Performance of somatic structural variant calling in lung cancer using Oxford Nanopore sequencing technology.

Autor: Liu L; QIMR Berghofer Medical Research Institute, Brisbane, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, Australia., Zhang J; QIMR Berghofer Medical Research Institute, Brisbane, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, Australia., Wood S; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Newell F; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Leonard C; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Koufariotis LT; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Nones K; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Dalley AJ; Faculty of Medicine, The University of Queensland, Brisbane, Australia., Chittoory H; Faculty of Medicine, The University of Queensland, Brisbane, Australia., Bashirzadeh F; Department of Thoracic Medicine, The Royal Brisbane & Women's Hospital, Brisbane, Australia., Son JH; Department of Thoracic Medicine, The Royal Brisbane & Women's Hospital, Brisbane, Australia., Steinfort D; Department of Thoracic Medicine, Royal Melbourne Hospital, Melbourne, Australia., Williamson JP; Department of Thoracic Medicine, Liverpool Hospital Sydney, Sydney, Australia., Bint M; Department of Thoracic Medicine, Sunshine Coast University Hospital, Birtinya, Australia., Pahoff C; Department of Thoracic Medicine, Gold Coast University Hospital, Southport, Australia., Nguyen PT; Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia., Twaddell S; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, Australia., Arnold D; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, Australia., Grainge C; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, Australia., Simpson PT; Faculty of Medicine, The University of Queensland, Brisbane, Australia., Fielding D; Faculty of Medicine, The University of Queensland, Brisbane, Australia.; Department of Thoracic Medicine, The Royal Brisbane & Women's Hospital, Brisbane, Australia., Waddell N; QIMR Berghofer Medical Research Institute, Brisbane, Australia. nic.waddell@qimrberghofer.edu.au.; Faculty of Medicine, The University of Queensland, Brisbane, Australia. nic.waddell@qimrberghofer.edu.au., Pearson JV; QIMR Berghofer Medical Research Institute, Brisbane, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2024 Sep 30; Vol. 25 (1), pp. 898. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1186/s12864-024-10792-3
Abstrakt: Background: Lung cancer is a heterogeneous disease and the primary cause of cancer-related mortality worldwide. Somatic mutations, including large structural variants, are important biomarkers in lung cancer for selecting targeted therapy. Genomic studies in lung cancer have been conducted using short-read sequencing. Emerging long-read sequencing technologies are a promising alternative to study somatic structural variants, however there is no current consensus on how to process data and call somatic events. In this study, we preformed whole genome sequencing of lung cancer and matched non-tumour samples using long and short read sequencing to comprehensively benchmark three sequence aligners and seven structural variant callers comprised of generic callers (SVIM, Sniffles2, DELLY in generic mode and cuteSV) and somatic callers (Severus, SAVANA, nanomonsv and DELLY in somatic modes).
Results: Different combinations of aligners and variant callers influenced somatic structural variant detection. The choice of caller had a significant influence on somatic structural variant detection in terms of variant type, size, sensitivity, and accuracy. The performance of each variant caller was assessed by comparing to somatic structural variants identified by short-read sequencing. When compared to somatic structural variants detected with short-read sequencing, more events were detected with long-read sequencing. The mean recall of somatic variant events identified by long-read sequencing was higher for the somatic callers (72%) than generic callers (53%). Among the somatic callers when using the minimap2 aligner, SAVANA and Severus achieved the highest recall at 79.5% and 79.25% respectively, followed by nanomonsv with a recall of 72.5%.
Conclusion: Long-read sequencing can identify somatic structural variants in clincal samples. The longer reads have the potential to improve our understanding of cancer development and inform personalized cancer treatment.
(© 2024. The Author(s).)
Databáze: MEDLINE
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