ATACAmp

ATACAmp detects extrachromosomal DNA (ecDNA) and homogeneously staining regions (HSRs) in tumor genomes from ATAC-seq data to characterize oncogene amplification and its associations with tumor progression and drug resistance.

Key Features:

• Utilization of ATAC-seq Data: Leverages chromatin accessibility patterns in bulk ATAC-seq to detect ecDNA and HSRs while reducing interference from chromosomal DNA.
• Single-Cell Analysis Capability: Processes single-cell ATAC-seq data to assign ecDNA occurrences to individual cells for analysis of cellular heterogeneity and oncogene amplification dynamics.
• High Accuracy and Validation: Validated on ATAC-seq data from cell lines with experimentally confirmed ecDNA and shown in comparative analyses to outperform AmpliconArchitect (WGS) and Circle-finder (ATAC-seq) for identifying known ecDNA regions.
• Implementation: Implemented in Python.

Scientific Applications:

• ecDNA and HSR Detection: Identification of ecDNA and HSRs in tumor genomes using ATAC-seq-derived accessibility signals.
• Oncogene Amplification Studies: Characterization of oncogene amplification events and their potential roles in tumor progression and drug resistance.
• Single-Cell Heterogeneity Analysis: Linking ecDNA occurrences to individual cells to study intratumoral heterogeneity and amplification dynamics.
• Alternative to WGS-based Methods: Providing an ATAC-seq-based approach that can reduce false positives associated with chromosomal DNA interference compared with WGS-based detection.

Methodology:

Analyzes ATAC-seq data by exploiting elevated chromatin accessibility of ecDNA, was validated on ATAC-seq from cell lines with experimentally confirmed ecDNA, and was benchmarked against AmpliconArchitect and Circle-finder; implemented in Python.