Welcome to Circle-Map official repository!

Circle-Map is an easy to install, python package that implements all the steps required to detect extrachromosomal DNA circles. The package contains easy to run algorithms to accurately detect circular DNA formed from mappable and non mappable regions of a genome.

Why should I use Circle-Map?

Circle-Map takes as input an alignment of reads to a reference genome (e.g. a BWA-MEM generated BAM file) and like other methods, it will use those alignments to detect cases were the read has been split into two segments (e.g. split reads) to detect genomic rearrangements supporting a circular DNA structure.

However, this approach results in many split read alignments being missed because the aligner is not able to map both split segments of the read, either because they are too short or because they align to too many places. In this cases, the aligner will report a read alignment containing some of the bases unmapped (e.g soft-clipped reads).

Unlike other methods, Circle-Map is able to map both segments of the soft-clipped reads by realigning the unmapped parts probabilistically to a graph representation of the circular DNA breakpoints. Which allows for a more accurate detection of the circular DNA breakpoints. In our recent paper (https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-019-3160-3) we show how this approach dramatically increases sensitivity while retaining high precision.

Getting started

Installation

Circle-Map runs on GNU/Linux operating systems, requires >=python3.6 and can be installed and set-up using the following ways:

This will install Circle-Map, and all the external packages required to run every part of Circle-Map software.

Installation using pip:

 python -m pip install Circle-Map

Installation using conda:

 conda install -c bioconda circle-map

Note: If you want to simulate circular DNA short reads, you will need to install BBMap and ART on your system.

Using Circle-Map

Now you are ready to get started detecting circular DNA. We have created a Circle-Map wiki that explains step by step how you can go from your raw sequencing reads to interpretable results. In the wiki, you can try and learn using Circle-Map with the following tutorials:

• Tutorial: identification of mappable circular DNA using Circle Map Realign

• Tutorial: identification of repetitive circular DNA using Circle Map Repeats

Once you have detected circular DNA in your samples you will probably be interested at looking at the output files. To help you understanding the output, we have created a page explaining what is the information provided by Circle-Map in every column of its output. You can find the information in the following link:

• Circle-Map output explanation

Getting help

The best place for getting help, feedback,report bugs or request new features is to post an issue. You can also reach me at xsh723 at dot binf dot ku dot dk

Citing

If you use Circle-Map Realign, please cite:

• Prada-Luengo, I., Krogh, A., Maretty, L. & Regenberg,B. Sensitive detection of circular DNAs at single-nucleotide resolution using guided realignment of partially aligned reads. BMC Bioinformatics 20, 663 (2019) doi:10.1186/s12859-019-3160-3

If you use Circle-Map Repeats please cite:

• Prada-Luengo, I., Møller, H.D., Henriksen, R.A., Gao, Q., Larsen, C..E, Alizadeh, S., Maretty, L., Houseley, J. & Regenberg, B., Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae. Nucleic Acids Research gkaa545, doi:10.1093/nar/gkaa545

License

Circle-Map is freely available under the MIT license

Acknowledgements

Circle-Map is being developed by Iñigo Prada-Luengo, Anders Krogh, Lasse Maretty and Birgitte Regenberg at the University of Copenhagen