Division of Nephrology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Raymond G. Perelman Center for Cellular and Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Mol Oncol. 2019 Apr;13(4):829-839. doi: 10.1002/1878-0261.12435. Epub 2019 Feb 23.
Next-generation sequencing provides an opportunity to detect viral species from RNA-seq data of human tissues, but existing computational approaches do not perform optimally on clinical samples. We developed a bioinformatic method called VirTect for detecting viruses in neoplastic human tissues using RNA-seq data. Here, we used VirTect to analyze RNA-seq data from 363 head and neck squamous cell carcinoma (HNSCC) patients and identified 22 human papillomavirus (HPV)-induced HNSCCs. These predictions were validated by manual review of pathology reports on histopathologic specimens. VirTect showed better performance in recall and accuracy compared to the two existing prediction methods, VirusFinder and VirusSeq, in identifying viral sequences from RNA-seq data. The majority of HPV carcinogenesis studies thus far have been performed on cervical cancer and generalized to HNSCC. Our results suggest that carcinogenesis of HPV-induced HNSCC and other cases of HNSCC involve different genes, so understanding the underlying molecular mechanisms will have a significant impact on therapeutic approaches and outcomes. In summary, RNA-seq together with VirTect can be an effective solution for the detection of viruses from tumor samples and can facilitate the clinicopathologic characterization of various types of cancers with broad applications for oncology.
下一代测序为从人体组织的 RNA-seq 数据中检测病毒物种提供了机会,但现有的计算方法在临床样本上的表现并不理想。我们开发了一种名为 VirTect 的生物信息学方法,用于使用 RNA-seq 数据检测肿瘤组织中的病毒。在这里,我们使用 VirTect 分析了 363 例头颈部鳞状细胞癌(HNSCC)患者的 RNA-seq 数据,并鉴定出 22 例人乳头瘤病毒(HPV)诱导的 HNSCC。这些预测通过对组织病理学标本的病理报告进行手动审查进行了验证。与现有的两种预测方法 VirusFinder 和 VirusSeq 相比,VirTect 在从 RNA-seq 数据中识别病毒序列方面具有更好的召回率和准确性。迄今为止,大多数 HPV 致癌研究都是在宫颈癌上进行的,并推广到 HNSCC。我们的结果表明,HPV 诱导的 HNSCC 和其他 HNSCC 病例的致癌作用涉及不同的基因,因此了解潜在的分子机制将对治疗方法和结果产生重大影响。总之,RNA-seq 结合 VirTect 可以有效地从肿瘤样本中检测病毒,并有助于各种癌症的临床病理特征分析,在肿瘤学中有广泛的应用。