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dc.contributor.advisorGoryanin, Igoren
dc.contributor.advisorMa, Hongwuen
dc.contributor.authorKalapanulak, Saowalaken
dc.date.accessioned2010-10-12T15:16:52Z
dc.date.available2010-10-12T15:16:52Z
dc.date.issued2009
dc.identifier.urihttp://hdl.handle.net/1842/3925
dc.description.abstractMycobacterium tuberculosis (Mtb), a pathogenic bacterium, is the causative agent in the vast majority of human tuberculosis (TB) cases. Nearly one-third of the world’s population has been affected by TB and annually two million deaths result from the disease. Because of the high cost of medication for a long term treatment with multiple drugs and the increase of multidrug-resistant Mtb strains, faster-acting drugs and more effective vaccines are urgently demanded. Several metabolic pathways of Mtb are attractive for identifying novel drug targets against TB. Hence, a high quality genome-scale metabolic network of Mtb (HQMtb) was reconstructed to investigate its whole metabolism and explore for new drug targets. The HQMtb metabolic network was constructed using an unbiased approach by extracting gene annotation information from various databases and consolidating the data with information from literature. The HQMtb consists of 686 genes, 607 intracellular reactions, 734 metabolites and 471 E.C. numbers, 27 of which are incomplete. The HQMtb was compared with two recently published Mtb metabolic models, GSMN-TB by Beste et al. and iNJ661 model by Jamshidi and Palsson. Due to the different reconstruction methods used, the three models have different characteristics. The 68 new genes and 80 new E.C. numbers were found only in the HQMtb and resulting in approximately 52 new metabolic reactions located in various metabolic pathways, for example biosynthesis of steroid, fatty acid metabolism, and TCA cycle. Through a comparison of HQMtb with a previously published human metabolic network (EHMN) in terms of protein signatures, 42 Mtb metabolic genes were proposed as new drug targets based on two criteria: (a) their protein functional sites do not match with any human protein functional sites; (b) they are essential genes. Interestingly, 13 of them are found in a list of current validated drug targets. Among all proposed drug targets, Rv0189c, Rv3001c and Rv3607c are of interest to be tested in the laboratory because they were also proposed as drug target candidates from two research groups using different methods.en
dc.language.isoen
dc.publisherThe University of Edinburghen
dc.relation.hasversionThis work is currently transformed to a manuscript for submitting to BMC Bioinformatics in 2010 with the supplementary data about a complete list of included reactions in the HQMtb, a complete list of metabolites, and a list of references of particular reactions in the HQMtb as a text file.en
dc.subjectMycobacterium tuberculosisen
dc.subjecthigh quality genome-scale metabolic network of Mtben
dc.subjectHQMtb metabolic networken
dc.subjectEHMNen
dc.subjectdrug targetsen
dc.titleHigh quality genome-scale metabolic network reconstruction of mycobacterium tuberculosis and comparison with human metabolic network: application for drug targets identificationen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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