Detection and Validation of Circular DNA Fragments Using Nanopore Sequencing.

Autor:	Tüns AI; Laboratory of Molecular Oncology, West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Essen, Germany., Hartmann T; Algorithms for Reproducible Bioinformatics, Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Magin S; Institute for Artificial Intelligence in Medicine, IKIM, University Hospital Essen, Essen, Germany., González RC; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Max-Delbrück-Centrum für Molekulare Medizin (BIMSB/BIH), Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Experimental and Clinical Research Center (ECRC) of the MDC and Charité Berlin, Essen, Germany., Henssen AG; Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.; Max-Delbrück-Centrum für Molekulare Medizin (BIMSB/BIH), Berlin, Germany.; Berlin Institute of Health, Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany.; Experimental and Clinical Research Center (ECRC) of the MDC and Charité Berlin, Essen, Germany., Rahmann S; Center for Bioinformatics and Department of Computer Science, Saarland University, Saarbrücken, Germany., Schramm A; Laboratory of Molecular Oncology, West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Essen, Germany., Köster J; Algorithms for Reproducible Bioinformatics, Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2022 May 30; Vol. 13, pp. 867018. Date of Electronic Publication: 2022 May 30 (Print Publication: 2022).
DOI:	10.3389/fgene.2022.867018
Abstrakt:	Occurrence of extra-chromosomal circular DNA is a phenomenon frequently observed in tumor cells, and the presence of such DNA has been recognized as a marker of adverse outcome across cancer types. We here describe a computational workflow for identification of DNA circles from long-read sequencing data. The workflow is implemented based on the Snakemake workflow management system. Its key step uses a graph-theoretic approach to identify putative circular fragments validated on simulated reads. We then demonstrate robustness of our approach using nanopore sequencing of selectively enriched circular DNA by highly sensitive and specific recovery of plasmids and the mitochondrial genome, which is the only circular DNA in normal human cells. Finally, we show that the workflow facilitates detection of larger circular DNA fragments containing extrachromosomal copies of the MYCN oncogene and the respective breakpoints, which is a potentially useful application in disease monitoring of several cancer types. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Tüns, Hartmann, Magin, González, Henssen, Rahmann, Schramm and Köster.)
Databáze:	MEDLINE
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