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1.  Advanced significance analysis of microarray data based on weighted resampling: a comparative study and application to gene deletions in Mycobacterium bovis 
Bioinformatics (Oxford, England)  2004;20(3):357-363.
Motivation
When analyzing microarray data, non-biological variation introduces uncertainty in the analysis and interpretation. In this paper we focus on the validation of significant differences in gene expression levels, or normalized channel intensity levels with respect to different experimental conditions and with replicated measurements. A myriad of methods have been proposed to study differences in gene expression levels and to assign significance values as a measure of confidence. In this paper we compare several methods, including SAM, regularized t-test, mixture modeling, Wilk’s lambda score and variance stabilization. From this comparison we developed a weighted resampling approach and applied it to gene deletions in Mycobacterium bovis.
Results
We discuss the assumptions, model structure, computational complexity and applicability to microarray data. The results of our study justified the theoretical basis of the weighted resampling approach, which clearly outperforms the others.
Availability
Algorithms were implemented using the statistical programming language R and available on the author’s web-page.
doi:10.1093/bioinformatics/btg417
PMCID: PMC3128991  PMID: 14960462
2.  Molecular Epidemiology of Disease Due to Mycobacterium bovis in Humans in the United Kingdom 
Journal of Clinical Microbiology  2004;42(1):431-434.
Mycobacterium bovis is the causative agent of bovine tuberculosis, with a wide host range. Fifty human M. bovis isolates were typed using spoligotyping and variable number tandem repeats (VNTR). Fifteen of these spoligotypes have not yet been recorded in cattle. The predominant spoligotype in humans and cattle was subdivided by VNTR.
doi:10.1128/JCM.42.1.431-434.2004
PMCID: PMC321667  PMID: 14715798
4.  Genomic Analysis of Mycobacterium tuberculosis Complex Strains Used for Production of Purified Protein Derivative 
Journal of Clinical Microbiology  2003;41(8):3929-3932.
The genomes of the tuberculin production strains Mycobacterium bovis AN5 and Mycobacterium tuberculosis DT were compared to genome-sequenced tubercle bacilli by using DNA microarrays. Neither the AN5 nor DT strain suffered extensive gene deletions during in vitro passage. This suggests that bovine tuberculin made from M. bovis AN5 is suitable to detect infection with presently prevalent M. bovis strains.
doi:10.1128/JCM.41.8.3929-3932.2003
PMCID: PMC179793  PMID: 12904421
5.  Molecular Typing of Mycobacterium bovis Isolates from Cameroon 
Journal of Clinical Microbiology  2001;39(1):222-227.
In order to gain a better understanding of the molecular epidemiology of Mycobacterium bovis isolates in Cameroon, 75 isolates of M. bovis collected in three provinces of northern Cameroon were studied by spoligotyping. For 65 of these isolates, typing was also carried out by pulsed-field gel electrophoresis (PFGE) with DraI, and 18 of the isolates were also typed by restriction fragment length polymorphism (RFLP) analysis with probe IS6110-RHS. Molecular typing of the isolates by these techniques revealed a high degree of homogeneity, with 10 spoligotypes for 75 isolates, four PFGE profiles for 65 isolates, and three RFLP types for 18 isolates. Some types were present in the three different provinces, while some were confined to one or two areas. These results suggest that geographical mapping of M. bovis strains could be helpful for the control of bovine tuberculosis at the regional level. An interesting feature of all the spoligotypes was the absence of spacer 30, suggesting a common origin for all of the Cameroon isolates tested; an evolutionary scenario for the isolates is discussed. In addition, a comparison of the three techniques showed that for M. bovis strain differentiation in Cameroon and in surrounding countries, spoligotyping would be a more discriminating and practical tool for molecular typing than the other two techniques used in this study.
doi:10.1128/JCM.39.1.222-227.2001
PMCID: PMC87706  PMID: 11136775

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