The Viral Diversity and Bioinformatics Core will support the objectives of all four CAPRISA projects by undertaking PCR analysis on partial and full-length genomes, the heteroduplex mobility and tracking assays for defining genetic variability, sequence analysis, drug resistance genotyping and establishing integrated databases with sequence, clinical and immunological information. The functions of the core have been distributed between three centers to avoid duplication and optimally utilize existing strengths and expertise. The three centers involved complement each other by providing distinct services and unique expertise: The sequencing, quality control of sequences, heteroduplex mobility assays and heteroduplex tracking assays will be conducted at the University of Cape Town by the Core Leader, Carolyn Williamson. Resistance genotyping, OLA (Oligonucleotide Ligation Assay) and SNP (Single Nucleotide Polymorphisms) assays will be performed at the University of Natal by core co-leader, Sharon Cassol. The phylogenetic analysis, computational training and support, as well as the bioinformatics database will be located at the South African National Bioinformatics Institute, University of Western Cape by core co-leader, Winston Hide. The bioinformatics component of this core will have a computational biology section which will be responsible for the development of new tools needed for the analysis of evolution of viral populations. The core will be linked via a password-protected website that provides information from a back-end database on project progress at each site, such as sample tracking and analytical tools and the progress of pipelined analyses. The web interface will serve as a medium for communication between sites and also as a directed information portal to support the activities at each site. The CAPRISA investigators involved in this core will also participate in the training program as outlined in the administration core. In this regard, the core will work in collaboration with three US laboratories based at the University of Washington (James Mullins) on advanced computational analysis, the Henry Jackson Foundation (Francine McCutchan) on whole genome sequencing and the University of North Carolina (Ronald Swanstrom) on development of methodologies for tracking sequence changes over time. This core will contribute to all four CAPRISA projects. It will be involved in sequencing and tracking genetic changes in HIV over time in the acute seroconversion project, genetic characterisation of breakthrough infections in the study of highly exposed persistently seronegative individuals, subtyping of circulating HIV-1 strains in the evolving HIV epidemic project, and screening HIV reverse transcriptase for drug resistance mutations in the antiretroviral therapy project. In addition, the database will integrate sequence and immunological data with clinical data for analysis of the relationship between viral isolates, selective pressures and set point in the acute seroconversion project.
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