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Articles 1 - 17 of 17
Full-Text Articles in Life Sciences
Incorporating Sex Chromosomes In Transcriptome Prediction Models And Improving Cross-Population Prediction Performance, Daniel S. Araujo
Incorporating Sex Chromosomes In Transcriptome Prediction Models And Improving Cross-Population Prediction Performance, Daniel S. Araujo
Master's Theses
Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized multivariate adaptive shrinkage may improve cross-population transcriptome prediction, as it leverages effect size estimates across different conditions - in this case, different populations. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWAS) using different methods (Elastic Net, Matrix eQTL and Multivariate Adaptive Shrinkage in R (MASHR)) and tested their out-of-sample transcriptome prediction accuracy in population-matched and cross-population scenarios. Additionally, to evaluate model applicability in …
A Population Level Examination Of The Incredible Fruit Diversity In Astragalus Lentiginosus, Quinn Thomas
A Population Level Examination Of The Incredible Fruit Diversity In Astragalus Lentiginosus, Quinn Thomas
Master's Theses
Astragalus lentiginosus is the most taxomically diverse species in the North American flora with over 40 recognized varieties. The incredible diversity within A. lentiginosus, particularly in respect to its fruit morphology, makes it an exceptional model to study adaptation and evolution. However, it remains unknown whether fruit morphology is an adaptation and, if so, the extent to which selection or neutral evolutionary processes shape the striking diversity in this trait. In order to understand the adaptive significance of fruit morphology we must first understand the genetic structure of A. lentiginosus. Varieties of A. lentiginosus vary considerably in their range size …
Comparison Of Taxonomy Assignment And Strain Detection In Urobiome Communities Using 16s Rrna Sequencing And Shotgun Metagenomic Sequencing, Delaney Sauer
Master's Theses
Advancements in sequencing technologies have enabled scientists to gain insight into the microbes that inhabit the human body, including the urinary tract. Cataloging the bacteria that inhabit the urinary tract has primarily relied on amplification and sequencing of specific variable regions of the 16S rRNA gene enabling genus-level taxonomic identification. Recently, shotgun metagenomic sequencing has been employed such that bacterial taxonomy as well as the functionality that they encode can be inferred. In this study, we compare taxonomies assigned by 16S sequencing and shotgun metagenomic sequencing of the urinary microbiota (urobiome) of females with and without a clinical diagnosis of …
Interplay Between Human Microbiota And Celiac Disease, John James Colgan
Interplay Between Human Microbiota And Celiac Disease, John James Colgan
Master's Theses
Celiac disease is an autoimmune disorder of the small intestine in which gluten, an energy-storage protein in wheat and other cereals, elicits an immune response leading to villous atrophy. Despite a strong genetic component, the disease arises sporadically over the lifetime leading us to hypothesize the microbiome might be a trigger. Here, we re-examined 16S data from 3 prior studies examining celiac disease and the microbiome with newer computational tools: the dada2 and PICRUSt 2 pipelines. Our results both confirmed findings of previous studies and generated new data regarding the celiac microbiome of India and Mexico. The datasets were also …
Exploring The Role Of Lactobacillus Jensenii And Lactobacillus Mulieris In The Urogenital Tract, Adriana Daniela Ene
Exploring The Role Of Lactobacillus Jensenii And Lactobacillus Mulieris In The Urogenital Tract, Adriana Daniela Ene
Master's Theses
Lactobacillus is a predominant species of the urogenital tract and it has been found in females with and without lower urinary tract symptoms. The Lactobacillus genus is thought to be beneficial to the host due to its capability to produce hydrogen peroxide, secondary metabolites, and lactic acid. L. jensenii is an organism frequently isolated from the urogenital tract. In March 2020, a new sister taxon of L. jensenii was described, L. mulieris. Shortly thereafter we produced a genomic analysis of all publicly available genomes (n = 43) which reclassified some L. jensenii as L. mulieris. This motivated the in-depth study …
Integrating Current Analyses Of The Breast Cancer Microbiome, Sidra Sohail
Integrating Current Analyses Of The Breast Cancer Microbiome, Sidra Sohail
Master's Theses
Breast cancer is the leading cause of cancer death for women in the US. Many cancertypes have significant associations with their resident microbial communities - emerging evidence suggests that breast cancers also interact with the local tissue-associated microbiota. Studies have examined the relationship between breast cancer and its microbiome, however, the studies varied in their approaches used to evaluate these relationships. Microbiome research advances rapidly and analysis pipelines and databases are updated frequently. This dynamic environment makes inter-study comparisons and superficial evaluations challenging as no two studies are using the same standards for evaluation. Researchers have observed the microbiota of …
Polyomavirus Jcpyv And Its Role In The Urinary Tract, Rita Lauren Mormando
Polyomavirus Jcpyv And Its Role In The Urinary Tract, Rita Lauren Mormando
Master's Theses
Polyomaviruses are the smallest closed-circular supercoiled double-stranded viruses found in the human microbiota. The polyomavirus JC (JCPyV) is most commonly found within the urinary tract, and prior studies estimate that 20-80% of older adults carry JCPyV. In very rare cases, JCPyV leaves the kidneys, causing progressive multifocal leukoencephalopathy. However, the role of JCPyV within the urinary tract remains an open question. In a prior study conducted by our group, the bladder microbiota of females with and without overactive bladder symptoms (OAB) were sequenced. Interestingly, JCPyV was only detected in females with OAB; none of the control (“asymptomatic”) microbiota contained JCPyV. …
