Genome-wide Studies of Mycolic Acid Bacteria: Computational Identification and Analysis of a Minimal Genome

Handle URI:
http://hdl.handle.net/10754/262832
Title:
Genome-wide Studies of Mycolic Acid Bacteria: Computational Identification and Analysis of a Minimal Genome
Authors:
Kamanu, Frederick Kinyua
Abstract:
The mycolic acid bacteria are a distinct suprageneric group of asporogenous Grampositive, high GC-content bacteria, distinguished by the presence of mycolic acids in their cell envelope. They exhibit great diversity in their cell and morphology; although primarily non-pathogens, this group contains three major pathogens Mycobacterium leprae, Mycobacterium tuberculosis complex, and Corynebacterium diphtheria. Although the mycolic acid bacteria are a clearly defined group of bacteria, the taxonomic relationships between its constituent genera and species are less well defined. Two approaches were tested for their suitability in describing the taxonomy of the group. First, a Multilocus Sequence Typing (MLST) experiment was assessed and found to be superior to monophyletic (16S small ribosomal subunit) in delineating a total of 52 mycolic acid bacterial species. Phylogenetic inference was performed using the neighbor-joining method. To further refine phylogenetic analysis and to take advantage of the widespread availability of bacterial genome data, a computational framework that simulates DNA-DNA hybridisation was developed and validated using multiscale bootstrap resampling. The tool classifies microbial genomes based on whole genome DNA, and was deployed as a web-application using PHP and Javascript. It is accessible online at http://cbrc.kaust.edu.sa/dna_hybridization/ A third study was a computational and statistical methods in the identification and analysis of a putative minimal mycolic acid bacterial genome so as to better understand (1) the genomic requirements to encode a mycolic acid bacterial cell and (2) the role and type of genes and genetic elements that lead to the massive increase in genome size in environmental mycolic acid bacteria. Using a reciprocal comparison approach, a total of 690 orthologous gene clusters forming a putative minimal genome were identified across 24 mycolic acid bacterial species. In order to identify new potential drug candidates against the pathogenic mycolic acid bacteria, a drug target analysis of the protein-coding genes, that are conserved across 15 pathogens, identified a total of 175 potential broad spectrum drug candidates. The activity of the predicted targets can be modified by a total of 306 chemical compounds, 34 of which have been approved by the Food and Drug Administration (FDA), for human treatment.
Advisors:
Bajic, Vladimir B. ( 0000-0001-5435-4750 ) ; Archer, John A. C.
Committee Member:
Gao, Xin ( 0000-0002-7108-3574 ) ; Gehring, Christoph A ( 0000-0003-4355-4591 ) ; Magistretti, Pierre; Narasimhan, Kothandaraman
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Program:
Bioscience
Issue Date:
Dec-2012
Type:
Dissertation
Appears in Collections:
Bioscience Program; Dissertations; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.advisorBajic, Vladimir B.en
dc.contributor.advisorArcher, John A. C.en
dc.contributor.authorKamanu, Frederick Kinyuaen
dc.date.accessioned2012-12-16T13:20:07Z-
dc.date.available2012-12-16T13:20:07Z-
dc.date.issued2012-12en
dc.identifier.urihttp://hdl.handle.net/10754/262832en
dc.description.abstractThe mycolic acid bacteria are a distinct suprageneric group of asporogenous Grampositive, high GC-content bacteria, distinguished by the presence of mycolic acids in their cell envelope. They exhibit great diversity in their cell and morphology; although primarily non-pathogens, this group contains three major pathogens Mycobacterium leprae, Mycobacterium tuberculosis complex, and Corynebacterium diphtheria. Although the mycolic acid bacteria are a clearly defined group of bacteria, the taxonomic relationships between its constituent genera and species are less well defined. Two approaches were tested for their suitability in describing the taxonomy of the group. First, a Multilocus Sequence Typing (MLST) experiment was assessed and found to be superior to monophyletic (16S small ribosomal subunit) in delineating a total of 52 mycolic acid bacterial species. Phylogenetic inference was performed using the neighbor-joining method. To further refine phylogenetic analysis and to take advantage of the widespread availability of bacterial genome data, a computational framework that simulates DNA-DNA hybridisation was developed and validated using multiscale bootstrap resampling. The tool classifies microbial genomes based on whole genome DNA, and was deployed as a web-application using PHP and Javascript. It is accessible online at http://cbrc.kaust.edu.sa/dna_hybridization/ A third study was a computational and statistical methods in the identification and analysis of a putative minimal mycolic acid bacterial genome so as to better understand (1) the genomic requirements to encode a mycolic acid bacterial cell and (2) the role and type of genes and genetic elements that lead to the massive increase in genome size in environmental mycolic acid bacteria. Using a reciprocal comparison approach, a total of 690 orthologous gene clusters forming a putative minimal genome were identified across 24 mycolic acid bacterial species. In order to identify new potential drug candidates against the pathogenic mycolic acid bacteria, a drug target analysis of the protein-coding genes, that are conserved across 15 pathogens, identified a total of 175 potential broad spectrum drug candidates. The activity of the predicted targets can be modified by a total of 306 chemical compounds, 34 of which have been approved by the Food and Drug Administration (FDA), for human treatment.en
dc.language.isoenen
dc.subjectBioinformaticsen
dc.subjectPhylogenyen
dc.subjectMycolic Acid Bacteriaen
dc.subjectGenomicsen
dc.subjectSystematicsen
dc.titleGenome-wide Studies of Mycolic Acid Bacteria: Computational Identification and Analysis of a Minimal Genomeen
dc.typeDissertationen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
thesis.degree.grantorKing Abdullah University of Science and Technologyen_GB
dc.contributor.committeememberGao, Xinen
dc.contributor.committeememberGehring, Christoph Aen
dc.contributor.committeememberMagistretti, Pierreen
dc.contributor.committeememberNarasimhan, Kothandaramanen
thesis.degree.disciplineBioscienceen
thesis.degree.nameDoctor of Philosophyen
dc.person.id102012en
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