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

Abstract

BackgroundCircular 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.ResultsHere, 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.ConclusionCircle-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 https://github.com/iprada/Circle-Map.

Extrachromosomal DNA amplicons in antimalarial‐resistant Plasmodium falciparum

“…Improved detection methods, including new efforts to computationally identify circular DNA from sequencing data (Deshpande et al, 2019;Prada-Luengo et al, 2019;Wu et al, 2019), hold promise for future studies of malaria ecDNA.…”

ECCsplorer: a pipeline to detect extrachromosomal circular DNA (eccDNA) from next-generation sequencing data

“…To our knowledge there are currently three software solutions to detect eccDNAs. Circle-Map (Prada-Luengo et al ., 2019) is a realigning-based pipeline to detect eccDNA from circSeq datasets already mapped to a reference genome sequence. Two further tools are available, though their very different application ranges prevent a direct comparison.…”

“…Comparison of the results from ECCsplorer pipeline (described here) with the Circle-Map (Prada-Luengo et al ., 2019) and the originally published eccDNA candidates from A. thaliana (Lanciano et al ., 2017) and H. sapiens (Møller et al ., 2018). …”

“…Lanciano et al ., 2021). Computationally, new eccDNA candidates are currently identified based on typical read signatures, commonly detected by the mapping against a reference genome (Lanciano et al ., 2017; Prada-Luengo et al ., 2019). These characteristic signatures include split and discordant mapping reads, which result when mapping a circular sequence against a linear reference.…”

Sequencing of methylase-accessible regions in integral circular extrachromosomal DNA reveals differences in chromatin structure

“…Some attempts have been made to solve the ecDNA identification in sequencing data by improved algorithms. Most algorithms relied on the detection of ecDNA junction sequence, such as Circle-Map [10], AA (ampliconarchict) [11], CIRC_finder[12], and others [13]. With the aid of these methods, the ecDNA was identified in numerous cancer tissues [12, 14, 15] [16] [5], aging cells [17], plasma [18, 19], and healthy somatic tissues [20].…”