Sensitive detection of circular DNAs at single-nucleotide resolution using guided realignment of partially aligned reads

Background Circular DNA has recently been identified across different species including human normal and cancerous tissue, but short-read mappers are unable to align many of the reads crossing circle junctions hence limiting their detection from short-read sequencing data. Results Here, we propose a new method, Circle-Map that guides the realignment of partially aligned reads using information from discordantly mapped reads to map the short unaligned portions using a probabilistic model. We compared Circle-Map to similar up-to-date methods for circular DNA and RNA detection and we demonstrate how the approach implemented in Circle-Map dramatically increases sensitivity for detection of circular DNA on both simulated and real data while retaining high precision. Conclusion Circle-Map is an easy-to-use command line tool that implements the required pipeline to accurately detect circular DNA from circle enriched next generation sequencing experiments. Circle-Map is implemented in python3.6 and it is freely available at .