(Georgia Institute of Technology, 2016-05)
Kim, Renaid B.
Amyotrophic lateral sclerosis (ALS) is a debilitating disease that is characterized by late-onset, progressive neuronal degeneration of the motor neurons, which results in dysphagia, dyspnea, dysarthria and eventually death. There is currently no cure for ALS, with riluzole being the only FDA-approved drug that only extends survival by 3 to 6 months without repairing the damaged motor neurons. Transgenic mice, especially the one with superoxide dismutase 1 glycine 93 to alanine mutation (SOD1-G93A), have been a mainstay in the study of ALS and its underlying pathophysiology, with more than 3,000 articles upon a Pubmed search of (Amyotrophic Lateral Sclerosis OR ALS) AND (G93A OR Mouse).
Such a wealth of data allows for informatics approaches to understanding the pathophysiology of ALS. To form a framework for conducting an informatics study with primary journal articles about ALS, a nine-category ontology was created via a comprehensive, keyword-based agnostic survey of more than 1,300 journal articles, which is presented in Chapter 2. A meta-analysis of 45 journal articles was conducted to examine temporal relationships between calcium homeostasis, mitochondrial dysfunction and oxidative stress and to elucidate the timing of the disturbances, which is presented in Chapter 3. Chapter 4 thoroughly describes the biocuration process used for the projects in the laboratory and presents interesting findings about the associates in the laboratory.