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December 2018
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Mr Stephen Pederson

Honours graduate

 

Honours thesis

FOXP3 and regulatory T cells: A meta-analysis of microarray data

Microarrays are a relatively recent and increasingly widespread tool used in the analysis of gene expression data, able to give a measure of the abundance of specific mRNA transcripts in a biological sample. By comparing this measure across different biological conditions, a picture of changes in gene expression levels, as related to the underlying biology, can be obtained. As an increasing amount of microarray data is being generated by independent laboratories around the world, public repositories have arisen, such as Gene Expression Omnibus () (Edgar, R. et al, 2002) and ArrayExpress (), (Brazma, A. et al, 2003) where researchers are able to share their data. In this project, datasets sourced from GEO and ArrayExpress have been reanalysed where possible, and the multiple datasets combined for a meta-analysis. Multiple inter-related public databases also exist for sequence level data with the two main umbrella organizations being the American National Center for Biotechnology Information (NCBI), which houses the Entrez, Unigene and RefSeq databases amongst other resources (Wheeler, D. et al, 2007), and the European Bioinformatics Institute (EBI), which houses resources including the multiple layers of the Ensembl Database (Hubbard, T. et al, 2007). In this analysis, Entrez Gene is the principal source of information, as it houses annotated data about genes from completely sequenced genomes (Maglott, D. et al 2007), as opposed to the expressed sequences that form the basis of databases such as Unigene (Wheeler, D. et al, 2007). The biological system under investigation is that of Regulatory T Cells (Tregs) versus Helper T cells (Thelp). Regulatory T Cells play a vital role in preventing the immune system from attacking the body, whilst still allowing foreign invaders such as bacteria and viruses to be destroyed. Failure of Treg cells to completely fulfil this function can result in a variety of autoimmune diseases such as Type-I diabetes (T1D) and immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX). The transcription factor Foxp3 plays a key role in Treg lineage specification (Fontenot, J.D. et al, 2005), and maintenance (Williams, L. M. and A. Y. Rudensky, 2007). The genes under the regulatory control of Foxp3 are the targets of this investigation. Chapters 2 and 3 of this thesis introduce the background information and review the current literature for both microarray technology and Treg lineage specification. The subsequent analysis and discussion is presented in chapters 4 through 7.