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ATACAmp: a tool for detecting ecDNA/HSRs from bulk and single-cell ATAC-seq data
Hansen Cheng1, Wenhao Ma1, Kun Wang1
1Center of Growth, Metabolism, and Aging, Key Laboratory of Bio-Resources and Eco-Environment, College of Life Sciences, Sichuan University, No.29 Wangjiang Road, Chengdu, Sichuan, 610064, China.
BMC Genomics
|November 10, 2023
Summary
A new algorithm, ATACAmp, accurately identifies extrachromosomal DNA (ecDNA) and homogeneously staining regions (HSRs) using ATAC-seq data. This method offers a more accurate and cost-effective alternative to current whole genome sequencing approaches for cancer genome analysis.
Area of Science:
- Genomics
- Cancer Biology
- Bioinformatics
Background:
- High oncogene expression drives tumor progression and drug resistance.
- Extrachromosomal DNA (ecDNA) and homogeneously staining regions (HSRs) amplify oncogenes, leading to poor prognosis.
- Existing ecDNA detection methods using whole genome sequencing (WGS) often yield false positives due to chromosomal DNA interference.
Purpose of the Study:
- To develop and validate a novel algorithm, ATACAmp, for accurate identification of ecDNA/HSRs.
- To leverage ATAC-seq data for improved ecDNA detection, minimizing chromosomal DNA interference.
- To provide a more accessible and cost-effective tool for analyzing ecDNA in cancer genomes.
Main Methods:
- Developed the ATACAmp algorithm utilizing ATAC-seq data to identify ecDNA/HSRs.
- Validated ATACAmp using ATAC-seq data from cell lines with experimentally confirmed ecDNA.
- Compared ATACAmp's performance against AmpliconArchitect (WGS-based) and Circle-finder (ATAC-seq based).
Main Results:
- ATACAmp accurately identified the majority of validated ecDNA regions.
- ATACAmp demonstrated higher accuracy than AmpliconArchitect and Circle-finder.
- ATACAmp successfully analyzed single-cell ATAC-seq data, linking ecDNA to specific cells.
Conclusions:
- ATACAmp provides a novel, accurate, and distinct analytical approach for ecDNA/HSR detection using ATAC-seq data.
- This method reduces the cost and technical complexity associated with ecDNA analysis.
- ATACAmp is freely available as an open-source Python tool.
