Bioinformatics Studies of Human Viruses

人类病毒的生物信息学研究

• 批准号: 8558093
• 负责人: John Spouge
• 金额: $ 23.86万
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8558093
• 关键词: Animal Model; Bioinformatics; Consult; DNA; DNA Viruses; Databases; Detection; Frequencies; Genes; Genetic Transcription; Genome; HIV; Health; Herpesviridae; Horizontal Gene Transfer; Human; Human Genome; Human Virology; Human Virus; Institutes; Macaca; Manuscripts; Methods; Modeling; Problem Solving; Proteins; RNA Viruses; Running; SIV; Sequence Analysis; Surveys; System; Tertiary Protein Structure; Viral; Viral Genome; Viral Proteins; Virion; Virus; Virus Diseases; programs; viral RNA

Dr. Gonzalez-Delgado set up a semi-automated pipeline using the alignment program HMMer and the Pfam protein domain database, to identify the functionality of viral proteins. The pipeline takes the genome of a human virus, extracts the annotated genes, and runs HMMer to find the domains composing a viral protein. Once statistically significant Pfam domains have been found, Pfam is again queried, to discover which of the proteins contributing to a given domain are human. The human proteins become candidates for a previous horizontal gene transfer between the virus and its human host. To inform the project with questions relevant to experimental virologists, Dr. Gonzalez-Delgado consulted with Drs. DeVico and Lewis, human immunodeficiency virus (HIV) experts at the Institute of Human Virology. The project has resulted in a submitted manuscript examining human herpes virus 8 (HHV-8) as a model virus, where HGT with the human genome are relatively well characterized. HHV-8 shares at least 36% of its genes with the human host: 17 known and 12 potentially new genes were identified as candidates for HGT, despite previous intense experimental scrutiny. To compare the frequency of HGT across viruses, the manscript surveyed 10 other viruses impacting human health, concluding that HGT probably occurs between humans and both DNA and RNA viruses, in viral genomes of differing sizes, regardless of DNA transcription strategies. Of special note are the Human T-lymphotropic viruses, where genes involved in HGT possibly have a frequency as high as 73%. Dr. Gonzalez-Delgado is now analyzing sequences of the simian immunodeficiency virus, which infects macaques. The SIV-macaque system provides an animal model for HIV infection, to answer a question posed by Drs. Lewis and Devico: are the sequences of the infecting and non-infecting HIV particles in a viral inoculum statistically distinguishable?

Gonzalez-Delgado博士使用比对程序HMMer和Pfam蛋白质结构域数据库建立了一个半自动化的流水线，以识别病毒蛋白质的功能。该管道获取人类病毒的基因组，提取注释的基因，并运行HMMer来找到组成病毒蛋白的结构域。一旦发现具有统计学显著性的Pfam结构域，再次查询Pfam，以发现对给定结构域有贡献的蛋白质中的哪些是人类的。人类蛋白质成为病毒与其人类宿主之间先前水平基因转移的候选者。为了向该项目提供与实验病毒学家有关的问题，Gonzalez-Delgado博士咨询了人类病毒学研究所的人类免疫缺陷病毒（HIV）专家DeVico和刘易斯博士。 该项目已经提交了一份手稿，将人类疱疹病毒8（HHV-8）作为模型病毒进行研究，其中HGT与人类基因组的特征相对较好。HHV-8与人类宿主至少有36%的基因相同：17个已知基因和12个潜在的新基因被确定为HGT的候选基因，尽管之前进行了严格的实验审查。为了比较HGT在不同病毒中的频率，Manscript调查了其他10种影响人类健康的病毒，得出的结论是HGT可能发生在人类与DNA和RNA病毒之间，在不同大小的病毒基因组中，无论DNA转录策略如何。特别值得注意的是人类嗜T淋巴细胞病毒，其中涉及HGT的基因可能具有高达73%的频率。 博士冈萨雷斯-德尔加多现在正在分析感染猕猴的猿免疫缺陷病毒的序列。SIV-猕猴系统提供了一种HIV感染的动物模型，以回答刘易斯和Devico博士提出的一个问题：病毒接种物中感染性和非感染性HIV颗粒的序列在统计学上是可区分的吗？