Cluster-Based Analysis of Retinitis Pigmentosa Candidate Modifiers Using Drosophila Eye Size and Gene Expression Data

James Amstutz, Purdue University

Abstract

The goal of this thesis is to algorithmically identify candidate modifiers for retinitis pigmentosa (RP) to help improve therapy and predictions for this genetic disorder that may lead to a complete loss of vision. A current research by (Chow et al., 2016) focused on the genetic contributors to RP by trying to recognize a correlation between genetic modifiers and phenotypic variation in female Drosophila melanogaster,or fruit flies. In comparison to the genome-wide association analysis carried out in Chow et al.’s research, this study proposes using a K-Means clustering algorithm on RNA expression data to better understand which genes best exhibit characteristics of the RP degenerative model. Validating this algorithm’s effectiveness in identifying suspected genes takes priority over their classification. This study investigates the linear relationship between Drosophila eye size and genetic expression to gather statistically significant, strongly correlated genes from the clusters with abnormally high or low eye sizes. The clustering algorithm is implemented in the R scripting language, and supplemental information details the steps of this computational process. Running the mean eye size and genetic expression data of 18,140 female Drosophilagenes and 171 strains through the proposed algorithm in its four variations helped identify 140 suspected candidate modifiers for retinal degeneration. Although none of the top candidate genes found in this study matched Chow’s candidates, they were all statistically significant and strongly correlated, with several showing links to RP. These results may continue to improve as more of the 140 suspected genes are annotated using identical or comparative approaches.

Degree

M.Sc.

Advisors

Yoo, Purdue University.

Subject Area

Bioinformatics|Cellular biology|Genetics

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