相位残差颗粒数混合高斯模型研究和腺病毒三维重构
发布时间：2018-10-16 11:49
【摘要】：高分辨冷冻电子显微学重构病毒需要大量（颗粒数以万计）冷冻电镜照片，程序处理这些电镜照片耗费大量时间。处理数据的过程中筛选颗粒的方法以及噪声等因素的影响，实际上程序处理的颗粒中有部分颗粒是噪声粒子。在重构中程序处理的批量数据中包含了这些颗粒，颗粒数的增加反映在程序计算用时上是成指数增长。在精修的过程中，相位残差与颗粒数呈现出双高斯峰模型。显然，应用统计学以及重构方法的原因，相位残差和颗粒数图显示分属于两个高斯峰，这些主峰粒子与侧峰粒子是属于两类粒子。本文详细阐述了二十面体病毒三维重构技术的原理、方法和三维重构数据处理流程、算法。通过分析处理颗粒在程序处理数据过程中的变化特点，来了解相位残差颗粒数的混合高斯模型；本文还重构了腺病毒Ad5F35的衣壳结构，揭示了纤维penton base结合守恒，洞悉了纤维与受体之间的相互作用。其具体内容如下： 我们重构了Ad5F35衣壳的三维结构表明腺病毒的纤维penton base结合是守恒的。通过比较Ad5F35密度图的纤维结构和由c终端knob和shaft区组成的虚拟同源Ad35模型的纤维结构，我们证实了纤尾的c终端部分（残留22 43）就是shaft长度的一部分，它位于纤维shaft的主干底部。此外基于我们的Ad5F35结构，即CD46和整合素受体与Ad5F35衣壳的相互作用模型，表明短纤维的Ads可能能够同时绑定受体整合素和CD46。通过处理多套已经发表在国际相关领域的核心期刊上的各类病毒数据，来研究混合高斯模型中两峰间距和病毒结构分辨率的对应关系。用多组数据在不同傅里叶半径下精修，对比分析在相同半径下每轮精修后的结果：对于主峰颗粒，在同一傅里叶半径下，精修次数越多，峰值的位置不变，但是整个峰值颗粒越来越集中在峰值附近；精修次数增加，颗粒的分布几率越来越趋向于峰值附近，，应该是测量（精修）越来越精确的反映。对主峰颗粒，在某同一半径下从刚开始精修的时候到终极精修的各轮数据进行分析，看是否有小侧峰出现，观察侧峰的变化趋势。侧峰的颗粒也进行上述实验。在多组数据在不同傅里叶半径下精修重构，对比分析不同傅里叶半径下终极精修后的结果，主峰颗粒，精修傅里叶半径增加，峰值的位置向右平移并且精修次数越多。
[Abstract]:High resolution frozen electron microscopy (HREM) reconstruction of viruses requires a large number of (tens of thousands of particles) of frozen electron microscopy photographs, and the processing of these electron microscopic photographs by program takes a lot of time. In fact, some of the particles processed by the program are noise particles. These particles are included in the batch data processed by the program during the reconfiguration, and the increase in the number of particles is reflected in the exponential increase in the calculation time of the program. In the process of refinement, the phase residuals and the number of particles show a double Gao Si peak model. Obviously, for the reasons of applying statistics and reconstruction method, the phase residuals and particle number graphs belong to two Gao Si peaks, and these main peak particles and side peak particles belong to two kinds of particles. In this paper, the principle, method, data processing flow and algorithm of three dimensional reconstruction of icosahedron virus are described in detail. The mixed Gao Si model of the number of phase residuals is obtained by analyzing the changing characteristics of the processed particles in the process of data processing, and the capsid structure of the adenovirus Ad5F35 is reconstructed, which reveals the conserved binding of fiber penton base. The interaction between fibers and receptors is well understood. The main contents are as follows: we reconstruct the three-dimensional structure of Ad5F35 capsid and show that the penton base binding of adenovirus fibers is conserved. By comparing the fiber structure of the Ad5F35 density map with the fiber structure of the virtual homologous Ad35 model composed of c terminal knob and shaft region, we confirm that the c terminal part of the tail (residual 22 / 43) is part of the length of shaft. It is located at the trunk bottom of the fiber shaft. In addition, based on our Ad5F35 structure, that is, the interaction model between CD46 and integrin receptor and Ad5F35 capsid, it is suggested that the Ads of short fiber may be able to bind integrin and CD46. at the same time. The relationship between the distance between two peaks and the resolution of virus structure in mixed Gao Si model is studied by processing several sets of virus data published in core journals of international related fields. Using multiple sets of data at different Fourier radii, the results of each round refinement at the same radius are compared and analyzed: for the main peak particles, the more refined the number of refinements in the same Fourier radius, the constant the position of the peak value. However, the whole peak particle is more and more concentrated near the peak value, and the distribution probability of the particle is more and more close to the peak value with the increase of refinement times, which should be more and more accurate reflection of measurement (refinement). The data of each round of the main peak particle from the beginning of finishing to the final refinement at the same radius are analyzed to see if there is a small side peak and observe the change trend of the side peak. The above experiments were also carried out on the side peak particles. After several sets of data are refined and reconstructed under different Fourier radii, the results of the final refinement under different Fourier radii are compared and analyzed. The main peak particles, the refined Fourier radius are increased, the peak position is shifted to the right and the number of refinements is increased.
