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基于局部和系统的生物网络研究及其应用
其他题名Analyses and applications of biological Network based on local and global characteristics
赵慧智
2009-05-27
学位类型工学博士
中文摘要随着生物技术的发展,生物数据以爆炸的速度增长。如何利用现有的庞大的生物数据来解决生物学的问题,是生物信息学研究的一个重要目的。随着人类全基因组测序计划的顺利完成,基因组、蛋白质组、交互作用组等大数量的数据逐渐增加,基于单个基因或蛋白的分析方法已经无法满足数据和问题的需求,系统层次的网络分析方法开始迅速发展。本文我们充分了利用了生物网络在集成不同来源数据的优势,通过对基因集合和全局网络系统的分析,来解决我们所关注的生物问题。 microRNA(miRNA)是在各种生命过程中具有重要意义的非编码RNA,了解它的功能和特性有重要意义。我们通过研究miRNA的重组率与其组织特异性、表达水平高低、疾病相关个数的关系,发现作为序列特征的重组率与这些外部特征都有显著的相关。由于基于单个miRNA的差异表达分析具有一定的局限性,我们在miRNA集合(miRNA set)水平上寻找精神分裂症与正常人的差异表达。进一步,我们构建了miRNA共表达网络和基因共表达网络,结合miRNA与基因的调控关系,通过网路比对找到了和精神分裂症相关的miRNA模块。 从基因表达数据来反推基因交互作用是网络分析的一个重要方面。我们用微分方程的方法来反推在脑内表达的基因相互作用网络,并用来分析与阿尔茨海默症发生发展相关的基因,同时结合蛋白交互作用网络,寻找到更多的阿尔茨海默症相关的基因,得到与阿尔茨海默症的发病机制相一致的相关的功能通路―神经细胞通路和Ca2+<上标!>通路。 新陈代谢网络是一个结合了多种数据的综合网络,我们利用流平衡分析和模拟基因敲除的方法,得到了模式生物的重要基因和非重要基因。我们把这些基因映射到人类基因组上,比较这两类基因的重组率差别,我们发现重要基因与非重要基因相比重组率较低,相对比较保守。 综上,我们从局部和系统的水平分析了不同类型的生物网络,来解决我们关心的生物问题。结果表明,从网络的层次来分析生物数据,可以充分利用大量的异质生物数据的优势来解决生物问题。
英文摘要As the development of the biological technique, mountains of biological data appeared. It is an important goal to find out the answers to the concerning questions from the biological data. As the success of the whole genome sequencing, genome, protome, interactome become the hotspots of bioinformatics. The one to one analyses are not adequate for the data scale and biological questions. Methods of local and global analysis of network appeared. We studied different biological network from set analysis (local characteristic of network) and global network view and solved biological questions. microRNAs (miRNAs) are non-coding RNAs that play key roles in almost every critical process. It is important to understand their functions and characteristics. We studied the associations between recombination rates of miRNAs and their tissue specificity, expression levels and related disease numbers, and found out that they were all significantly related. We also used miRNA set enrichment analysis to found the differentiation expressed miRNAs in schizophrenia. We then reconstructed miRNA co-expression network and gene co-expression network, compared the two networks by their toopological characteristics and the miRNA-gene regulation, and found out a miRNA module that is associated with schizophrenia. It is an important method to reconstruct gene interaction network from gene expression profiles and carried on further studies based on this network. We reconstructed a brain-related gene interaction network from different gene expression profiles, and found the differentiated genes in the incipient, moderate, severe stages of Alzheimer's disease respectively. We also combined protein-protein interaction network to improve the accurary, and got two differentiated biological function clusters that consistented with the processes of the Alzheimer’s disease, neuron functions and Ca2+<上标!> homeostasis changes. Metabolic network is a network that includes the relations of genes, proteins and reactions. We used flux balance anlaysis and in-silico gene deletion in the metabolic networks in model organisms, and grouped the genes into important genes and non-important ones. We mapped these genes to human genome, and compared the recombination rates of the orthologous genes of two groups. We found out that the important genes had lower recombination rates than the non-important ones and more conservative. As a whole, we analyzed the local and the global characteristics ...
关键词基因芯片表达数据 Mirna 生物网络 重组率 疾病 Network Gene Expression Mirna Recombinatioin Rate Disease
语种中文
文献类型学位论文
条目标识符http://ir.ia.ac.cn/handle/173211/6169
专题毕业生_博士学位论文
推荐引用方式
GB/T 7714
赵慧智. 基于局部和系统的生物网络研究及其应用[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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