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Title: Systems biology of breast cancer
Author: Dhondalay, G. K. R.
Awarding Body: Nottingham Trent University
Current Institution: Nottingham Trent University
Date of Award: 2013
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Breast cancer, with an alarming incidence rate throughout the globe, has attracted significant investigations to identify disease specific biomarkers. Among these, oestrogen receptor (ER) occupies a central role where overexpression is a prognostic indication for breast cancer. The cross-talk between the responsible contenders of ER-associated genes potentially play an important role in the disease aetiology. Investigation of such cross talk is the focus of this thesis. The development of high throughput technologies such as expression microarrays has paved the way for investigating thousands of genes at a time. Microarrays with their high data volume, multivariate nature and non-linearity pose challenges for analysing using conventional statistical approaches. To combat these challenges, computational researchers have developed machine learning approaches such as Artificial Neural Networks (ANNs). This thesis evaluates ANNs based methodologies and their application to the analysis of microarray data generated for breast cancer cases of differing oestrogen receptor status. Furthermore they are used for network inferencing to identify interactions between ER-associated markers and for the subsequent identification of putative pathway elements. The present thesis shows that it is possible to identify some ER-associated breast cancer relevant markers using ANNs. These have been subsequently validated on clinical breast tumour samples highlighting the promise of this approach. This thesis will also demonstrate the novel application of ANNs in systems biology of ER, PR and Her2. Furthermore in this research, the integration of ER, PR and Her2 systems have been undertaken to represent a broader view of the breast cancer system. Finally, this thesis will discuss the advantages, limitations, potential application and future potential applications of the methods evaluated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available