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生物网络模块化的计算方法及应用
其他题名Computational Methods and Applications of Modularity in Biological Networks
蒋兴鹏
学位类型工学博士
导师蒋田仔
2009-05-27
学位授予单位中国科学院研究生院
学位授予地点中国科学院自动化研究所
学位专业模式识别与智能系统
关键词生物网络 模块化 系统生物学 疾病表型 蛋白质交互网络 Biological Networks Modularity Systems Biology Disease Phenotype Protein-protein Interaction Network
摘要复杂生物网络的模块化研究对于理解复杂网络结构,以及各种生物网络的运行机制有着重要的意义,是当前系统生物学研究中的热点问题之一。本文针对这个问题从网络模块化的计算方法及其在具体生物网络中的应用两个角度进行了较为系统的研究,主要贡献如下: 1. 重叠层次的模块化方法研究:生物系统具有重叠的和层次的模块化结构,这两种结构是大部分生物网络的内在属性。有效地提取这两种结构,才能够更加真实的反映生物系统的本质,使得计算结果更有应用价值。本文提出了一种基于一致性聚类和非负矩阵分解的模块化方法,该方法能同时提取网络的模块化层次水平和重叠的模块化结构。 2. 人类遗传疾病表型网模块化结构的系统分析:相似的疾病常常是由功能相关的基因突变造成,因此相似的疾病表型在网络中应该也是以共模块的形式存在。利用表型相似性数据,本文构建了一个人类遗传疾病表型相似网络,验证了这种模块化结构的存在性,并且计算提取了重要的表型模块,发现这些表型模块和已知的人类疾病分类相符;基于以上结果,我们进一步调查了这种模块化和功能基因组学以及药物组学之间的关联。 3. 蛋白质交互网络的模块化结构及其生物意义分析:首先考察了酵母蛋白质交互网络,利用模块化所定义的网络节点角色、结合基因复制、单基因删除等信息来考察生物系统的遗传鲁棒性;然后分析了人类蛋白质交互网络的模块化结构,从结构模块内的蛋白功能相似度和表型相似度两个方面研究了人类蛋白质交互网络结构模块化的生物学意义,并考察了节点角色和基因的关键性、多效性等基因功能属性之间的关系。 总之,本文围绕模块化的方法学和实际应用展开,提出了一种提取生物网络层次和重叠模块化结构的计算方法,并在模拟数据和真实数据上分别验证了该方法的有效性;系统分析了人类遗传疾病表型网络的模块化性质,试图从表型组层次发现模块化与基因功能之间的关系;进一步考察了酵母和人类蛋白质交互网络的模块化结构与进化、疾病、基因功能之间的关联。
其他摘要The study of modularity in complex biological network is important for understanding the structure of complex networks and the mechanism of biological systems. It is one of the essential aspects of studies in systems biology. In this thesis, I studied systematically this problem in the following two ways: the computational methods of network modularity and the analysis of modularity in specific biological networks. The main contributions of this thesis are as follows: 1. Computational method for extracting hierarchical and overlapping modularity of biological networks: Biological networks often have both hierarchical and overlapping modularity organizations. These aspects are the intrinsic properties of biological networks. Thus a computational method of modularity is said to be effective only when it can detect both structures. The results like this can reflect the fact of biological systems and be more practical and predictive. We proposed a new framework to solve the problems based on consensus clustering and non-negative factorization. The method extracted the correct level of hierarchy and reflected the overlapping between modules. 2. Systematical analysis of modularity in the disease phenotypic network: Similar disease phenotypes are begotten by the modular nature of gene network, thus we suppose that all human disease phenotypes also appear in a modular style. We gave a network representation of phenotypes using the dataset of phenotypic similarity. We investigated the modularity of the disease phenotype network. We computationally extracted significant phenotype modules and found that the modularity is correlated well with the physiological classification of human diseases. We also found relationships between the modularity and function genomics as well as drug discovery 3. The modularity in protein-protein interaction networks and the biological implications: Firstly we investigated the interactome of yeast. We used quantities introduced by the modularity to describe network properties of genes and to investigate the correlations between duplicate genes and genetic robustness in yeast. Secondly, we confirmed the existence of the structural modularity in human protein-protein interaction network and evaluated the biological significance of the modularity from the similarity of gene’s functions and that of human disease phenotypes. At last, we defined the roles of proteins based on the modularity and investigated the relationship between the rol...
馆藏号XWLW1313
其他标识符200518014628051
语种中文
文献类型学位论文
条目标识符http://ir.ia.ac.cn/handle/173211/6168
专题毕业生_博士学位论文
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蒋兴鹏. 生物网络模块化的计算方法及应用[D]. 中国科学院自动化研究所. 中国科学院研究生院,2009.
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