A systems biology frame work for integrating and analysing the functional role of glycosylation on immune response
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Reproducing the systems biology efforts established across areas of cell biology such as integrating biological networks with omic datasets and subjecting it to modelling analysis for studying the functional involvement of glycosylation has the potential to generate greater understanding of the complex biological mechanisms responsible for altered immune response and tolerance. In this regard, presented within this thesis is a systems biology framework, named GlycoGAIT, a database currently limited to human species which captures the mammalian glycosylation machinery in a machine readable format. GlycoGAIT captures the diverse glycan structures expressed on immune cells as well as the enzymatic reactions which leads to the synthesis of these diverse structures. GlycoGAIT, has been released as an open database, accessed freely, aiming to help researchers both within the field of glycobiology and those from related fields, to quickly identify the dysregulated glycosylation genes and associated processes important to study in inflammatory conditions. The current online version of GlycoGAIT permits the analysis of differentially expressed glycogenes under gastrointestinal inflammatory diseases and conditions, such as inflammatory bowel disease and H. pylori infection. An expansion of the potential and possibilities of GlycoGAIT has been demonstrated using open source gene expression data from Major depressive disorder (MDD), GlycoGAIT has been leveraged for the examination of alteration in glycogenes under disease conditions where inflammation is an underlying mechanism of disease pathology. Permitting, insight into the differential expression patterns of glycogenes from gastrointestinal tissues, brain tissues as well as peripheral blood mononuclear cells under MDD. This extension, demonstrating the potential of GlycoGAIT to be used both in classical biological conditions and in psychological disorders further highlights (i) the potential role played by glycosylation and (ii) the need for intuitive, open access database and analysis tools for elucidating and aiding greater understanding of glycosylation controlled and impacted biological cascades under disease states.
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