Now Reading: Severus detects somatic structural variation and complex rearrangements in cancer genomes using long-read sequencing
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Severus detects somatic structural variation and complex rearrangements in cancer genomes using long-read sequencing
Severus detects somatic structural variation and complex rearrangements in cancer genomes using long-read sequencing
Data availability
The sequencing data for the CASTLE panel produced in this study are openly available at NCBI SRA BioProject PRJNA1086849. Sequencing of the clinical samples is under controlled access and is available through dbGaP study phs002529. Individual accession codes of SRA and dbGaP datasets are provided in Supplementary Table 2 and at https://github.com/CASTLE-Panel/castle. The outputs of all tools, evaluations and command line scripts are available at Zenodo at https://doi.org/10.5281/zenodo.10856827 (ref. 74). The hg38 reference genome is available via NCBI (GCF_000001405.26). The 1000 Genomes Vienna SV panel is available at https://ftp.1000genomes.ebi.ac.uk/vol1/ftp/data_collections/1KG_ONT_VIENNA/release/v1.0/delly-unfiltered-hg38/. Accession codes and references for publicly available datasets (COLO829, HCC1395, HG002, CHM1 and CHM13) are available in Supplementary Table 2.
Code availability
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Acknowledgements
The work was supported, in part, by the Intramural Research Program of the National Institutes of Health (NIH). This work used the computational resources of the NIH High-Performance Computing Biowulf cluster (http://hpc.nih.gov). ONT sequencing of the HCC1395 cell line was supported by the National Cancer Institute of the NIH under award number U01CA253405. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We would like to thank the participants and families who donated their samples for this research. M.S.F. and E.G. would like to thank Braden’s Hope for Childhood Cancer, Elizabeth and Monte McDowell, the Black & Veatch Foundation, Curing Kids Cancer and Big Slick for their generous support. M.S.F., E.G. and L.A.L. would also like to thank Children’s Mercy Oncology Biorepository study personnel, including J. Vun, A. Hatfield and R. Ryan, as well as J. Seymour and K. Sanders in the Children’s Mercy Research Institute Biorepository for their assistance with sample collection and processing and M. Gibson, A. Walter and L. Puckett in the Children’s Mercy Research Institute Genomics Core for their assistance with sequencing. Y.L. is funded by the NCI-UMD Partnership Program. E.K.M. was supported by the State of Maryland. B.P. was supported by the NHGRI under award numbers R01HG010485, U01HG013748, U24HG011853, U24HG010262 and U41HG010972 and NIH award OT2OD033761. K.H.M. was supported by NIH/NHGRI R01HG011274. We thank A. Liss for creating the broadly consented pancreatic cancer cell line HG008-T. We thank J. McDaniel, V. Patel, N. Olson, J. Wagner and J. Zook at NIST and C. Xiao at NCBI for providing guidance and documentation for using the HG008 data and the GIAB Consortium for releasing all data publicly without embargo. The chromosome illustrations in Figs. 5 and 6 and Extended Data Figs. 7 and 8 were created using BioRender (https://BioRender.com/z86y662). We acknowledge the Gurobi team for providing an academic license free of charge.
Ethics declarations
Competing interests
S.A. is an employee and stockholder of ONT. A.K., P.C., K.S., D.C. and A.C. are employees of Google and own Alphabet stock as part of the standard compensation package. E.G. served on advisory boards for Jazz Pharmaceuticals and Syndax Pharmaceuticals. M.S.F. is part of the speakers bureau for Bayer and PacBio. The other authors declare no competing interests.
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Nature Biotechnology thanks Q. Chris Liu, Kai Ye and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Keskus, A.G., Bryant, A., Ahmad, T. et al. Severus detects somatic structural variation and complex rearrangements in cancer genomes using long-read sequencing.
Nat Biotechnol (2025). https://doi.org/10.1038/s41587-025-02618-8
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DOI: https://doi.org/10.1038/s41587-025-02618-8
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