Evaluating the Transition from Targeted to Exome Sequencing: A Guide for Clinical Laboratories

Author:

Yauy Kevin12,Van Goethem Charles1ORCID,Pégeot Henri1,Baux David13ORCID,Guignard Thomas4,Thèze Corinne1,Ardouin Olivier5,Roux Anne-Françoise13ORCID,Koenig Michel16,Bergougnoux Anne16,Cossée Mireille16ORCID

Affiliation:

1. Laboratoire de Génétique Moléculaire, LGM, Centre Hospitalier Universitaire de Montpellier, IURC—Institut Universitaire de Recherche Clinique, 641 Avenue du Doyen G. Giraud, 34090 Montpellier, France

2. Service de Génétique Médicale, CHU Montpellier, 371 Avenue du Doyen G. Giraud, 34090 Montpellier, France

3. INM, Université de Montpellier, INSERM, Hôpital Saint Eloi-Bâtiment INM 80, rue Augustin Fliche-BP 74103, 34090 Montpellier, France

4. Unité de Génétique Chromosomique, Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Hôpital Arnaud de Villeneuve, CHU de Montpellier, 371 Av. du Doyen Gaston Giraud, 34090 Montpellier, France

5. Plateau de Médecine Moléculaire et Génomique, Hôpital Arnaud de Villeneuve, CHU de Montpellier, 34090 Montpellier, France

6. PhyMedExp-Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Inserm U1046, CNRS UMR 9214, 371 Avenue du Doyen G. Giraud, 34090 Montpellier, France

Abstract

The transition from targeted to exome or genome sequencing in clinical contexts requires quality standards, such as targeted sequencing, in order to be fully adopted. However, no clear recommendations or methodology have emerged for evaluating this technological evolution. We developed a structured method based on four run-specific sequencing metrics and seven sample-specific sequencing metrics for evaluating the performance of exome sequencing strategies to replace targeted strategies. The indicators include quality metrics and coverage performance on gene panels and OMIM morbid genes. We applied this general strategy to three different exome kits and compared them with a myopathy-targeted sequencing method. After having achieved 80 million reads, all-tested exome kits generated data suitable for clinical diagnosis. However, significant differences in the coverage and PCR duplicates were observed between the kits. These are two main criteria to consider for the initial implementation with high-quality assurance. This study aims to assist molecular diagnostic laboratories in adopting and evaluating exome sequencing kits in a diagnostic context compared to the strategy used previously. A similar strategy could be used to implement whole-genome sequencing for diagnostic purposes.

Funder

AFM

Agence de la Biomédecine

CHU Montpellier

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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