Decoil: Reconstructing Extrachromosomal DNA Structural Heterogeneity from Long-Read Sequencing Data

Giurgiu M, Wittstruck N, Rodriguez-Fos E, González RC, Brückner L, Krienelke-Szymansky A, Helmsauer K, Hartebrodt A, Euskirchen P, Koche RP, Haase K, Reinert K, Henssen AG (2024)

Publication Language: English

Publication Type: Conference contribution

Publication year: 2024

Journal

Lecture Notes in Computer Science Springer Verlag

Publisher: Springer Nature

Series: Lecture Notes in Computer Science

City/Town: Cham

Book Volume: 14758

Pages Range: 406-411

Conference Proceedings Title: Research in Computational Molecular Biology. 28th Annual International Conference, RECOMB 2024, Cambridge, MA, USA, April 29–May 2, 2024, Proceedings

Event location: Cambridge, MA US

ISBN: 9781071639887

DOI: 10.1007/978-1-0716-3989-4_41

Abstract

Circular extrachromosomal DNA (ecDNA) is a form of oncogene amplification found across cancer types and associated with poor outcome in patients. EcDNA can be structurally complex and contain rearranged DNA sequences derived from multiple chromosome locations. As the structure of ecDNA can impact oncogene regulation and may indicate mechanisms of its formation, disentangling it at high resolution from sequencing data is essential. Even though methods have been developed to identify and reconstruct ecDNA in cancer genome sequencing, it remains challenging to resolve complex ecDNA structures, in particular amplicons with shared genomic footprints. We here introduce Decoil, a computational method which combines a breakpoint-graph approach with LASSO regression to reconstruct complex ecDNA and deconvolve co-occurring ecDNA elements with overlapping genomic footprints from long-read nanopore sequencing. Decoil outperforms de-novo assembly and alignment-based methods in simulated long-read sequencing data for both simple and complex ecDNAs. Applying Decoil on whole genome sequencing data uncovered different ecDNA topologies and explored ecDNA structure heterogeneity in neuroblastoma tumors and cell lines, indicating that this method may improve ecDNA structural analyzes in cancer.

Authors with CRIS profile

Anne Hartebrodt Professur für Biomedical Network Science

Involved external institutions

Freie Universität Berlin DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Memorial Sloan Kettering Cancer Center US United States (USA) (US)

How to cite

APA:

Giurgiu, M., Wittstruck, N., Rodriguez-Fos, E., González, R.C., Brückner, L., Krienelke-Szymansky, A.,... Henssen, A.G. (2024). Decoil: Reconstructing Extrachromosomal DNA Structural Heterogeneity from Long-Read Sequencing Data. In Jian Ma (Eds.), Research in Computational Molecular Biology. 28th Annual International Conference, RECOMB 2024, Cambridge, MA, USA, April 29–May 2, 2024, Proceedings (pp. 406-411). Cambridge, MA, US: Cham: Springer Nature.

MLA:

Giurgiu, Mădălina, et al. "Decoil: Reconstructing Extrachromosomal DNA Structural Heterogeneity from Long-Read Sequencing Data." Proceedings of the 28th International Conference on Research in Computational Molecular Biology, RECOMB 2024, Cambridge, MA Ed. Jian Ma, Cham: Springer Nature, 2024. 406-411.

BibTeX: Download