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TESTING FOR DIFFERENTIALLY EXPRESSED GENES AND KEY BIOLOGICAL CATEGORIES IN DNA MICROARRAY ANALYSIS

SARTOR, MAUREEN A

Abstract Details

2007, PhD, University of Cincinnati, Medicine : Biostatistics (Environmental Health).
DNA microarrays are a revolutionary technology able to measure the expression levels of thousands of genes simultaneously, providing a snapshot in time of a tissue or cell culture’s transcriptome. Although microarrays have been in existence for several years now, research is yet ongoing for how to best analyze the data, at least partly due to the combination of small sample sizes (few replicates) with large numbers of genes. Several challenges remain in maximizing the amount of biological information attainable from a microarray experiment. The key components of microarray analysis where these challenges lie are experimental design, preprocessing, statistical inference, identifying expression patterns, and understanding biological relevance. In this dissertation we aim to improve the analysis and interpretation of microarray data by concentrating on two key steps in microarray analysis: obtaining accurate estimates of significance when testing for differentially expressed genes, and identifying key biological functions and cellular pathways affected by the experimental conditions. We identify opportunities to enhance analytical techniques, and demonstrate that these enhancements significantly improve the functional interpretation of microarray results. We develop three related Bayesian statistical models to improve the estimates of significance by exploiting the information available from all genes, and functionally relating the gene variances to their expression levels. These novel methodologies are compared to previously proposed methods both in simulations and with real-world experimental data performed on multiple microarray platforms. In addition, we introduce a logistic regression method for identifying key biological categories and molecular pathways and compared this method with the commonly used Fisher’s exact test and other relevant previously developed methods. We make our statistical methods available to the biomedical research community through the use of statistical software widely used for microarray analysis.
Dr. Mario Medvedovic (Advisor)
143 p.

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Citations

  • SARTOR, M. A. (2007). TESTING FOR DIFFERENTIALLY EXPRESSED GENES AND KEY BIOLOGICAL CATEGORIES IN DNA MICROARRAY ANALYSIS [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1195656673

    APA Style (7th edition)

  • SARTOR, MAUREEN. TESTING FOR DIFFERENTIALLY EXPRESSED GENES AND KEY BIOLOGICAL CATEGORIES IN DNA MICROARRAY ANALYSIS. 2007. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1195656673.

    MLA Style (8th edition)

  • SARTOR, MAUREEN. "TESTING FOR DIFFERENTIALLY EXPRESSED GENES AND KEY BIOLOGICAL CATEGORIES IN DNA MICROARRAY ANALYSIS." Doctoral dissertation, University of Cincinnati, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1195656673

    Chicago Manual of Style (17th edition)