【学位授予单位】：湘潭大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R373
本文编号：2274264
[Abstract]:High resolution frozen electron microscopy (HREM) reconstruction of viruses requires a large number of (tens of thousands of particles) of frozen electron microscopy photographs, and the processing of these electron microscopic photographs by program takes a lot of time. In fact, some of the particles processed by the program are noise particles. These particles are included in the batch data processed by the program during the reconfiguration, and the increase in the number of particles is reflected in the exponential increase in the calculation time of the program. In the process of refinement, the phase residuals and the number of particles show a double Gao Si peak model. Obviously, for the reasons of applying statistics and reconstruction method, the phase residuals and particle number graphs belong to two Gao Si peaks, and these main peak particles and side peak particles belong to two kinds of particles. In this paper, the principle, method, data processing flow and algorithm of three dimensional reconstruction of icosahedron virus are described in detail. The mixed Gao Si model of the number of phase residuals is obtained by analyzing the changing characteristics of the processed particles in the process of data processing, and the capsid structure of the adenovirus Ad5F35 is reconstructed, which reveals the conserved binding of fiber penton base. The interaction between fibers and receptors is well understood. The main contents are as follows: we reconstruct the three-dimensional structure of Ad5F35 capsid and show that the penton base binding of adenovirus fibers is conserved. By comparing the fiber structure of the Ad5F35 density map with the fiber structure of the virtual homologous Ad35 model composed of c terminal knob and shaft region, we confirm that the c terminal part of the tail (residual 22 / 43) is part of the length of shaft. It is located at the trunk bottom of the fiber shaft. In addition, based on our Ad5F35 structure, that is, the interaction model between CD46 and integrin receptor and Ad5F35 capsid, it is suggested that the Ads of short fiber may be able to bind integrin and CD46. at the same time. The relationship between the distance between two peaks and the resolution of virus structure in mixed Gao Si model is studied by processing several sets of virus data published in core journals of international related fields. Using multiple sets of data at different Fourier radii, the results of each round refinement at the same radius are compared and analyzed: for the main peak particles, the more refined the number of refinements in the same Fourier radius, the constant the position of the peak value. However, the whole peak particle is more and more concentrated near the peak value, and the distribution probability of the particle is more and more close to the peak value with the increase of refinement times, which should be more and more accurate reflection of measurement (refinement). The data of each round of the main peak particle from the beginning of finishing to the final refinement at the same radius are analyzed to see if there is a small side peak and observe the change trend of the side peak. The above experiments were also carried out on the side peak particles. After several sets of data are refined and reconstructed under different Fourier radii, the results of the final refinement under different Fourier radii are compared and analyzed. The main peak particles, the refined Fourier radius are increased, the peak position is shifted to the right and the number of refinements is increased.
【学位授予单位】：湘潭大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R373
【参考文献】
相关期刊论文 前1条
1 张运楚;李贻斌;张建滨;;高斯混合背景模型的方差估计研究[J];计算机工程与应用;2012年04期
本文编号：2274264
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