Date

August 2013

Document Type

Thesis

Degree Name

M.S.

Department

Dept. of Medical Informatics and Clinical Epidemiology

Institution

Oregon Health & Science University

Abstract

Ionizing radiation (IR) is commonly used in the treatment of cancer through radiation therapy. In addition, exposure to IR is a vital safety risk that nuclear workers constantly face. The effect of IR on human cell, both normal and malignant, is biologically significant. The purpose of this study is three fold: 1) to determine which genes are differentially expressed in cells exposed to radiation, 2) to discover critical pathways affected by these genes, 3) and identify drugs that significantly target the differentially expressed pathways. The raw data for this study consists of 5 Gene Expression Omnibus (GEO) data sets that contain microarray expression data for normal or cancerous cell lines exposed to IR. A secondary analysis on these data sets utilizes various Bioconductor R packages in the analysis of genes that are differentially expressed and the identification of critical pathways. Numerous genes and pathways were found to be differentially expressed in this analysis. In addition, six pathways were differentially expressed across all cancer cell data sets. No pathways that were differentially expressed across all normal cell data sets. The critical Reactome pathways that were significant across all cancer cell data sets are the following: 1) "Cell Cycle, Mitotic", 2) "DNA Replication", 3) "Mitotic M-M/G1 phases", 4) "AKT phosphorylates targets in the cytosol", 5) "M Phase", 6) "Mitotic Prometaphase". A drug pathway analysis was performed on these pathways and the genes that were differentially expressed and members of these pathways. The drug pathway analysis found that six significant gene targets. These six gene targets are: POLA1, POLA2, PLK1, CENPE, AURKB, CDKN1B, and RB1. The results of our study are significant because they allow x for the identification of potential genes and pathways that could be used as genetic markers in radiation therapy. In addition, the identification of drug targets will allow for testing to determine if drugs that target these genes affect the radioresistance or radiosensitivity of cancerous cells upon exposure to IR.

Identifier

doi:10.6083/M4NV9G84

Division

Div. of Bioinformatics and Computational Biology

School

School of Medicine

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