Computational methods applied to the genomes of the mycobacteria and trypanosomatids: of the assembly to the notation.
This dissertation deals with the development of new methods and computational tools with the following applications: improvement of the pipeline of the sequencing andbioinformatics technological platforms; sequences assembly; detection of repetitive sequences; comparative analysis and annotation of genomes. The majority of the tools wasapplied in the genome project of the Mycobacterium bovis strain BCG Moreau-RJ, which was sequenced, assembled and annotated in our laboratory. Results of this genome project, such as the development of tools for genetic identification and quality control, which can be used in the maintenance and production of the vaccine BCG Moreau-RJ have been included in a national and international patent deposit. This work also presents some complementary, yet independent systems designed for the analysis of genomes in general, which allow for a series of applications at the in silico ? in vitro interface. (1) ReRep (Read Repeat Finder) is a system that detects repetitive sequences in a genome survey sequencing data set (GSS), aiming at the characterization of repetitions and supporting the assembly of genomes. The tool was applied on a set of GSS covering 1.4 % of the genome of Leishmania braziliensis. (2) AnEnPi (Analogous Enzyme Pipeline), based on a dataset of enzymes for the annotation of metabolic pathways and detection of possible drug targets. The tool offers the possibility for comparison, generation and visualization of metabolic maps, applied to L. major and Trypanosoma cruzi. (3) Set of programs and tools applied to the assembly and the annotation of the genome of BCG Moreau-RJ: webpages of the project, including statistics of assembly and visualization of the mapping of reads against the Mycobacterium bovis genome;workflow for genome assembly; two programs - for the characterization of gaps (GFK "Gap- Find-Kill") and PCR "in silico? - for the finishing process of the assembly; a tool to annotate target genomes using a reference genome; methods and the program AceSNPFinder to find insertions, deletions, inversions, rearrangements, exchanges, duplications and polymorphisms to compare the genome of the BCG Moreau-RJ with others strains of BCG and M. tuberculosis, and comparison of genomes in general; (4) Implementation of the platforms:DNA Sequencing and Bioinformatics, both part of the PDTIS program (Programa de Desenvolvimento Tecnológico de Insumos para a Saúde).
Advisor:Celso da Cruz Carneiro Ribeiro; Wim Maurits Sylvain Degrave
School:Faculdades Oswaldo Cruz
Source Type:Master's Thesis
Keywords:Computational Biology Genome BCG Vaccine Case-Control Studies Bacterial Genomics BIOFISICA MOLECULAR
Date of Publication:02/28/2008