Scholarlink

<p>For the detection of somatic structural variation (SV) in cancer genomes, long-read sequencing is advantageous over short-read sequencing with respect to mappability and variant phasing. However, most current long-read SV detection methods are not developed for the analysis of tumor genomes characterized by complex rearrangements and heterogeneity. Here, we present Severus, a breakpoint graph-based algorithm for somatic SV calling from long-read cancer sequencing. Severus works with matching normal samples, supports unbalanced cancer karyotypes, can characterize complex multibreak SV patterns and produces haplotype-specific calls. On a comprehensive multitechnology cell line panel, Severus consistently outperforms other long-read and short-read methods in terms of SV detection F1 score (harmonic mean of the precision and recall). We also illustrate that compared to long-read methods, short-read sequencing systematically misses certain classes of somatic SVs, such as insertions or clustered rearrangements. We apply Severus to several clinical cases of pediatric leukemia/lymphoma, revealing clinically relevant cryptic rearrangements missed by standard genomic panels.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2025年4月4日

查看全文
  • Ayse G. Keskus,
  • Asher Bryant,
  • Tanveer Ahmad,
  • Byunggil Yoo,
  • Sergey Aganezov,
  • Anton Goretsky,
  • Ataberk Donmez,
  • Lisa A. Lansdon,
  • Isabel Rodriguez,
  • Jimin Park,
  • Yuelin Liu,
  • Xiwen Cui,
  • Joshua Gardner,
  • Brandy McNulty,
  • Samuel Sacco,
  • Jyoti Shetty,
  • Yongmei Zhao,
  • Bao Tran,
  • Giuseppe Narzisi,
  • Adrienne Helland,
  • Daniel E. Cook,
  • Pi-Chuan Chang,
  • Alexey Kolesnikov,
  • Andrew Carroll,
  • Erin K. Molloy,
  • Chengpeng Bi,
  • Adam Walter,
  • Margaret Gibson,
  • Irina Pushel,
  • Erin Guest,
  • Tomi Pastinen,
  • Kishwar Shafin,
  • Karen H. Miga,
  • Salem Malikic,
  • Chi-Ping Day,
  • Nicolas Robine,
  • Cenk Sahinalp,
  • Michael Dean,
  • Midhat S. Farooqi,
  • Benedict Paten,
  • Mikhail Kolmogorov

摘要

For the detection of somatic structural variation (SV) in cancer genomes, long-read sequencing is advantageous over short-read sequencing with respect to mappability and variant phasing. However, most current long-read SV detection methods are not developed for the analysis of tumor genomes characterized by complex rearrangements and heterogeneity. Here, we present Severus, a breakpoint graph-based algorithm for somatic SV calling from long-read cancer sequencing. Severus works with matching normal samples, supports unbalanced cancer karyotypes, can characterize complex multibreak SV patterns and produces haplotype-specific calls. On a comprehensive multitechnology cell line panel, Severus consistently outperforms other long-read and short-read methods in terms of SV detection F1 score (harmonic mean of the precision and recall). We also illustrate that compared to long-read methods, short-read sequencing systematically misses certain classes of somatic SVs, such as insertions or clustered rearrangements. We apply Severus to several clinical cases of pediatric leukemia/lymphoma, revealing clinically relevant cryptic rearrangements missed by standard genomic panels.