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Comparative genomics of microbial genomes and development of a comprehensive chlamydiae genome database.
München, Technische Universität München, Fakultät Wissenschaftszentrum Weihenstephan, Diss., 2011, 206 S.
It is a long time since bacteria are investigated as they play important roles in biotechnology, disease management, biodefense and chronic diseases of humans. Nevertheless it was only feasible to analyze a small number of model organisms as Escherichia coli or Bacillus subtilis in depth in the laboratory as this research is time consuming and expensive. The knowledge gained in model organisms is transferred to novel organisms if signicant sequence homology between the genetic elements can be detected. Therefore, with the availability of the sequences of many prokaryotic genomes due to novel sequencing technologies, the impact of comparative genomics on the microbiological research has grown over the last 15 years. Bioinformatics provides means to handle and compare the data and by that generates hypotheses that can be checked in experiments in the laboratory. As many bioinformatics analyses can only be conducted with considerable eort for every novel genome sequence by bioinformaticians, the automation of bioinformatics analyses is as essential as the preparation of data for non-bioinformaticians working in the laboratories. Therefore the aims of this work were the automation and improvement of bioinformatics analysis methods for prokaryotic genomes, and to make the capability of comparative genomics easily available for non-bioinformaticians. This work describes the results of collaborations with dierent scientists working on prokaryotes in the laboratory. Bioinformatics standard analyses like the search for best BLAST hits have been applied to the genome sequences of the organisms and comparative genomics has been especially successful adressing various biological issues. An example important for all prokaryotic genome projects is the improvement of the gene prediction in prokaryotic genomes. Dierent conicts can occur as gene nders can predict dierent possible gene starts, and gene models can overlap. The automatic gene prediction pipeline ConsPred has been set up, that is able to resolve such conicts in unambiguous cases by the integration of knowledge about conserved sequences in other organisms. This minimizes the manual eort necessary for the gene prediction in prokaryotic genomes. An example for a detailed description of a prokaryotic genome and thereby the characterization of a prokaryote is the comprehensive analysis of the genome of the Gram-negative opportunistic foodborne pathogen Cronobacter turicensis LMG 23827, that is known as rare but important cause of live-threatening neonatal infections. Several features could be identied that suggest an originally plant-associated lifestyle of Cronobacter spp. 44 potential horizontally transferred genes closely related to sequences in non-enterobacterial often plant-associated bacteria could be detected. Additionally pathways typical for plant-associated organisms could be identied. Supplementary it is already known, that Cronobacter spp. are generally capable to utilize a wide variety of compounds as a sole carbon source. Some of them such as L-arabinose, D-xylose, D-cellobiose and palatinose are known to be produced and potentially exudated by plants. The presence of a Type IV and a Type VI secretion system as well as the presence of an array of putative eukaryotic protein domains give a possible explanation for the potential of transferring DNA and eector proteins from the bacterial to host cells as a mechanism of interaction with a eukaryotic host. An example for prokaryotes, in which comparative genomics plays an very specic role, are Chlamydiae, obligate intracellular bacteria and major pathogens of humans. The ability to specically inactivate and reactivate single genes is central to show gene functions, e.g. in knockout experiments. As it is not possible to genetically manipulate Chlamydiae bioinformatics and comparative genomics play an essential role in the research on Chlamydiae. In order to allow non-bioinformaticians to work with state-of-the-art bioinformatics methods and the available data of Chlamydiae, ChlamydiaeDB, a novel multi-genome database, was specically developed for members of the phylum Chlamydiae. It facilitates the interactive analysis of all available chlamydial genomes by comprehensively integrating heterogeneous information from diverse sources in one place, structuring genes in clusters of orthologs, providing unique tools for comparative and functional genomics, and manual annotation possibilities. The available data comprises automatic annotations, as well as data from experiments, e.g. SNP and transcript data. A Chlamydiae specic textmining procedure has been developed. The possibility to retrieve all information about a group of proteins, feature enrichment in a group of proteins as well as a graphical KEGG pathway comparison make the resource a valuable tool for scientists working with genomic data of Chlamydiae. ChlamydiaeDB is easily maintainable and extensible (http://www.chlamydiaedb.org).
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Publication type Other: Thesis
Thesis type Doctoral thesis
Keywords Chlamydiae; Bioinformatics; Bioinformatische Analysemethoden; prokaryotische Genome;
University Technische Universität München
University place München
Faculty Fakultät Wissenschaftszentrum Weihenstephan