Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.786331
Title: Analysis of microarray and next generation sequencing data for classification and biomarker discovery in relation to complex diseases
Author: Elyasigomari, Vahid
ISNI:       0000 0004 7971 7951
Awarding Body: Queen Mary University of London
Current Institution: Queen Mary, University of London
Date of Award: 2017
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Abstract:
This thesis presents an investigation into gene expression profiling, using microarray and next generation sequencing (NGS) datasets, in relation to multi-category diseases such as cancer. It has been established that if the sequence of a gene is mutated, it can result in the unscheduled production of protein, leading to cancer. However, identifying the molecular signature of different cancers amongst thousands of genes is complex. This thesis investigates tools that can aid the study of gene expression to infer useful information towards personalised medicine. For microarray data analysis, this study proposes two new techniques to increase the accuracy of cancer classification. In the first method, a novel optimisation algorithm, COA-GA, was developed by synchronising the Cuckoo Optimisation Algorithm and the Genetic Algorithm for data clustering in a shuffle setup, to choose the most informative genes for classification purposes. Support Vector Machine (SVM) and Multilayer Perceptron (MLP) artificial neural networks are utilised for the classification step. Results suggest this method can significantly increase classification accuracy compared to other methods. An additional method involving a two-stage gene selection process was developed. In this method, a subset of the most informative genes are first selected by the Minimum Redundancy Maximum Relevance (MRMR) method. In the second stage, optimisation algorithms are used in a wrapper setup with SVM to minimise the selected genes whilst maximising the accuracy of classification. A comparative performance assessment suggests that the proposed algorithm significantly outperforms other methods at selecting fewer genes that are highly relevant to the cancer type, while maintaining a high classification accuracy. In the case of NGS, a state-of-the-art pipeline for the analysis of RNA-Seq data is investigated to discover differentially expressed genes and differential exon usages between normal and AIP positive Drosophila datasets, which are produced in house at Queen Mary, University of London. Functional genomic of differentially expressed genes were examined and found to be relevant to the case study under investigation. Finally, after normalising the RNA-Seq data, machine learning approaches similar to those in microarray was successfully implemented for these datasets.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.786331  DOI: Not available
Keywords: Engineering and Material Science ; gene expression profiling ; next generation sequencing ; microarray
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