Benchmarking long-read structural variant calling tools and combinations for detecting somatic variants in cancer genomes.

Date

2025-03-13

Author

Aydin, Safa Kerem
Yilmaz, Kubra Celikbas
Acar, Ahmet

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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Cancer genomes have a complicated landscape of mutations, including large-scale rearrangements known as structural variants (SVs). These SVs can disrupt genes or regulatory elements, playing a critical role in cancer development and progression. Despite their importance, accurate identification of somatic structural variants (SVs) remains a significant bottleneck in cancer genomics. Long-read sequencing technologies hold great promise in SV discovery, and there is an increasing number of efforts to develop new tools to detect them. In this study, we employ eight widely used SV callers on paired tumor and matched normal samples from both the NCI-H2009 lung cancer cell line and the COLO829 melanoma cell line, the latter of which has a well-established somatic SV truth set. Following separate variation detection in both tumor and normal DNA, the VCF merging procedure and a subtraction method were used to identify candidate somatic SVs. Additionally, we explored different combinations of the tools to enhance the accuracy of true somatic SV detection. Our analysis adopts a comprehensive approach, evaluating the performance of each SV caller across a spectrum of variant types and numbers in finding cancer-related somatic SVs. This study, by comparing eight different tools and their combinations, not only reveals the benefits and limitations of various techniques but also establishes a framework for developing more robust SV calling pipelines. Our findings highlight the strengths and weaknesses of current SV calling tools and suggest that combining multiple tools and testing different combinations can significantly enhance the validation of somatic alterations.

Subject Keywords

Tool benchmarking, Cancer genomics, Long-read sequencing, Somatic structural variants, SV calling tools, Whole-genome sequencing data

URI

https://hdl.handle.net/11511/114386

Collections

Department of Biology, Article