Title page for ETD etd-05222006-155528


Type of Document Dissertation
Author Sha, Wei
URN etd-05222006-155528
Title Microarray data analysis methods and their applications to gene expression data analysis for Saccharomyces cerevisiae under oxidative stress
Degree PhD
Department Genetics, Bioinformatics, and Computational Biology
Advisory Committee
Advisor Name Title
Mendes, Pedro J. P. Committee Chair
Gibas, Cynthia J. Committee Member
Sible, Jill C. Committee Member
Tyson, John J. Committee Member
Ye, Keying Committee Member
Keywords
  • oxidative stress
  • microarray data analysis
  • cumeme hydroperoxide
  • Yap1
Date of Defense 2006-05-12
Availability unrestricted
Abstract
Oxidative stress is a harmful condition in a cell, tissue, or organ, caused by an imbalance between reactive oxygen species or other oxidants and the capacity of antioxidant defense systems to remove them. These oxidants cause wide-ranging damage to macromolecules, including proteins, lipids, DNA and carbohydrates. Oxidative stress is an important pathophysiologic component of a number of diseases, such as Alzheimer’s disease, diabetes and certain cancers. Cells contain effective defense mechanisms to respond to oxidative stress. Despite much accumulated knowledge about these responses, their kinetics, especially the kinetics of early responses is still not clearly understood.

The Yap1 transcription factor is crucial for the normal response to a variety of stress conditions including oxidative stress. Previous studies on Yap1 regulation started to measure gene expression profile at least 20 minutes after the induction of oxidative stress. Genes and pathways regulated by Yap1 in early oxidative stress response (within 20 minutes) were not identified in these studies.

Here we study the kinetics of early oxidative stress response induced by the cumene hydroperoxide (CHP) in Saccharomyces cerevisiae wild type and yap1 mutant. Gene expression profiles after exposure to CHP were obtained in controlled conditions using Affymetrix Yeast Genome S98 arrays. The oxidative stress response was measured at 8 time points along 120 minutes after the addition of CHP, with the earliest time point at 3 minute after the exposure. Statistical analysis methods, including ANOVA, k-means clustering analysis, and pathway analysis were used to analyze the data. The results from this study provide a dynamic resolution of the oxidative stress responses in S. cerevisiae, and contribute to a richer understanding of the antioxidant defense systems. It also provides a global view of the roles that Yap1 plays under normal and oxidative stress conditions.

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