a tics meta-analysis of differ en ti ally expressed genes in colorectal cancer
TRANSCRIPT
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A BIOINFORMATICS META-ANALYSIS OF DIFFERENTIALLY EXPRESSED
GENES IN COLORECTAL CANCER
by
SIMON KIT CHAN
B.Sc. First Class Honours, Cell and Molecular Biology,
Simon Fraser University, 2005
A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS
FOR THE DEGREE OF
MASTER OF SCIENCE
in
THE FACULTY OF GRADUATE STUDIES
(Bioinformatics)
THE UNIVERSITY OF BRITISH COLUMBIA
December 2007
Simon Kit Chan, 2007
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ii
Abstract
BACKGROUND: Elucidation of candidate colorectal cancer biomarkers often
begins by comparing the expression profiles of cancerous and normal tissue by
performing high throughput gene expression profiling. While many such studies
have been performed, the resulting lists of differentially expressed genes tend to
be inconsistent with each other, suggesting that there are some false positives
and negatives. One logical solution to this problem is to determine the
intersection of the lists of differentially expressed genes from independent
studies. It is expected that genes that are biologically relevant to cancer
tumorigenesis will be reported most often, while sporadically reported genes are
due to the inherent biases and limitations of each of the profiling platforms used.
However, the statistical significance of the observed intersection among many
independent studies is usually not considered. PURPOSE: To address these
issues, we developed a computational meta-analysis method that ranked
differentially expressed genes based on the following criteria, which are
presented in order of importance: the amount of intersection among studies, total
tissue sample sizes, and average fold change in expression. We applied this
meta-analysis method to 25 independent colorectal cancer profiling studies that
compared cancer versus normal, adenoma versus normal, and cancer versus
adenoma tissues. RESULTS: We observed that some genes were consistently
reported as differentially expressed with a statistically significant frequency (P