Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples.

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:
19 Oct 2023

Historique:

received: 01 11 2022

accepted: 04 10 2023

revised: 29 08 2023

pubmed: 19 10 2023

medline: 19 10 2023

entrez: 18 10 2023

Statut: aheadofprint

Résumé

Mobile element insertions (MEIs) are a known cause of genetic disease but have been underexplored due to technical limitations of genetic testing methods. Various bioinformatic tools have been developed to identify MEIs in Next Generation Sequencing data. However, most tools have been developed specifically for genome sequencing (GS) data rather than exome sequencing (ES) data, which remains more widely used for routine diagnostic testing. In this study, we benchmarked six MEI detection tools (ERVcaller, MELT, Mobster, SCRAMble, TEMP2 and xTea) on ES data and on GS data from publicly available genomic samples (HG002, NA12878). For all the tools we evaluated sensitivity and precision of different filtering strategies. Results show that there were substantial differences in tool performance between ES and GS data. MELT performed best with ES data and its combination with SCRAMble increased substantially the detection rate of MEIs. By applying both tools to 10,890 ES samples from Solve-RD and 52,624 samples from Radboudumc we were able to diagnose 10 patients who had remained undiagnosed by conventional ES analysis until now. Our study shows that MELT and SCRAMble can be used reliably to identify clinically relevant MEIs in ES data. This may lead to an additional diagnosis for 1 in 3000 to 4000 patients in routine clinical ES.

Identifiants

DOI: 10.1038/s41431-023-01478-7 PMID: 37853102

pubmed: 37853102

doi: 10.1038/s41431-023-01478-7

pii: 10.1038/s41431-023-01478-7

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Commentaires et corrections

Type : ErratumIn

Informations de copyright

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