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The Utilization And Optimization Of Omics Trait Prediction Models Within And Across Diverse Populations, Ashley Mulford Jan 2021

The Utilization And Optimization Of Omics Trait Prediction Models Within And Across Diverse Populations, Ashley Mulford

Master's Theses

Most cancer chemotherapeutic agents are ineffective in a subset of patients; thus, it is important to consider the role of genetic variation in drug response. Lymphoblastoid cell lines (LCLs) derived from 1000 Genomes Project populations of diverse ancestries are a useful model for determining how genetic factors impact variation in cytotoxicity. In our study, LCLs from three 1000 Genomes Project populations of diverse ancestries were previously treated with increasing concentrations of eight chemotherapeutic drugs and cell growth inhibition was measured at each dose with half-maximal inhibitory concentration (IC50) or area under the dose-response curve (AUC) as our phenotype for each …


Population-Matched Transcriptome Prediction Increases Discovery And Replication Rate In Twas, Elyse Geoffroy Jan 2021

Population-Matched Transcriptome Prediction Increases Discovery And Replication Rate In Twas, Elyse Geoffroy

Master's Theses

Most genome-wide and transcriptome-wide association studies (GWAS, TWAS) focus on European populations; however, these results cannot always be accurately applied to non-European populations due to differences in genetic architecture. Using summary statistics from GWAS in the Population Architecture using Genomics and Epidemiology (PAGE) study, which comprises ~50,000 Hispanic/Latinos, African Americans, Asians, Native Hawaiians, and Native Americans, we perform transcriptome-wide association studies to determine gene-trait associations. Initially, we compared results using two transcriptome prediction models derived from the Multi-Ethnic Study of Atherosclerosis (MESA) populations: the African American (AFA) model and the Hispanic/Latino (HIS) model. We identified 141 unique genome-wide significant trait-associated …


Pseudomonas Aeruginosa Prophages And Engineered Temperate Phages, Genevieve Johnson Jan 2021

Pseudomonas Aeruginosa Prophages And Engineered Temperate Phages, Genevieve Johnson

Master's Theses

The rising rate of antibiotic-resistant bacteria is a global health concern, and the Pseudomonas aeruginosa is estimated to be a leader in serious threats. Bacteriophages, or viruses that infect bacteria, have gained renewed interest in Western Medicine as an alternative to antibiotics. Phage therapy of P. aeruginosa infections has primarily focused on obligately lytic phages. However, prophages, or phages in the lysogenic life cycle, are estimated to far outnumber obligately lytic phages. In theory, these prophages can be genetically modified to be obligately lytic and thus ideal candidates for phage therapy. To date there has not been a comprehensive analysis …


Lactobacillus Metabolite-Mediated Induction Of Bacteriophage, Taylor Miller-Ensminger Jan 2021

Lactobacillus Metabolite-Mediated Induction Of Bacteriophage, Taylor Miller-Ensminger

Master's Theses

Once considered sterile in the absence of an infection, the female urinary tract is home to a diverse community (microbiota) of bacterial species and bacteriophage (phage), viruses that infect bacteria A dominant member of the female urinary microbiota is the bacterial genus Lactobacillus. Several Lactobacillus species are even associated with urinary health. Phage infectious of bacteria in the urinary tract tend to replicate through one of two life cycles: the lytic (active) life cycle or the lysogenic (dormant) life cycle. Temperate phage can switch from the lysogenic life cycle to the lytic life cycle in the presence of an environmental …