Reconstructing extrachromosomal DNA structural heterogeneity from long-read sequencing data using Decoil

被引：3

作者：

Giurgiu, Madalina ^{[1
,2
,3
,4
]}

Wittstruck, Nadine ^{[1
,2
,3
]}

Rodriguez-Fos, Elias ^{[1
,2
,3
]}

Chamorro Gonzalez, Rocio ^{[1
,2
,3
,5
]}

Brueckner, Lotte ^{[1
,2
,3
,5
]}

Krienelke-Szymansky, Annabell ^{[1
,2
,3
]}

Helmsauer, Konstantin ^{[1
,2
,3
]}

Hartebrodt, Anne ^{[6
]}

Euskirchen, Philipp ^{[7
,8
,9
,10
,11
]}

Koche, Richard P. ^{[12
]}

Haase, Kerstin ^{[1
,2
,3
]}

Reinert, Knut ^{[4
]}

Henssen, Anton G. ^{[1
,2
,3
,5
]}

机构：

[1] Charite Univ Med Berlin, Dept Pediat Oncol & Hematol, D-13353 Berlin, Germany

[2] Max Delbruck Ctr & Charite Berlin, Expt & Clin Res Ctr, D-13125 Berlin, Germany

[3] Charite Univ Med Berlin, D-10117 Berlin, Germany

[4] Free Univ Berlin, D-14195 Berlin, Germany

[5] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

[6] Friedrich Alexander Univ Erlangen Nurnberg, D-91054 Erlangen, Germany

[7] German Canc Consortium DKTK, Partner Site Berlin, Partnership DKFZ, D-10117 Berlin, Germany

[8] Charite Univ Med Berlin, D-10117 Berlin, Germany

[9] Charite Univ Med Berlin, Dept Neuropathol, D-13353 Berlin, Germany

[10] Free Univ Berlin, D-13353 Berlin, Germany

[11] Humboldt Univ, D-13353 Berlin, Germany

[12] Mem Sloan Kettering Canc Ctr, Ctr Epigenet Res, New York, NY 10065 USA

来源：

GENOME RESEARCH | 2024年 / 34卷 / 09期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

DOUBLE MINUTES; CIRCULAR DNA; MODEL;

D O I：

10.1101/gr.279123.124

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 can 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 that 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 analyses in cancer.

引用

页码：1355 / 1364

页数：10

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