ECCsplorer: a pipeline to detect extrachromosomal circular DNA (eccDNA) from next-generation sequencing data.

Area of Science:

• Genomics
• Bioinformatics
• Molecular Biology

Background:

• Extrachromosomal circular DNAs (eccDNAs) are prevalent in eukaryotes and implicated in stress, cancer, and aging.
• Investigating eccDNAs is challenging due to a lack of computational tools.

Purpose of the Study:

• To develop a bioinformatics pipeline, ECCsplorer, for automated eccDNA detection.
• To provide a versatile tool for analyzing eccDNAs across diverse organisms and tissues.

Main Methods:

• ECCsplorer utilizes next-generation sequencing data, specifically amplified circular DNA (circSeq).
• It employs read mapping to reference genomes to identify characteristic read distributions (high coverage, discordant mapping, split reads).
• A reference-free comparison of eccDNA reads against control data identifies specifically enriched DNA circles.

Main Results:

• ECCsplorer successfully detected eccDNA candidates in various datasets, including human, Arabidopsis thaliana, and Beta vulgaris.
• The pipeline demonstrated sensitivity and specificity by identifying mitochondrial mini-circles and retrotransposon activation.
• ECCsplorer functions effectively with and without reference genomes.

Conclusions:

• ECCsplorer is a robust bioinformatics pipeline for eccDNA detection in any organism using next-generation sequencing data.
• The identified eccDNA targets facilitate downstream research in cancer genomics, organelle genomics, and transposable element analysis.