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The Genomics Of Champ1: Insights Into Their Cell-Type Specificity And Developmental Trajectories, Zoe Marie Van Caugherty

MUSC Theses and Dissertations

Chromosome alignment maintaining phosphoprotein 1(CHAMP1) is a gene that encodes a zinc finger protein that is involved in in the maintenance of kinetochore-microtubule attachment and regulating chromosome segregation in mitosis. (Itoh et al., 2011) CHAMP1 mutations have been shown to be major risk factors for neurodevelopmental disorders (NDDs) and autism spectrum disorder (ASD).(Asakura et al., 2021; Isidor et al., 2016; Levy et al., 2022) Although there is information on the link between CHAMP1 mutations and NDD, the role of CHAMP1 in regulating processes of human cortical development, namely, neurogenesis, proliferation, and electrophysiological properties of newly born neurons, is unknown. This …

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

Functionality Of The Type Vi Secretion System (T6ss) In Providencia Alcalifaciens., Katherine Hood

UVM Patrick Leahy Honors College Senior Theses

The Providencia genus is a member of the Enterobacteriaceae family of bacteria and is a set of emerging, opportunistic pathogens that are known to cause urinary tract infections and gastroenteritis (Shah et al., 2019). Specifically, Providencia alcalifaciens has been linked to several diarrheal outbreaks worldwide, raising public safety concerns (Shah et al., 2019; Shah et al., 2015; Hinenoya et al., 2009; Yoh et al., 2005). The genome of P. alcalifaciens 205/92, a clinical isolate, has been sequenced and was found to contain numerous genes with homology to many virulence factors in pathogenic Gram-negative bacteria including a type VI secretion system …

Genome-Based Pathogenicity Potential Of Salmonella Isolated From Diverse Sources, Jared Mr Crocco

Theses and Dissertations (Comprehensive)

Bacterial human pathogens are among the leading causes of death around the world, especially in low income and developing countries. One important element in a bacterium’s ability to cause disease are genes that directly contribute to pathogenicity called virulence factors. A second significant aspect are antimicrobial resistance genes which allow microorganisms to persist in the presence of antimicrobial agents. In this project I aimed to determine if Salmonella isolated from different sources differed in pathogenicity profiles based on the complement of genes identified through genomic analysis. Accordingly, Salmonella genomes were organized into 8 groups: animal, clinical, human, environmental, food, water …

Unsupervised Multi-Resolution Analysis Of Protein-Protein Abundance Patterns In Infectious Exacerbation Of Copd, Eric Everingham

Theses

Despite consistently appearing as a top 5 cause of death domestically and internationally, understandings of the underlying biological interactions of COPD remain insufficient. Particularly, early identification of highly vulnerable patients that may experience more severe infectious exacerbation is a challenge during diagnostics. This project leverages unsupervised clustering and multi-resolution decomposition of proteomic abundance profiles in a small cohort of COPD subjects to identify candidate biomarkers of heightened exacerbation risk. As part of an ongoing study, serum and sputum samples were collected during well visits (stable illness) from n=67 subjects, and analyzed using quantitative proteomics. A scores principal component analysis was …

Towards Improved Genomic Surveillance Of Organisms, Joseph L. Sevigny

Doctoral Dissertations

DNA and RNA sequencing is an indispensable tool for the surveillance and monitoring of organisms. Technological advances and research opportunities over the past several years have transformed and driven my research questions; from understanding the impacts of environmental perturbations on complex benthic communities, to tracking and understanding emerging pathogens like SARS-CoV-2. All of them revolve around the use of DNA sequencing to ask fundamental questions about our understanding genomes and their relationship to phenotype and the environment. The advent of sequencing-based characterization has revolutionized our approach to studying organismal communities on a large scale, offering the ability to analyze vast …

Genomic Characterization Of Adolescent And Young Adult Cancers: Investigation Of Ewing Sarcoma Susceptibility And Chornobyl Thyroid Tumors, Olivia Lee

Dissertations & Theses (Open Access)

Adolescent and young adult (AYA) cancers, diagnosed between the ages of 15 and 39, can exhibit distinctive genetic and molecular characteristics. Reported epidemiologic findings and treatment outcomes based on pediatric and adult cancer studies are often not suitable for application to the AYA population, underscoring the need for more thorough genomic research. Advances in sequencing technologies have enabled comprehensive analyses of complex genomic characteristics of AYA cancers, crucial for understanding the underlying biology of these malignancies. Here, I have utilized advanced sequencing techniques and integrated analytic approaches to describe important genomic features in two different AYA cancer types: Ewing Sarcoma …

