Wang Qingguo, Jia Peilin, Zhao Zhongming
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37203 USA.
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37203 USA ; Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN 37232 USA.
Genome Med. 2015 Jan 20;7(1):2. doi: 10.1186/s13073-015-0126-6. eCollection 2015.
Fueled by widespread applications of high-throughput next generation sequencing (NGS) technologies and urgent need to counter threats of pathogenic viruses, large-scale studies were conducted recently to investigate virus integration in host genomes (for example, human tumor genomes) that may cause carcinogenesis or other diseases. A limiting factor in these studies, however, is rapid virus evolution and resulting polymorphisms, which prevent reads from aligning readily to commonly used virus reference genomes, and, accordingly, make virus integration sites difficult to detect. Another confounding factor is host genomic instability as a result of virus insertions. To tackle these challenges and improve our capability to identify cryptic virus-host fusions, we present a new approach that detects Virus intEgration sites through iterative Reference SEquence customization (VERSE). To the best of our knowledge, VERSE is the first approach to improve detection through customizing reference genomes. Using 19 human tumors and cancer cell lines as test data, we demonstrated that VERSE substantially enhanced the sensitivity of virus integration site detection. VERSE is implemented in the open source package VirusFinder 2 that is available at http://bioinfo.mc.vanderbilt.edu/VirusFinder/.
在高通量下一代测序（NGS）技术的广泛应用以及应对致病性病毒威胁的迫切需求推动下，最近开展了大规模研究，以调查病毒在可能导致致癌或其他疾病的宿主基因组（例如人类肿瘤基因组）中的整合情况。然而，这些研究中的一个限制因素是病毒的快速进化以及由此产生的多态性，这使得读取序列难以轻松比对到常用的病毒参考基因组，因此，病毒整合位点难以检测。另一个混杂因素是病毒插入导致的宿主基因组不稳定。为应对这些挑战并提高我们识别隐秘病毒 - 宿主融合的能力，我们提出了一种通过迭代参考序列定制（VERSE）来检测病毒整合位点的新方法。据我们所知，VERSE是第一种通过定制参考基因组来提高检测能力的方法。使用19个人类肿瘤和癌细胞系作为测试数据，我们证明VERSE显著提高了病毒整合位点检测的灵敏度。VERSE在开源软件包VirusFinder 2中实现，可在http://bioinfo.mc.vanderbilt.edu/VirusFinder/获取。
