Single-nuclei transcriptomics enable detection of somatic variants in patient brain tissue.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 01 2023
11 01 2023
Historique:
received:
01
08
2022
accepted:
06
01
2023
entrez:
11
1
2023
pubmed:
12
1
2023
medline:
14
1
2023
Statut:
epublish
Résumé
Somatic variants are a major cause of human disease, including neurological disorders like focal epilepsies, but can be challenging to study due to their mosaicism in bulk tissue biopsies. Coupling single-cell genotype and transcriptomic data has potential to provide insight into the role somatic variants play in disease etiology, such as by determining what cell types are affected or how the mutations affect gene expression. Here, we asked whether commonly used single-nucleus 3'- or 5'-RNA-sequencing assays can be used to derive single-nucleus genotype data for a priori known variants that are located near to either end of a transcript. To that end, we compared performance of commercially available single-nuclei 3'- and 5'- gene expression kits using resected brain samples from three pediatric patients with focal epilepsy. We quantified the ability to detect genetic variants in single-nucleus datasets depending on distance from the transcript end. Finally, we demonstrated the ability to identify affected cell types in a patient with a RHEB somatic variant causing an epilepsy-associated cortical malformation. Our results demonstrate that single-nuclei 3' or 5'-RNA-sequencing data can be used to identify known somatic variants in single-nuclei when they are expressed within proximity to a transcript end.
Identifiants
pubmed: 36631516
doi: 10.1038/s41598-023-27700-6
pii: 10.1038/s41598-023-27700-6
pmc: PMC9834227
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
527Informations de copyright
© 2023. The Author(s).
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