GII.4诺如病毒全基因组共发生网络的构建和分析

发布时间：2018-02-15 12:07

本文关键词： GII.4诺如病毒共发生网络基因组进化　出处：《南华大学》2012年硕士论文　论文类型：学位论文

【摘要】：目的：利用生物信息学方法建立GII.4型诺如病毒的进化模型，探讨1974年至2010年世界范围GII.4诺如病毒的进化机制和动力学规律，找出影响GII.4诺如病毒进化的重要氨基酸位点，为预防和控制诺如病毒胃肠炎的暴发流行提供基础数据。方法：通过构建核苷酸共发生网络（Co-occurrence Network）来分析GII.4型诺如病毒进化的潜在模式。利用软件Muscle比对233条1974年至2010年来自9个国家的GII.4诺如病毒全基因组序列；去除其中的保守核苷酸位点，从不保守位点中提取出呈现完美共发生现象的核苷酸对，连接所有的完美共发生核苷酸对，，利用软件Cytoscape显示共发生网络并计算网络拓扑特征；进一步编程将网络中的核苷酸对聚类成共发生核苷酸模块，使用软件Expander分析每一个共发生核苷酸模块并从中提取出能揭示病毒的生物学活性的具有协同作用的共变异核苷酸。结果： 1. GII.4诺如病毒基因组核苷酸替代分析发现病毒核苷酸序列变异数随着时间不断增加，表明诺如病毒的进化是随时间蓄积的。 2.共发生网络连接度分析表明GII.4诺如病毒网络连接度的变化可以定量地反映病毒抗原性的变化，当网络连接度在某一季节出现了变化高峰时，意味着新的病毒变异株的出现及疫情暴发的可能；网络连接度的分析结果与传统的系统进化分析结果一致。 3.基因片段的分析显示在GII.4诺如病毒进化过程中，基因组内的各个基因片段都起着相应的推动作用，即病毒的进化是全基因组水平上的共进化。 4.通过对共发生核苷酸模块的分析，找到了诺如病毒基因组的各个基因片段中对于病毒进化起关键作用的相应氨基酸位点。结论： 1.核苷酸共发生网络模型是分析病毒进化的一种既简单又准确的方法，它可以作为传统系统进化分析方法的一个补充，并可以对诺如病毒疫情的暴发提供有效的预警。 2. GII.4病毒的进化是基因组水平上的共进化。 3.基因组中与病毒受体结合部位表现出共进化关系的氨基酸位点对病毒的进化作用可能更大，仍需定点突变实验证实。
[Abstract]:Objective: to establish an evolutionary model of GII.4 type norovirus by bioinformatics, and to explore the evolutionary mechanism and kinetics of GII.4 norovirus from 1974 to 2010, and to find out the important amino acid sites that affect the evolution of GII.4 norovirus. Provide basic data to prevent and control the outbreak of norovirus gastroenteritis. Methods: to analyze the potential model of GII.4 type Norovirus evolution by constructing co-occurrence network of nucleotide co-occurrence network. The whole genome sequence of GII.4 Norovirus from 1974 to 2010 was compared with the software Muscle. Removing the conserved nucleotide sites and extracting the perfect co-occurrence nucleotide pairs from the unconserved sites, connecting all the perfect co-occurrence nucleotide pairs, using the software Cytoscape to display the co-occurrence network and calculate the network topology characteristics; Further programming the nucleotide pairs in the network to cluster into co-nucleotide modules and using software Expander to analyze each co-nucleotide module and extract covariant nucleotides with synergistic effect which can reveal the biological activity of the virus. Results:. 1. Nucleotide substitution analysis of GII.4 norovirus genome showed that the variation of nucleotide sequence increased with time, indicating that the evolution of norovirus accumulated over time. 2. The analysis of cooccurrence network connectivity shows that the change of network connectivity of GII.4 Norovirus can reflect the change of virus antigenicity quantitatively, and when the network connectivity reaches its peak in a certain season, This means the emergence of new virus variants and the possibility of outbreak. The results of network connectivity analysis are consistent with the results of traditional phylogenetic analysis. 3. The analysis of gene fragments shows that in the evolution of GII.4 Norovirus, each gene fragment in the genome plays a corresponding role, that is, the evolution of the virus is coevolution at the whole genome level. 4. Based on the analysis of cooccurrence nucleotide modules, the corresponding amino acid sites which play a key role in the evolution of Noroviruses were found in each gene fragment of Norovirus genome. Conclusion:. 1. The nucleotide cooccurrence network model is a simple and accurate method to analyze virus evolution. It can be used as a supplement to the traditional phylogenetic analysis method and can provide an effective early warning for the outbreak of Norovirus. 2. The evolution of GII.4 virus is coevolution at genome level. 3. The coevolution of amino acid sites in genomes with coevolutionary relationship with viral receptor sites may be more important for virus evolution, which still needs to be confirmed by site-directed mutation experiments.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R373

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