hendriksen, Dennis ; Charbon, Bart ; van Gijn, Marielle E ; Abbott, Kristin ; Sikkema-Raddatz, Birgit ; van Diemen, Cleo C ; Kerstjens-Frederikse, Wilhelmina S ; Sinke, Richard J ; Swertz, Morris A. / CAPICE : a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations. In: Genome medicine. 2020 ; Vol. 12, No. 1. pp. 75.

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title = "CAPICE: a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations",

abstract = "Exome sequencing is now mainstream in clinical practice. However, identification of pathogenic Mendelian variants remains time-consuming, in part, because the limited accuracy of current computational prediction methods requires manual classification by experts. Here we introduce CAPICE, a new machine-learning-based method for prioritizing pathogenic variants, including SNVs and short InDels. CAPICE outperforms the best general (CADD, GAVIN) and consequence-type-specific (REVEL, ClinPred) computational prediction methods, for both rare and ultra-rare variants. CAPICE is easily added to diagnostic pipelines as pre-computed score file or command-line software, or using online MOLGENIS web service with API. Download CAPICE for free and open-source (LGPLv3) at https://github.com/molgenis/capice..",

keywords = "Variant pathogenicity prediction, Machine learning, Exome sequencing, Molecular consequence, Allele frequency, Clinical genetics, Genome diagnostics, NONCODING VARIANTS, PREDICTION, IDENTIFICATION, ELEMENTS, SCORE",

author = "Shuang Li and {van der Velde}, {K Joeri} and {de Ridder}, Dick and {van Dijk}, {Aalt D J} and Dimitrios Soudis and Zwerwer, {Leslie R} and Patrick Deelen and Dennis Hendriksen and Bart Charbon and {van Gijn}, {Marielle E} and Kristin Abbott and Birgit Sikkema-Raddatz and {van Diemen}, {Cleo C} and Kerstjens-Frederikse, {Wilhelmina S} and Sinke, {Richard J} and Swertz, {Morris A}",

year = "2020",

month = aug,

day = "24",

doi = "10.1186/s13073-020-00775-w",

language = "English",

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Li, S , van der Velde, KJ, de Ridder, D, van Dijk, ADJ, Soudis, D, Zwerwer, LR , Deelen, P, Hendriksen, D, Charbon, B, van Gijn, ME, Abbott, K, Sikkema-Raddatz, B , van Diemen, CC , Kerstjens-Frederikse, WS , Sinke, RJ & Swertz, MA 2020, 'CAPICE: a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations', Genome medicine, vol. 12, no. 1, 75, pp. 75. https://doi.org/10.1186/s13073-020-00775-w, https://doi.org/10.1186/s13073-020-00775-w

CAPICE : a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations. / Li, Shuang ; van der Velde, K Joeri; de Ridder, Dick; van Dijk, Aalt D J; Soudis, Dimitrios; Zwerwer, Leslie R ; Deelen, Patrick; Hendriksen, Dennis; Charbon, Bart; van Gijn, Marielle E; Abbott, Kristin; Sikkema-Raddatz, Birgit ; van Diemen, Cleo C ; Kerstjens-Frederikse, Wilhelmina S ; Sinke, Richard J ; Swertz, Morris A.

In: Genome medicine, Vol. 12, No. 1, 75, 24.08.2020, p. 75.

Research output: Contribution to journal › Article › Academic › peer-review

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T2 - a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations

AU - Li, Shuang

AU - van der Velde, K Joeri

AU - de Ridder, Dick

AU - van Dijk, Aalt D J

AU - Soudis, Dimitrios

AU - Zwerwer, Leslie R

AU - Deelen, Patrick

AU - Hendriksen, Dennis

AU - Charbon, Bart

AU - van Gijn, Marielle E

AU - Abbott, Kristin

AU - Sikkema-Raddatz, Birgit

AU - van Diemen, Cleo C

AU - Kerstjens-Frederikse, Wilhelmina S

AU - Sinke, Richard J

AU - Swertz, Morris A

PY - 2020/8/24

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N2 - Exome sequencing is now mainstream in clinical practice. However, identification of pathogenic Mendelian variants remains time-consuming, in part, because the limited accuracy of current computational prediction methods requires manual classification by experts. Here we introduce CAPICE, a new machine-learning-based method for prioritizing pathogenic variants, including SNVs and short InDels. CAPICE outperforms the best general (CADD, GAVIN) and consequence-type-specific (REVEL, ClinPred) computational prediction methods, for both rare and ultra-rare variants. CAPICE is easily added to diagnostic pipelines as pre-computed score file or command-line software, or using online MOLGENIS web service with API. Download CAPICE for free and open-source (LGPLv3) at https://github.com/molgenis/capice..

AB - Exome sequencing is now mainstream in clinical practice. However, identification of pathogenic Mendelian variants remains time-consuming, in part, because the limited accuracy of current computational prediction methods requires manual classification by experts. Here we introduce CAPICE, a new machine-learning-based method for prioritizing pathogenic variants, including SNVs and short InDels. CAPICE outperforms the best general (CADD, GAVIN) and consequence-type-specific (REVEL, ClinPred) computational prediction methods, for both rare and ultra-rare variants. CAPICE is easily added to diagnostic pipelines as pre-computed score file or command-line software, or using online MOLGENIS web service with API. Download CAPICE for free and open-source (LGPLv3) at https://github.com/molgenis/capice..

KW - Variant pathogenicity prediction

KW - Machine learning

KW - Exome sequencing

KW - Molecular consequence

KW - Allele frequency

KW - Clinical genetics

KW - Genome diagnostics

KW - NONCODING VARIANTS

KW - PREDICTION

KW - IDENTIFICATION

KW - ELEMENTS

KW - SCORE

U2 - 10.1186/s13073-020-00775-w

DO - 10.1186/s13073-020-00775-w

M3 - Article

C2 - 32831124

VL - 12

SP - 75

JO - Genome medicine

JF - Genome medicine

SN - 1756-994X

IS - 1

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