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


Keskus et al. developed Severus, a breakpoint graph-based algorithm for somatic structural variant (SV) calling from Oxford Nanopore and PacBio data. Severus outperformed other long- and short-read SV callers and identified clinically relevant rearrangements in tumour samples that were missed by standard genomic panels. This research demonstrates the value of accurate SV calling for precision oncology and provides new tools and data to advance cancer genomics in the future.

Key points:

  • Severus works with tumour-only and matched normal samples, produces haplotype-specific SV calling, characterises complex SV patterns, and supports unbalanced cancer karyotypes

  • Severus identified clinically relevant, cryptic SVs in paediatric leukaemia and lymphoma research samples that were missed by routine clinical tests

  • Using a phased breakpoint graph, Severus reconstructed complex genomic events such as chromoplexy

  • This algorithm outperforms existing SV detection methods, which struggle with the complex rearrangements and heterogeneity associated with tumour SV calling

Watch the talk by Mikhail Kolmogorov and Ayse Keskus at AACR 2024

Sample type: tumour-normal cell lines, blood cancer clinical research samples

Kit: Ligation Sequencing Kit

Authors: 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