circlehunter

circlehunter detects extrachromosomal circular DNA (ecDNA) in ATAC-Seq data to identify ecDNA-associated chromatin accessibility and oncogene amplification in cancer.

Key Features:

• Identification of ecDNA: Leverages enhanced chromatin accessibility signals characteristic of ecDNA to detect circular DNA from ATAC-Seq data.
• High accuracy: Achieves an F1 score of 0.93 on simulated datasets at a local depth of 30× with read lengths as short as 35 base pairs.
• Large-scale application: Applied to 94 publicly available ATAC-Seq datasets to predict 1312 ecDNAs and to identify oncogene-containing circular amplifications.

Scientific Applications:

• Tumorigenesis research: Enables study of ecDNA-driven tumor evolution and intercellular heterogeneity resulting from non-Mendelian inheritance patterns.
• Oncogene amplification analysis: Identifies ecDNA harboring oncogenes such as MYC and characterizes their amplification.
• Therapeutic insight: Links ecDNA-associated oncogene amplification to regulatory effects (e.g., MYC amplification affecting NEUROD1 expression) and to subtype-specific drug sensitivity such as sensitivity to Aurora kinase inhibitors.

Methodology:

Analyzes ATAC-Seq chromatin accessibility signals to detect ecDNA; evaluated on simulated datasets (35 bp reads, local depth 30×) and applied to 94 public ATAC-Seq datasets, yielding 1312 predicted ecDNAs and associated oncogene amplifications.