Algorithmic And Computational Approaches For Improving The Efficiency Of Mobile Genomic Element Discovery, A Bioinformatics Framework, Fatema Shormin

All Theses

Through this research, we are showcasing the application of computational approaches to the discoveries in the life sciences spectrum. Our current research not only focused on mobile genetic elements but also developed the computational methods that enabled these findings. We combined the biology sciences and computer science in our research, which is essentially multidisciplinary. To that end, this research intricately probed the role and implications of mobile genetic elements, emphasizing transposable elements. These dynamic components wielded substantial influence over genomic architecture's structure, function, and evolutionary adaptations. An integral component of our study is the innovative computational tool, Target/IGE Retriever (TIGER), …

Structure V-1: A Mississippian Mica Workshop In Kershaw County, South Carolina, John Mclellan Dodge

Theses and Dissertations

This thesis reanalyzes the pottery assemblage of Structure V-1 at the Mulberry site (38KE12). Because Structure V-1 was originally hypothesized to be evidence of a late seventeenth century occupation at the Mulberry site, the framework I use for this research focuses on identifying evidence of community coalescence after Mulberry’s initial occupation ended. However, new evidence from both the pottery and radiocarbon analysis conclusively dates the structure to around the sixteenth century Mulberry I phase. With that new date in mind, I explore the role mica craft production within Structure V-1 might have had in linking the community at Mulberry to …

Predicting Marine Teleost Responses To Ocean Warming And Pollution, Akila Harishchandra

Electronic Theses and Dissertations

Ocean warming and pollution are two detrimental anthropogenic factors causing rapid marine ecosystem degradation recorded in the past decades. These factors alter the marine environment intolerable for many marine species, forcing them to either adapt or shift their contemporary habitat ranges to reduce the extinction risk embedded with environmental degradation. Estimating marine species’ habitat range shifts, and their potential for developing adaptive mechanisms are critical for ecosystem conservation and management, human health risk assessment, and climate change vulnerability assessments. Given that, for the first chapter of this thesis, we focused on developing a species distribution model (SDM) integrating marine species …

Evolution Of Overlapping Reading Frames In Virus Genomes, Laura Muñoz Baena

Electronic Thesis and Dissertation Repository

Viruses are formidable pathogens that represent the majority of biological entities in our planet, and their genomes are a source of interesting enigmas. One feature in which virus genomes are usually rich, is the presence of overlapping reading frames (OvRFs) — portions of the genome where the same nucleotide sequence encodes more than one protein. OvRFs are hypothesized to be used by viruses to encode proteins more compactly and to regulate transcription. In addition, OvRFs might be a source of gene novelty, facilitating the creation of new open reading frames (ORF) within the transcriptional context of existing ones.

To characterize …

Metagenomic Investigation Of Microbial Dark Carbon Fixation, Viral Interactions, And Horizonal Gene Transfer Within A Convergent Margin Subsurface Ecosystem, Timothy Joseph Rogers

Doctoral Dissertations

Convergent margins are geological regions where two or more tectonic plates collide, and the denser “subducting slab” is pushed beneath the less dense overriding plate. As the slab descends, it devolatilizes under higher temperatures and pressures, allowing dissolved inorganic carbon (DIC) and redox active volatile rich fluids to cycle between the upper crust and Earth’s mantle. These fluids migrate through cracks and fissures in the upper mantle and crust, fueling chemolithoautotrophy-based microbial ecosystems in the subsurface before they are expelled on the surface in the form of hydrothermal seeps and springs. Chemolithoautotrophic ecosystems, such as those in the Costa Rican …

Sequestered Sequences: A Bioinformatic Approach To The Forgotten Genome, Dylan Barth

UNLV Theses, Dissertations, Professional Papers, and Capstones

As high throughput sequencing generates ever increasing amounts of genetic and epigenetic data new lines of inquiry open up in the field of genomic research. In this thesis, we discuss three ways in which we can utilize public databases of next generation genomic data in order to study areas of the genome previously ignored by traditional approaches. These include the study of linker regions between domains of proteins, indirect enhancers that do not strongly contact promoters of genes they regulate, and transposon-derived enhancer elements. The work uncovers many exceptions to known biological principles, and adds nuance to our understanding of …

