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Comparative analysis of methodologies for detecting extrachromosomal circular DNA

Author

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  • Xuyuan Gao

    (University of Science and Technology of China)

  • Ke Liu

    (University of Science and Technology of China)

  • Songwen Luo

    (University of Science and Technology of China)

  • Meifang Tang

    (University of Science and Technology of China
    Hefei Comprehensive National Science Center)

  • Nianping Liu

    (University of Science and Technology of China)

  • Chen Jiang

    (University of Science and Technology of China
    Hefei Comprehensive National Science Center)

  • Jingwen Fang

    (University of Science and Technology of China
    Xiaoshan Innovation Polis)

  • Shouzhen Li

    (University of Science and Technology of China)

  • Yanbing Hou

    (University of Science and Technology of China)

  • Chuang Guo

    (University of Science and Technology of China
    Bengbu Medical University
    University of Science and Technology of China)

  • Kun Qu

    (University of Science and Technology of China
    Hefei Comprehensive National Science Center
    University of Science and Technology of China)

Abstract

Extrachromosomal circular DNA (eccDNA) is crucial in oncogene amplification, gene transcription regulation, and intratumor heterogeneity. While various analysis pipelines and experimental methods have been developed for eccDNA identification, their detection efficiencies have not been systematically assessed. To address this, we evaluate the performance of 7 analysis pipelines using seven simulated datasets, in terms of accuracy, identity, duplication rate, and computational resource consumption. We also compare the eccDNA detection efficiency of 7 experimental methods through twenty-one real sequencing datasets. Here, we show that Circle-Map and Circle_finder (bwa-mem-samblaster) outperform the other short-read pipelines. However, Circle_finder (bwa-mem-samblaster) exhibits notable redundancy in its outcomes. CReSIL is the most effective pipeline for eccDNA detection in long-read sequencing data at depths higher than 10X. Moreover, long-read sequencing-based Circle-Seq shows superior efficiency in detecting copy number-amplified eccDNA over 10 kb in length. These results offer valuable insights for researchers in choosing the suitable methods for eccDNA research.

Suggested Citation

  • Xuyuan Gao & Ke Liu & Songwen Luo & Meifang Tang & Nianping Liu & Chen Jiang & Jingwen Fang & Shouzhen Li & Yanbing Hou & Chuang Guo & Kun Qu, 2024. "Comparative analysis of methodologies for detecting extrachromosomal circular DNA," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53496-8
    DOI: 10.1038/s41467-024-53496-8
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    References listed on IDEAS

    as
    1. Yuangao Wang & Meng Wang & Mohamed Nadhir Djekidel & Huan Chen & Di Liu & Frederick W. Alt & Yi Zhang, 2021. "eccDNAs are apoptotic products with high innate immunostimulatory activity," Nature, Nature, vol. 599(7884), pages 308-314, November.
    2. Fu Yang & Weijia Su & Oliver W. Chung & Lauren Tracy & Lu Wang & Dale A. Ramsden & ZZ Zhao Zhang, 2023. "Retrotransposons hijack alt-EJ for DNA replication and eccDNA biogenesis," Nature, Nature, vol. 620(7972), pages 218-225, August.
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