Calico Life Sciences LLC 1 article published in JoVE Biology Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells Henrik D. Møller1, Rasmus K. Bojsen2, Chris Tachibana3, Lance Parsons4, David Botstein5, Birgitte Regenberg1 1Department of Biology, University of Copenhagen, 2National Veterinary Institute, Technical University of Denmark, 3Group Health Research Institute, 4Lewis-Sigler Institute for Integrative Genomics, Princeton University, 5Calico Life Sciences LLC This paper presents a sensitive method called Circle-Seq for purifying extrachromosomal circular DNA (eccDNA). The method encompasses column purification, removal of remaining linear chromosomal DNA, rolling-circle amplification and high-throughput sequencing. Circle-Seq is applicable to genome-scale screening of eukaryotic eccDNA and studying genome instability and copy-number variation.