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The transciptomic landscape of HIV-TB
Includes abstract.
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| Main Author: | |
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Department of Medicine
2014
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| _version_ | 1867613224286814208 |
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| access_status_str | Open Access |
| author | Deffur, Armin |
| author2 | Mulder, Nicola |
| author_browse | Deffur, Armin Mulder, Nicola |
| author_facet | Mulder, Nicola Deffur, Armin |
| author_sort | Deffur, Armin |
| collection | Thesis |
| description | Includes abstract. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/3377 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:32:44.899Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2014 |
| publishDateRange | 2014 |
| publishDateSort | 2014 |
| publisher | Department of Medicine |
| publisherStr | Department of Medicine |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/3377 The transciptomic landscape of HIV-TB Deffur, Armin Mulder, Nicola Wilkinson, Robert J Mayosi, Bongani M Medicine Includes abstract. Includes bibliographical references. The thesis consists of four main parts. In Part 1 of this thesis I provide a broad overview of HIVTB with an emphasis on systems approaches followed by an overview of a systems-level study aiming at addressing hypotheses relating to transcriptional differences in active tuberculosis and HIV-1 infection, measured in blood and the site of disease in tuberculous pericarditis. The final chapter in this part describes the methods used to generate and analyse the systems-level data, with emphasis on microarray data generation and analysis. Part 2 first presents analysis of transcriptional data generated by RT-PCR at the site of disease compared to blood in study subjects with tuberculous pericarditis, with results showing clear evidence of transcriptional differences between compartments. A Technical Results chapter then provides an overview of the microarray data, and an analytic paradigm based on sample embedding in high-dimensional phenotype space is developed. I then assess the overall quality of the dataset and exclude large-scale systematic bias, while comparison of the IMPI-MA data to exiting TBtranscriptomic data shows a close match. Part 2 concludes with a description of a comprehensive analytic framework developed for the IMPI-MA data. Part 3 presents the results of the analytic pipeline as applied to the transcriptional response in blood to active tuberculosis in an HIV-1 uninfected population. A signature of active tuberculosis is described, and deconvolution analysis finds significant NK cell activation in active tuberculosis. Cell-type specific differential expression identifies CD4 T cells, NK cells and neutrophils as the most likely contributors to the overall “signature” of active tuberculosis. Weighted gene co-expression network analysis reveals multiple modules, whose expression is shown to be differentially regulated based on disease category. Part 4 summarises the results of analysing contrasts in three main contexts: tuberculosis, HIV-1 infection and compartment. Two novel results are presented: Firstly, NK cells are shown to be functionally downregulated at the site of disease, suggesting a possible defence mechanism by M. tuberculosis, and secondly, large-scale metabolic pathway dysregulation at the site of disease, possibly favouring M. tuberculosis, is demonstrated. Part 5 concludes the thesis with a summary and outlines future work. 2014-07-29T09:03:07Z 2014-07-29T09:03:07Z 2013 Doctoral Thesis Doctoral Ph D http://hdl.handle.net/11427/3377 eng application/pdf Department of Medicine Faculty of Health Sciences University of Cape Town |
| spellingShingle | Medicine Deffur, Armin The transciptomic landscape of HIV-TB |
| thesis_degree_str | Doctoral |
| title | The transciptomic landscape of HIV-TB |
| title_full | The transciptomic landscape of HIV-TB |
| title_fullStr | The transciptomic landscape of HIV-TB |
| title_full_unstemmed | The transciptomic landscape of HIV-TB |
| title_short | The transciptomic landscape of HIV-TB |
| title_sort | transciptomic landscape of hiv tb |
| topic | Medicine |
| url | http://hdl.handle.net/11427/3377 |
| work_keys_str_mv | AT deffurarmin thetransciptomiclandscapeofhivtb AT deffurarmin transciptomiclandscapeofhivtb |