Cataloging And Engineering Temperate Coliphages Of The Human Urinary Microbiome, Elias Crum
Cataloging And Engineering Temperate Coliphages Of The Human Urinary Microbiome, Elias Crum
Master's Theses
In the US, around 60% of females will be diagnosed with a Urinary Tract Infection (UTI) in their lifetime, and Escherichia coli is the most implicated etiological agent in UTIs. Despite its frequent association with lower urinary tract symptoms, recent studies have found that the urinary microbiome (UMB), the viral, bacterial, and fungal resident members of the urinary tract, of healthy females can also consist of E. coli. While most research has focused on the bacterial constituents of the UMB, bacteriophages, viruses that infect bacteria, are far more abundant. Bacteriophages (phages) of other human microbiomes have been shown to play …
Unveiling Bacterial Hitchhikers In The Urobiome, Genevieve Baddoo
Unveiling Bacterial Hitchhikers In The Urobiome, Genevieve Baddoo
Master's Theses
Microbial communities of bacteria, viruses, and fungi form complex interactions in nature. However, our understanding of these communities is limited to those that can be cultured in the lab. Enhanced culture methods have enabled the isolation of numerous fastidious species from urinary tract, definitively proving that the urinary tract of asymptomatic individuals is not sterile. In working with these isolates, our group has observed several instances in which a “purified” isolate actually harbors more than one species. We refer to these additional members as bacterial hitchhikers, a term previously used to describe similar occurrences in soil communities. I hypothesized that …
The Utilization And Optimization Of Omics Trait Prediction Models Within And Across Diverse Populations, Ashley Mulford
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
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
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
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 …
Optimizing Gene Expression Prediction And Omics Integration In Populations Of African Ancestry, Paul Chukwuebuka Okoro
Optimizing Gene Expression Prediction And Omics Integration In Populations Of African Ancestry, Paul Chukwuebuka Okoro
Master's Theses
Popular transcriptome imputation methods such as PrediXcan and FUSIon use parametric linear assumptions, and thus are unable to flexibly model the complex genetic architecture of the transcriptome. Although non-linear modeling has been shown to improve imputation performance, replicability and potential cross-population differences have not been adequately studied. Therefore, to optimize imputation performance across global populations, we used the non-linear machine learning (ML) models random forest (RF), support vector regression (SVR), and K nearest neighbor (KNN) to build transcriptome imputation models, and evaluated their performance in comparison to elastic net (EN). We trained gene expression prediction models using genotype and blood …
Effects Of Pharmaceutical Contamination On Sedment Microbial Communities In Streams, Benjamin Joseph Lorentz
Effects Of Pharmaceutical Contamination On Sedment Microbial Communities In Streams, Benjamin Joseph Lorentz
Master's Theses
The objective of this study was to examine the interaction of pharmaceuticals and personal care products (PPCP) and microbial communities in freshwater ecosystems. This study included two components. The first component consisted of an artificial stream study in which sediment was exposed to environmentally relevant concentrations of three different pharmaceuticals (diphenhydramine, ciprofloxacin, and fluoxetine) individually and as a mixture. Pharmaceutical exposure had no effect on denitrification rates or respiration rates in the sediments, and sediment microbial community composition showed only slight differences between streams dosed with pharmaceuticals and control streams. The second component consisted of a field study in which …
The Role Of Phage Trnas In The Evolution Of Codon Usage Biases In Giant Pseudomonas Phage Phikz And El, Stephanie Steidel
The Role Of Phage Trnas In The Evolution Of Codon Usage Biases In Giant Pseudomonas Phage Phikz And El, Stephanie Steidel
Master's Theses
As the most abundant and diverse biological agents in the biosphere phage have significant roles in microbial ecology, acting both as lethal bacterial parasites and vehicles of horizontal gene transfer. Phage/host coevolution drives optimization of phage codon usage for use of host translational machinery, thus lowered correspondence between phage and host codon usage reduces viral fitness. Some phage may partially bypass host translational selection on their codon usage by encoding their own tRNAs, although the effects of these tRNAs on phage codon usage and translation has not been well examined. This work explores the influence of phage encoded tRNAs on …
Evolution Of Interactomes, Monica Micek
Evolution Of Interactomes, Monica Micek
Master's Theses
Protein-protein interactions are part of all biological processes and are responsible for directing the development and maintenance of all systems in a species. Identifying such interactions provides insight into molecular processes in addition to their importance in understanding disease. Identifying protein-protein interactions experimentally is expensive, both in terms of cost and effort, and can generate erroneous results. Thus computational methods are key in reducing the scope of experimental assays, providing predictions for subsequent verification. Herein I present a new computational tool for the prediction of protein-protein interactions which, looking at sequence data alone, can identify putative interacting proteins as a …