Browsing by Author "Seoighe, Cathal"

Now showing 1 - 4 of 4
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    Analyses of sequence divergence using completely sequenced genomes
    (University of the Western Cape, 2003) Nembaware, Victoria P.; Seoighe, Cathal
    Using the complete genome, Saccharomyces cerevisiae, which duplicated after its speciation fuom Kluyveromyces lactics, a dataset of 119 putative S. cerevisiae - K. lactis ortholog-pairs was constructed. S. cerevisiae paralogous pairs that are likely to have duplicated during the whole genome duplication of S. cerevisiae were obtained and the approach taken in our previous work (Nembaware et al., 20OZ), was repeated to test whether the presence of a paralogue in S. cerevisiae had an effect on the rate of sequence divergence of the 119 pairs of orthologous genes. We found, however, that substitutions at synonymous sites had reached saturation and this prevented us from being able to repeat the previous finding with S. cerevistae and K. lactis . From this study a publicly available web-server (http://hamlyn.sanbi.ac.zal-victoria) that automates the calculation of Ka:Ks values given a pairs homologous CDS sequences is presented.
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    Detection of positive selection resulting from Nevirapine treatment in longitudinal HIV-1 reverse transcriptase sequences
    (University of the Western Cape, 2006) Ketwaroo, Bibi Farahnaz K.; Hide, Winston; Seoighe, Cathal; Scheffle, Konrad; South African National Bioinformatics Institute (SANBI); Faculty of Science
    Nevirapine (NVP) is a cheap anti-retroviral drug used in poor countries worldwide, administered to pregnant women at the onset of labour to inhibit HIV enzyme reverse transcriptase. Viruses which may get transmitted to newborns are deficient in this enzyme, and HIV-1 infection cannot be established, thereby preventing mother to child transmission (MTCT). In some cases, babies get infected and positive selection for viruses resistant to nevirapine may be inferred. Positive selection can be inferred from sequence data, when the rate of nonsynonymous substitutions is significantly greater than the rate of synonymous substitutions. Unfortunately, it is found that available positive selection methods should not be used to analyse before- and after- NVP treatment sequence pairs associated with MTCT. Methods which use phylogenetic trees to infer positive selection trace synonymous and nonsynonymous substitutions further back in time than the short time duration during which selection for NVP occurred. The other group of methods for inferring positive selection, the pairwise methods, do not have appreciable power, because they average susbtituion rates over all codons in a sequence pair and not just at single codons. We introduce a simple counting method which we call the Pairwise Homologous Codons (PHoCs) method with which we have inferred positive selection resulting from NVP treatment in longitudinal HIV-1 reverse transcriptase sequences. The PHoCs method estimates rates of substitutions between before- and after- NVP treatment codons, using a simple pairwise method.
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    FRAGS: Estimation of coding sequence substitution rates from fragmentary data
    (BMC, 2004) Swart, Estienne C; Hide, Winston A; Seoighe, Cathal
    Rates of substitution in protein-coding sequences can provide important insights into evolutionary processes that are of biomedical and theoretical interest. Increased availability of coding sequence data has enabled researchers to estimate more accurately the coding sequence divergence of pairs of organisms. However the use of different data sources, alignment protocols and methods to estimate substitution rates leads to widely varying estimates of key parameters that define the coding sequence divergence of orthologous genes. Although complete genome sequence data are not available for all organisms, fragmentary sequence data can provide accurate estimates of substitution rates provided that an appropriate and consistent methodology is used and that differences in the estimates obtainable from different data sources are taken into account.
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    HIV subtype C diversity: analysis of the relationship of sequence diversity to proposed epitope locations
    (University of the Western Cape, 2002) Ernstoff, Elana Ann; Hide, Winston; Seoighe, Cathal; South African National Bioinformatics Institute (SANBI); Faculty of Science
    Southern Africa is facing one of the most serious HIV epidemics. This project contributes to the HIVNET, Network for Prevention Trials cohort for vaccine development. HIVÂ’s biology and rapid mutation rate have made vaccine design difficult. We examined HIV-1 subtype C diversity and how it relates to CTL epitope location along viral gag sequences. We found a negative correlation between codon sites under positive selection and epitope regions; suggesting epitope regions are evolutionarily conserved. It is possible that epitopes exist in non-conserved regions, yet fail to be detected due to the reference strain diverging from the circulating viral population. To test if CTL clustering is an artifact of the reference strain, we calculated differences between the gag codons and the reference strain. We found a weak negative correlation, suggesting epitopes in less conserved regions maybe evading detection. Locating conserved and optimal epitopes that can be recognized by CTLs is essential for the design of vaccine reagents.