Circle-Map

Circle-Map detects and maps circular DNAs at single-nucleotide resolution by realigning short-read sequencing reads that span circular junctions.

Key Features:

• Single-nucleotide resolution: Detects and maps circular DNAs with breakpoint precision at single-nucleotide resolution.
• Probabilistic realignment model: Implements a probabilistic model to guide the realignment of partially aligned reads.
• Discordant-read utilization: Utilizes information from discordantly mapped reads to accurately align short unaligned read segments spanning circle junctions.
• Handles mappable and non-mappable regions: Detects extrachromosomal DNA circles formed from both mappable and non-mappable regions of a genome.
• Short-read sequencing support: Specifically addresses alignment failures caused by short-read sequencing technologies for reads spanning circular junctions.
• Circular DNA and RNA detection: Has been evaluated for detection of circular DNAs and RNAs in sequencing datasets.
• Performance: Demonstrates increased sensitivity while maintaining high precision on simulated and real datasets.
• Implementation: Implemented as a Python-based package.

Scientific Applications:

• Extrachromosomal DNA analysis: Identification and mapping of extrachromosomal DNA circles in genomic studies, including human tissues.
• Cancer and normal tissue studies: Investigation of circular DNA roles in normal and cancerous conditions using sequencing data.
• Circular RNA and DNA discovery: Detection of circular RNAs and DNAs in next-generation sequencing experiments.
• Method benchmarking: Comparative evaluation and benchmarking of circular DNA/RNA detection methods on simulated and real datasets.

Methodology:

Uses a probabilistic model to guide realignment of partially aligned reads and leverages discordantly mapped reads to place short unaligned read portions, enabling single-nucleotide resolution mapping of circular DNA junctions.