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    Integration of Genome Scale Data for Identifying New Biomarkers in Colon Cancer: Integrated Analysis of Transcriptomics and Epigenomics Data from High Throughput Technologies in Order to Identifying New Biomarkers Genes for Personalised Targeted Therapies for Patients Suffering from Colon Cancer

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    Author
    Hassan, Aamir Ul
    Supervisor
    Peng, Yonghong
    Keyword
    Colon cancer
    Microarray gene expression profiling
    Gene ontology enrichment analysis
    MicroRNA
    System biology
    Bioinformatics
    Gene signature
    Cross-validation
    Diagnostic
    Prognostic
    Rights
    Creative Commons License
    The University of Bradford theses are licenced under a Creative Commons Licence.
    Institution
    University of Bradford
    Department
    Faculty of Engineering and Informatics
    Awarded
    2017
    
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    Abstract
    Colorectal cancer is the third most common cancer and the leading cause of cancer deaths in Western industrialised countries. Despite recent advances in the screening, diagnosis, and treatment of colorectal cancer, an estimated 608,000 people die every year due to colon cancer. Our current knowledge of colorectal carcinogenesis indicates a multifactorial and multi-step process that involves various genetic alterations and several biological pathways. The identification of molecular markers with early diagnostic and precise clinical outcome in colon cancer is a challenging task because of tumour heterogeneity. This Ph.D.-thesis presents the molecular and cellular mechanisms leading to colorectal cancer. A systematical review of the literature is conducted on Microarray Gene expression profiling, gene ontology enrichment analysis, microRNA and system Biology and various bioinformatics tools. We aimed this study to stratify a colon tumour into molecular distinct subtypes, identification of novel diagnostic targets and prediction of reliable prognostic signatures for clinical practice using microarray expression datasets. We performed an integrated analysis of gene expression data based on genetic, epigenetic and extensive clinical information using unsupervised learning, correlation and functional network analysis. As results, we identified 267-gene and 124-gene signatures that can distinguish normal, primary and metastatic tissues, and also involved in important regulatory functions such as immune-response, lipid metabolism and peroxisome proliferator-activated receptors (PPARs) signalling pathways. For the first time, we also identify miRNAs that can differentiate between primary colon from metastatic and a prognostic signature of grade and stage levels, which can be a major contributor to complex transcriptional phenotypes in a colon tumour.
    URI
    http://hdl.handle.net/10454/17419
    Type
    Thesis
    Qualification name
    PhD
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    Theses

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