基于生物信息學的腸出血性大腸埃希菌O157:H7的致病機制及診斷靶標的研究
本文選題:腸出血性大腸埃希菌O157 + H7。 參考:《吉林大學》2010年博士論文
【摘要】: 腸出血性大腸埃希菌O157:H7(Enterohemorrhagic Escherichia coli O157:H7,EHEC O157:H7)是重要的食源性致病菌,低劑量感染即可威脅生命,發(fā)病率和死亡率有不斷上升的趨勢,近年來美國和日本等發(fā)達國家有不同規(guī)模的爆發(fā)流行,我國江蘇、安徽省曾于1999年爆發(fā)流行EHEC O157:H7感染性腹瀉。對此病原菌致病機制及診斷靶標的研究將對提高腸道傳染病的防治及腸道病原菌診斷水平具有重要的理論和實踐意義。隨著大規(guī)模的微生物基因組計劃的實施和取得的驕人的成績,極大地豐富了生物信息學的內容,為人類提供了呈指數級增長的生物學數據,推動了微生物信息學的建立和發(fā)展,為探索微生物結構基因組和功能基因組之間的內在聯系提供了可分析的基因調控網絡,為揭示基因如何行使其職能控制生命現象,發(fā)現新的生物學規(guī)律奠定了基礎。面對不斷豐富的微生物基因組資源,如何更好的挖掘海量遺傳數據中所隱藏的信息,揭示基因位置、結構與功能、表達調控方式及致病機理之間的關系等,已成為比測序本身更有意義的工作。本研究應用生物信息學方法建立的“基因組條形碼”注釋系統(tǒng)研究平臺及比較基因組學分析,高通量注釋細菌基因組海量的序列數據,將生物信息學方法與分子生物學實驗科學相融合,高通量地篩選及注釋了EHEC O157:H7的毒力島,預測及初步驗證了EHEC O157:H7診斷靶標,全基因組掃描及分析EHEC O157:H7轉座子插入序列及其功能,體現了將生物信息學方法與分子生物學實驗科學相融合的研究特色,從而推動細菌基因測序結果向高通量的基因組注釋及生物科學證實的綜合研究新途徑的發(fā)展。
[Abstract]:Escherichia coli O157: H7 (Enterohemorrhagic Escherichia coli O157: H7) is an important foodborne pathogenic bacterium. Low dose infection can threaten life, and morbidity and mortality have been increasing. In recent years, there have been outbreaks of epidemics on different scales in developed countries such as the United States and Japan. EHEC O 157: h 7 infectious diarrhea occurred in Jiangsu and Anhui provinces in 1999. The study on the pathogenic mechanism and diagnostic target of this pathogen will be of great theoretical and practical significance in improving the prevention and treatment of intestinal infectious diseases and the level of diagnosis of intestinal pathogens. With the implementation of the large-scale microbial genome project and the remarkable achievements, it has greatly enriched the content of bioinformatics, provided the biological data with exponential growth, and promoted the establishment and development of microbial informatics. It provides an analytical gene regulatory network for exploring the internal relationship between microbial structural genomes and functional genomes and lays a foundation for revealing how genes exercise their functions to control life phenomena and to discover new biological laws. In the face of the abundant microbial genome resources, how to better excavate the hidden information in the massive genetic data, reveal the position, structure and function of the gene, express the regulation mode and the relationship between the pathogenic mechanism and so on. Has become more meaningful than sequencing itself. In this study, the "genome bar code" annotation system developed by bioinformatics method and comparative genomics analysis were used to annotate the mass sequence data of bacterial genome in high throughput. The virulence islands of EHEC O157: H7 were screened and annotated in high throughput by combining bioinformatics with molecular biology experimental science. The EHEC O157: H7 diagnostic target was predicted and preliminarily verified. The whole genome scanning and analysis of EHEC O157: H7 transposon insert sequence and its function were carried out. The research features of combining bioinformatics with molecular biology experimental science are embodied, thus promoting the development of bacterial gene sequencing results to high-throughput genome annotation and comprehensive research approaches confirmed by biological science.
【學位授予單位】:吉林大學
【學位級別】:博士
【學位授予年份】:2010
【分類號】:R378.21
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