Cell-type-specific patterns and consequences of somatic mutation in development and aging brain.

ABSTRACT: Elucidating the role of somatic mutations in cancer, healthy tissues, and aging depends on methods that can accurately characterize somatic mosaicism across different cell types, as well as assay their impact on cellular function. Current technologies to study cell-type-specific somatic mutations within tissues are low-throughput. We developed Duplex-Multiome, incorporating duplex consensus sequencing to accurately identify somatic single-nucleotide variants (sSNV) from the same nucleus simultaneously analyzed for single-nucleus ATAC-seq (snATAC-seq) and RNA-seq (snRNA-seq). By introducing strand-tagging into the construction of snATAC-seq libraries, duplex sequencing reduces sequencing error by >10,000-fold while eliminating artifactual mutational signatures. When applied to 98%/2% mixed

SUBMITTER: Kriz AJ 

PROVIDER: S-EPMC12154604 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature