Table_2_Multiple HPV integration mode in the cell lines based on long-reads sequencing.XLS

BackgroundThe integration of human papillomavirus (HPV) is closely related to the occurrence of cervical cancer. However, little is known about the complete state of HPV integration into the host genome.MethodsIn this study, three HPV-positive cell lines, HeLa, SiHa, and CaSki, were subjected to NANOPORE long-read sequencing to detect HPV integration. Analysis of viral integration patterns using independently developed software (HPV-TSD) yielded multiple complete integration patterns for the three HPV cell lines.ResultsWe found distinct differences between the integration patterns of HPV18 and HPV16. Furthermore, the integration characteristics of the viruses were significantly different, even though they all belonged to HPV16 integration. The HPV integration in the CaSki cells was relatively complex. The HPV18 integration status in HeLa cells was the dominant, whereas the percentage of integrated HPV 16 in SiHa and CaSki cells was significantly lower. In addition, the virus sequences in the HeLa cells were incomplete and existed in an integrated state. We also identified a large number of tandem repeats in HPV16 and HPV18 integration. Our study not only clarified the feasibility of high-throughput long-read sequencing in the study of HPV integration, but also explored a variety of HPV integration models, and confirmed that viral integration is an important form of HPV in cell lines.ConclusionElucidating HPV integration patterns will provide critical guidance for developing a detection algorithm for HPV integration, as well as the application of virus integration in clinical practice and drug research and development.

背景：人乳头瘤病毒（HPV）的整合与宫颈癌的发生密切相关。然而，关于HPV整合至宿主基因组中的完整状态，知之甚少。方法：在本研究中，选取了三种HPV阳性细胞系，即HeLa、SiHa和CaSki，采用NANOPORE长读长测序技术检测HPV整合。通过自行开发的软件（HPV-TSD）分析病毒整合模式，对三种HPV细胞系产生了多种完整的整合模式。结果：我们发现在HPV18和HPV16的整合模式之间存在显著差异。此外，尽管它们均属于HPV16整合，病毒的整合特性仍存在显著差异。CaSki细胞中的HPV整合相对复杂。HeLa细胞中HPV18的整合状态占主导地位，而SiHa和CaSki细胞中整合的HPV16比例显著较低。此外，HeLa细胞中的病毒序列不完整，存在于整合状态。我们还识别出大量HPV16和HPV18整合中的串联重复序列。本研究不仅阐明了高通量长读长测序在研究HPV整合中的可行性，而且探索了多种HPV整合模型，并证实病毒整合是细胞系中HPV的重要形式。结论：阐明HPV整合模式将为开发HPV整合检测算法提供关键指导，并有助于病毒整合在临床实践及药物研发中的应用。