Detection of copy-number variations from NGS data using read depth information: a diagnostic performance evaluation
In: ISSN: 1018-4813, 2020
academicJournal
Zugriff:
International audience ; 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.
Titel: |
Detection of copy-number variations from NGS data using read depth information: a diagnostic performance evaluation
|
---|---|
Autor/in / Beteiligte Person: | Quenez, Olivier ; Cassinari, Kevin ; Coutant, Sophie ; Lecoquierre, Francois ; Le Guennec, Kilan ; Rousseau, Stéphane ; Richard, Anne-Claire ; Vasseur, Stéphanie ; Bouvignies, Emilie ; Bou, Jacqueline ; Lienard, Gwendoline ; Manase, Sandrine ; Fourneaux, Steeve ; Drouot, Nathalie ; Nguyen-Viet, Virginie ; Vezain, Myriam ; Chambon, Pascal ; Joly-Helas, Géraldine ; Le Meur, Nathalie ; Castelain, Mathieu ; Boland, Anne ; Deleuze, Jean-François ; Tournier, Isabelle ; Charbonnier, Francoise ; Kasper, Edwige ; Bougeard, Gaëlle ; Frebourg, Thierry ; Saugier-Veber, Pascale ; Baert-Desurmont, Stephanie ; Campion, Dominique ; Rovelet-Lecrux, Anne ; Nicolas, Gael ; Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND) ; Université de Rouen Normandie (UNIROUEN) ; Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Service de génétique Rouen ; Rouen, CHU ; Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN) ; Normandie Université (NU) ; Centre National de Génotypage (CNG) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA) ; Centre Hospitalier du Rouvray ; Normandie Université (NU)-Normandie Université (NU) |
Link: | |
Zeitschrift: | ISSN: 1018-4813, 2020 |
Veröffentlichung: | HAL CCSD ; Nature Publishing Group, 2020 |
Medientyp: | academicJournal |
DOI: | 10.1038/s41431-020-0672-2 |
Schlagwort: |
|
Sonstiges: |
|