Detection of copy-number variations from NGS data using read depth information: a diagnostic performance evaluation
Olivier Quenez
(1)
,
Kevin Cassinari
(1)
,
Sophie Coutant
(1)
,
Francois Lecoquierre
(1)
,
Kilan Le Guennec
(1)
,
Stéphane Rousseau
(1)
,
Anne-Claire Richard
(1)
,
Stéphanie Vasseur
(2)
,
Emilie Bouvignies
(2)
,
Jacqueline Bou
(2)
,
Gwendoline Lienard
(2)
,
Sandrine Manase
(2)
,
Steeve Fourneaux
(1)
,
Nathalie Drouot
(2)
,
Virginie Nguyen-Viet
(2)
,
Myriam Vezain
(1)
,
Pascal Chambon
(1)
,
Géraldine Joly-Helas
(1)
,
Nathalie Le Meur
(1)
,
Mathieu Castelain
(1)
,
Anne Boland
(3, 4)
,
Jean-François Deleuze
(3, 4)
,
Isabelle Tournier
(1)
,
Francoise Charbonnier
(1)
,
Edwige Kasper
(1)
,
Gaëlle Bougeard
(1)
,
Thierry Frebourg
(1)
,
Pascale Saugier-Veber
(1)
,
Stephanie Baert-Desurmont
(1)
,
Dominique Campion
(1, 5)
,
Anne Rovelet-Lecrux
(1)
,
Gael Nicolas
(1)
Olivier Quenez
- Fonction : Auteur
- PersonId : 178034
- IdHAL : olivier-quenez
- ORCID : 0000-0002-8273-8505
- IdRef : 253121655
Sophie Coutant
- Fonction : Auteur
- PersonId : 178352
- IdHAL : sophie-coutant
Stéphane Rousseau
- Fonction : Auteur
- PersonId : 178973
- IdHAL : laure-guilhaudis
- ORCID : 0000-0002-6212-9593
- IdRef : 230659403
Steeve Fourneaux
- Fonction : Auteur
- PersonId : 1056134
Myriam Vezain
- Fonction : Auteur
- PersonId : 178359
- IdHAL : myriam-vezain
- ORCID : 0000-0002-8333-1360
- IdRef : 150719892
Anne Boland
- Fonction : Auteur
- PersonId : 757786
- ORCID : 0000-0001-8789-5676
Jean-François Deleuze
- Fonction : Auteur
- PersonId : 1015006
Isabelle Tournier
- Fonction : Auteur
- PersonId : 179697
- IdHAL : isabelle-tournier
- ORCID : 0000-0002-5544-048X
- IdRef : 123443911
Edwige Kasper
- Fonction : Auteur
- PersonId : 1056137
Gaëlle Bougeard
- Fonction : Auteur
- PersonId : 179119
- IdHAL : gaelle-bougeard
- ORCID : 0000-0002-1475-0254
- IdRef : 077042131
Stephanie Baert-Desurmont
- Fonction : Auteur
- PersonId : 179721
- IdHAL : stephanie-baert-desurmont
- IdRef : 076622614
Dominique Campion
- Fonction : Auteur
- PersonId : 863253
Anne Rovelet-Lecrux
- Fonction : Auteur
- PersonId : 178525
- IdHAL : anne-rovelet-lecrux
- ORCID : 0000-0003-4454-3659
- IdRef : 127676732
Gael Nicolas
- Fonction : Auteur
- PersonId : 178691
- IdHAL : gael-nicolas1
- ORCID : 0000-0001-9391-7800
- IdRef : 165828412
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.