Detection of copy-number variations from NGS data using read depth information: a diagnostic performance evaluation.


Journal

European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235

Informations de publication

Date de publication:
01 2021
Historique:
received: 22 11 2019
accepted: 09 06 2020
revised: 20 05 2020
pubmed: 28 6 2020
medline: 17 8 2021
entrez: 28 6 2020
Statut: ppublish

Résumé

The detection of copy-number variations (CNVs) from NGS data is underexploited as chip-based or targeted techniques are still commonly used. We assessed the performances of a workflow centered on CANOES, a bioinformatics tool based on read depth information. We applied our workflow to gene panel (GP) and whole-exome sequencing (WES) data, and compared CNV calls to quantitative multiplex PCR of short fluorescent fragments (QMSPF) or array comparative genomic hybridization (aCGH) results. From GP data of 3776 samples, we reached an overall positive predictive value (PPV) of 87.8%. This dataset included a complete comprehensive QMPSF comparison of four genes (60 exons) on which we obtained 100% sensitivity and specificity. From WES data, we first compared 137 samples with aCGH and filtered comparable events (exonic CNVs encompassing enough aCGH probes) and obtained an 87.25% sensitivity. The overall PPV was 86.4% following the targeted confirmation of candidate CNVs from 1056 additional WES. In addition, our CANOES-centered workflow on WES data allowed the detection of CNVs with a resolution of single exons, allowing the detection of CNVs that were missed by aCGH. Overall, switching to an NGS-only approach should be cost-effective as it allows a reduction in overall costs together with likely stable diagnostic yields. Our bioinformatics pipeline is available at: https://gitlab.bioinfo-diag.fr/nc4gpm/canoes-centered-workflow .

Identifiants

pubmed: 32591635
doi: 10.1038/s41431-020-0672-2
pii: 10.1038/s41431-020-0672-2
pmc: PMC7852510
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

99-109

Investigateurs

Emmanuelle Génin (E)
Dominique Campion (D)
Jean-François Dartigues (JF)
Jean-François Deleuze (JF)
Jean-Charles Lambert (JC)
Richard Redon (R)
Thomas Ludwig (T)
Benjamin Grenier-Boley (B)
Sébastien Letort (S)
Pierre Lindenbaum (P)
Vincent Meyer (V)
Olivier Quenez (O)
Christian Dina (C)
Céline Bellenguez (C)
Camille Charbonnier (C)
Joanna Giemza (J)
Stéphanie Chatel (S)
Claude Férec (C)
Hervé Le Marec (H)
Luc Letenneur (L)
Gaël Nicolas (G)
Karen Rouault (K)
Delphine Bacq (D)
Anne Boland (A)
Doris Lechner (D)

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Auteurs

Olivier Quenez (O)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Kevin Cassinari (K)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Sophie Coutant (S)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

François Lecoquierre (F)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Kilan Le Guennec (K)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Stéphane Rousseau (S)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Anne-Claire Richard (AC)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Stéphanie Vasseur (S)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Emilie Bouvignies (E)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Jacqueline Bou (J)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Gwendoline Lienard (G)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Sandrine Manase (S)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Steeve Fourneaux (S)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Nathalie Drouot (N)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Virginie Nguyen-Viet (V)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Myriam Vezain (M)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Pascal Chambon (P)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Géraldine Joly-Helas (G)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Nathalie Le Meur (N)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Mathieu Castelain (M)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Anne Boland (A)

Centre National de Recherche en Génomique Humaine, Institut de Génomique, CEA and Fondation Jean Dausset-CEPH, Evry, France.

Jean-François Deleuze (JF)

Centre National de Recherche en Génomique Humaine, Institut de Génomique, CEA and Fondation Jean Dausset-CEPH, Evry, France.

Isabelle Tournier (I)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Françoise Charbonnier (F)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Edwige Kasper (E)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Gaëlle Bougeard (G)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Thierry Frebourg (T)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Pascale Saugier-Veber (P)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Stéphanie Baert-Desurmont (S)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Dominique Campion (D)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France.
Department of research, Centre hospitalier du Rouvray, Sotteville-lès-Rouen, France.

Anne Rovelet-Lecrux (A)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France.

Gaël Nicolas (G)

Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France. gaelnicolas@hotmail.com.

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