Aperture: alignment-free detection of structural variations and viral integrations in circulating tumor DNA
Aperture: alignment-free detection of structural variations and viral integrations in circulating tumor DNA
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DOI：
10.1093/bib/bbab290
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发表时间：
2021-08-09
影响因子：
9.5
通讯作者：
Wang, Xiaoyue
中科院分区：
文献类型：
--
作者：
Liu, Hongchao;Yin, Huihui;Wang, Xiaoyue
循环肿瘤DNA（ctDNA）中结构变异（SV）和病毒整合的鉴定是精确肿瘤学的关键步骤，可以帮助临床医生进行治疗选择和监测。然而，由于ctDNA的短片段大小，准确检测ctDNA测序数据中的低频SV或涉及复杂连接的SV具有挑战性。在这里，我们描述了光圈，一个新的快速SV调用者，适用于一个独特的策略，基于mer的搜索，二进制标记的断点检测和候选聚类检测SV和病毒的整合具有高灵敏度，特别是当路口跨越重复区域。光圈还采用了基于条形码的过滤器，以确保特异性。与现有方法相比，Aperture在模拟、参考和真实的数据测试中表现出优越的上级灵敏度和特异性，尤其是在低稀释度下。此外，Aperture还能够预测病毒整合位点，并识别涉及真实的患者数据中的新型插入和重复序列的复杂SV。Aperture可在https://github.com/liuhc8/Aperture免费获得。
The identification of structural variations (SVs) and viral integrations in circulating tumor DNA (ctDNA) is a key step in precision oncology that may assist clinicians in treatment selection and monitoring. However, due to the short fragment size of ctDNA, it is challenging to accurately detect low-frequency SVs or SVs involving complex junctions in ctDNA sequencing data. Here, we describe Aperture, a new fast SV caller that applies a unique strategy of -mer-based searching, binary label-based breakpoint detection and candidate clustering to detect SVs and viral integrations with high sensitivity, especially when junctions span repetitive regions. Aperture also employs a barcode-based filter to ensure specificity. Compared with existing methods, Aperture exhibits superior sensitivity and specificity in simulated, reference and real data tests, especially at low dilutions. Additionally, Aperture is able to predict sites of viral integration and identify complex SVs involving novel insertions and repetitive sequences in real patient data. Aperture is freely available at https://github.com/liuhc8/Aperture.