Systematic Approaches for Modelling and Visualising Responses to Perturbation of Transcriptional Regulatory Networks

UoM administered thesis: Phd

  • Authors:
  • Nam Shik Han

Abstract

One of the greatest challenges in modern biology is to understand quantitatively the mechanisms underlying messenger Ribonucleic acid (mRNA) transcription within the cell. To this end, integrated functional genomics attempts to use the vast wealth of data produced by modern large scale genomic projects to understand how the genome is deployed to create a diversity of tissues and species. The expression levels of tens or hundreds of thousands genes are profiled at multiple time points or different experimental conditions in the genomic projects. The profiling results are deposited in large scale quantitative data files that are not possible to analyse without systematic computational methods. In particular, it is much more difficult to experimentally measure the concentration level of transcription factor proteins and their affinity for the promoter region of genes, while it is relatively easy to measure the result of transcription using experimental techniques such as microarrays. In the absence of such biological experiments, it becomes necessary to use in silico techniques to determine the transcription factor regulatory activities given existing gene expression profile data. It therefore presents significant challenges and opportunities to the computer science community. This PhD Project made use of one such in silico technique to determine the differences (if any) in transcription factor regulatory activities of different experimental conditions and time points.The research aim of the Project was to understand the transcriptional regulatory mechanism that controls the sophisticated process of gene expression in cells. In particular, differences in the downstream signalling from which transcription factors can play a role in predisposition to diseases such as Parasitic disease, Cancer, and Neuroendocrine disease. To address this question I have had access to large integrated genomics datasets generated in studies on parasitic disease, lung cancer, and endocrine (hormone) disease. The current state-of-the-art takes existing knowledge and asks "How do these data relate to what we already know?" By applying machine learning approaches the project explored the role that such data can play in uncovering new biological knowledge.

Details

Original languageEnglish
Awarding Institution
Supervisors/Advisors
Award date1 Aug 2013