Approach to Cohort-Wide Re-Analysis of Exome Data in 1000 Individuals with Neurodevelopmental Disorders.
exome sequencing
neurodevelopmental disorder
re-analysis
Journal
Genes
ISSN: 2073-4425
Titre abrégé: Genes (Basel)
Pays: Switzerland
ID NLM: 101551097
Informations de publication
Date de publication:
22 12 2022
22 12 2022
Historique:
received:
25
10
2022
revised:
02
12
2022
accepted:
19
12
2022
entrez:
21
1
2023
pubmed:
22
1
2023
medline:
25
1
2023
Statut:
epublish
Résumé
The re-analysis of nondiagnostic exome sequencing (ES) has the potential to increase diagnostic yields in individuals with rare diseases, but its implementation in the daily routines of laboratories is limited due to restricted capacities. Here, we describe a systematic approach to re-analyse the ES data of a cohort consisting of 1040 diagnostic and nondiagnostic samples. We applied a strict filter cascade to reveal the most promising single-nucleotide variants (SNVs) of the whole cohort, which led to an average of 0.77 variants per individual that had to be manually evaluated. This variant set revealed seven novel diagnoses (0.8% of all nondiagnostic cases) and two secondary findings. Thirteen additional variants were identified by a scientific approach prior to this re-analysis and were also present in this variant set. This resulted in a total increase in the diagnostic yield of 2.3%. The filter cascade was optimised during the course of the study and finally resulted in sensitivity of 85%. After applying the filter cascade, our re-analysis took 20 h and enabled a workflow that can be used repeatedly. This work is intended to provide a practical recommendation for other laboratories wishing to introduce a resource-efficient re-analysis strategy into their clinical routine.
Identifiants
pubmed: 36672771
pii: genes14010030
doi: 10.3390/genes14010030
pmc: PMC9858523
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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