Severus: accurate detection and characterization of somatic structural variation in tumor genomes using long reads

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 26, 2024

Abstract Most current studies rely on short-read sequencing to detect somatic structural variation (SV) in cancer genomes. Long-read offers the advantage of better mappability and long-range phasing, which results substantial improvements germline SV detection. However, long-read detection methods do not generalize well analysis SVs tumor genomes with complex rearrangements, heterogeneity, aneuploidy. Here, we present Severus: a method for accurate different types using phased breakpoint graph approach. To benchmark various short- methods, sequenced five tumor/normal cell line pairs Illumina, Nanopore, PacBio platforms; this Severus showed highest F1 scores (harmonic mean precision recall) as compared methods. We then applied three clinical cases pediatric cancer, demonstrating concordance known genetic findings revealing clinically relevant cryptic rearrangements missed by standard genomic panels.

Language: Английский

Impact and characterization of serial structural variations across humans and great apes

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 13, 2024

Abstract Modern sequencing technology enables the systematic detection of complex structural variation (SV) across genomes. However, extensive DNA rearrangements arising through a series mutations, phenomenon we refer to as serial SV (sSV), remain underexplored, posing challenge for discovery. Here, present NAHRwhals ( https://github.com/WHops/NAHRwhals ), method infer repeat-mediated SVs in long-read genomic assemblies. Applying haplotype-resolved human genomes from 28 individuals reveals 37 sSV loci various length and complexity. These sSVs explain otherwise cryptic medically relevant regions such TPSAB1 gene, 8p23.1, 22q11 Sotos syndrome regions. Comparisons with great ape assemblies indicate that most formed recently, after human-ape split, involved non-repeat-mediated processes addition non-allelic homologous recombination. reliably discovers characterizes at scale independent species, uncovering their abundance suggesting broader implications disease.

Language: Английский

Severus detects somatic structural variation and complex rearrangements in cancer genomes using long-read sequencing

Nature Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Language: Английский