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This study systematically assessed extrachromosomal circular DNA (eccDNA) detection tools. Circle-Map and Circle_finder showed strong performance in short-read analysis, while CReSIL excelled in long-read eccDNA identification.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • Extrachromosomal circular DNA (eccDNA) plays a key role in cancer development, influencing oncogene amplification, gene transcription, and tumor heterogeneity.
  • Numerous computational pipelines and experimental techniques exist for eccDNA identification, but their comparative performance remains unevaluated.

Purpose of the Study:

  • To systematically evaluate the detection efficiency and performance of various bioinformatics pipelines and experimental methods for identifying eccDNA.
  • To provide guidance for researchers selecting optimal tools for eccDNA analysis.

Main Methods:

  • Performance assessment of 7 short-read and long-read eccDNA analysis pipelines using simulated datasets, focusing on accuracy, identity, duplication rates, and computational demands.
  • Comparative analysis of 7 experimental methods for eccDNA detection using 21 real sequencing datasets.

Main Results:

  • Circle-Map and Circle_finder (bwa-mem-samblaster) demonstrated superior performance among short-read pipelines, though Circle_finder exhibited redundancy.
  • CReSIL emerged as the most effective pipeline for long-read eccDNA detection at sequencing depths >10X.
  • Long-read sequencing with Circle-Seq proved highly efficient for detecting copy number-amplified eccDNA longer than 10 kb.

Conclusions:

  • The study highlights the strengths and weaknesses of different eccDNA detection methodologies.
  • Findings offer crucial insights for researchers to select appropriate bioinformatics and experimental approaches for their specific eccDNA research needs.