Long read sequencing enhances pathogenic and novel variation discovery in patients with rare diseases.

ABSTRACT: With ongoing improvements in the detection of complex genomic and epigenomic variations, long-read sequencing (LRS) technologies could serve as a unified platform for clinical genetic testing, particularly in rare disease settings, where nearly half of patients remain undiagnosed using existing technologies. Here, we report a simplified funnel-down filtration strategy aimed at enhancing the identification of small and large deleterious variants as well as abnormal episignature disease profiles from whole-genome LRS data. This approach detected all pathogenic single nucleotide, structural, and methylation variants in a positive control set (N = 76) including an independent sample set with known methylation profiles (N = 57). When applied to patients who previously had negative short-read te

SUBMITTER: Sinha S 

PROVIDER: S-EPMC11909103 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature