环状染色体外 DNA (ecDNA) 是一种癌基因扩增形式，存在于各种癌症类型中，与患者的不良预后相关。 ecDNA 结构可能很复杂，并且包含源自多个染色体位置的重排 DNA 序列。由于 ecDNA 的结构可以影响癌基因调控并可能表明其形成机制，因此以高分辨率将其与测序数据分开至关重要。尽管已经开发出在癌症基因组测序中识别和重建 ecDNA 的方法，但解析复杂的 ecDNA 结构仍然具有挑战性，特别是具有共享基因组足迹的扩增子。我们在此介绍 Decoil，这是一种计算方法，它将断点图方法与回归相结合，以重建复杂的 ecDNA，并对共存的 ecDNA 元素与长读长纳米孔测序中重叠的基因组足迹进行去卷积。对于简单和复杂的 ecDNA，在模拟长读长测序数据中，Decoil 的性能优于基于从头组装和比对的方法。将Decoil应用于全基因组测序数据发现了不同的ecDNA拓扑，并探索了神经母细胞瘤和细胞系中的ecDNA结构异质性，表明该方法可以改善癌症中的ecDNA结构分析。由冷泉港实验室出版社出版。

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 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.Published by Cold Spring Harbor Laboratory Press.