An Evolutionary Comparative Study Of Congenital Stationary Night Blindness-Associated Trpm1 Genetic Variants Of Uncertain Significance In Horses And Humans Utilizing Caenorhabditis Elegans, Gabrielle Davis

Theses

Congenital stationary night blindness (CSNB) is a heterogeneous collection of genetic diseases affecting the eyes and vision in horses and humans. Current research has implicated several genetic mutations impacting different genes involved in phototransduction and signal transmission, including TRPM1. In horses, genetic mutations in TRPM1 also result in a leopard spotting pattern or leopard complex. The goal of this study is to examine the potential impact of CSNB associated TRPM1 missense variants of uncertain significance (VUS). Previous research in Caenorhabditis elegans have revealed an orthologous TRPM1 gene known as gon-2 that allows for comparative studies. The evolutionary relationship of …

Exploration Of The Immune Landscape Of Ebv-Associated Gastric Cancers, Mikhail Salnikov

Electronic Thesis and Dissertation Repository

Epstein–Barr virus (EBV) is a gammaherpesvirus associated with 9% of all gastric cancers (GCs). EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology and patient prognosis. The purpose of this thesis is to investigate the tumor microenvironment (TME) of EBVaGCs, which has not been explored in-depth. We hypothesize that EBVaGCs and EBVnGCs are also distinct in terms of the molecular immune landscape. We employed over 400 stomach adenocarcinoma (STAD) samples from The Cancer Genome Atlas (TCGA), as well as a single cell dataset, for the construction of a web suite …

Mining Sars-Cov-2 Phylogenetic Trees To Estimate Circulating Infections And Patterns Of Migration, Erin V. Brintnell

Electronic Thesis and Dissertation Repository

The SARS-CoV-2 pandemic led to the formation of very large databases of genomic viral data. These databases contain information on transmission dynamics, emergence and evolution of SARS-CoV-2. However, extracting this information from sequences is difficult, as most methods of analyzing viral genomes were developed for smaller data sets. Therefore, my objective was to develop new fast estimators of the number of infections (I) and the rate of migration based on simple features of SARS-CoV-2 phylogenies.

I simulated pathogen evolution using a susceptible-exposed-infectious-recovered (SEIR) model of pathogen spread, reconstructing evolution using CoVizu. For simulations of I, I varied the total number …

Utilizing Natural Language Processing For Automated Clinical Text Review: Identification Of Care Preference Documentation In Patients’ Discharge Summaries, Saksham Arora

Computer Science Senior Theses

Improving patient-centered care necessitates accurate documentation of care preferences, a crucial aspect often underrepresented in administrative data. Most studies apply care documentation to specific patient populations, rather than more appropriately broad population of `seriously ill' patients. This paper addresses this gap by leveraging transformer-based machine learning models, exhibiting an improvement over traditional keyword-based search methods in identifying care preference documentation.

In order to capture a broad spectrum of seriously ill patients, we matched decedent patients to non-decedent counterparts by utilizing a propensity score matching, accounting for important variables like age, gender, primary diagnoses and commodities. We trained and fine-tuned Bio_ClinicalBERT …

Understanding Host-Microbe Interactions In Maize Kernel And Sweetpotato Leaf Metagenomic Profiles., Alison K. Adams

Doctoral Dissertations

Functional and quantitative metagenomic profiling remains challenging and limits our understanding of host-microbe interactions. This body of work aims to mediate these challenges by using a novel quantitative reduced representation sequencing strategy (OmeSeq-qRRS), development of a fully automated software for quantitative metagenomic/microbiome profiling (Qmatey: quantitative metagenomic alignment and taxonomic identification using exact-matching) and implementing these tools for understanding plant-microbe-pathogen interactions in maize and sweetpotato. The next generation sequencing-based OmeSeq-qRRS leverages the strengths of shotgun whole genome sequencing and costs lower that the more affordable amplicon sequencing method. The novel FASTQ data compression/indexing and enhanced-multithreading of the MegaBLAST in Qmatey allows …

Computational Analysis Of Microbial Sequence Data Using Statistics And Machine Learning, Zhixiu Lu

Doctoral Dissertations

Since the discovery of the double helix of DNA in 1953, modern molecular biology has opened the door to a better understanding of how genes control chemical processes within cells, including protein synthesis. Although we are still far from claiming a complete understanding, recent advances in sequencing technologies, increased computational capacity, and more sophisticated computational methods have allowed the development of various new applications that provide further insight into DNA sequence data and how the information they encode impacts living organisms and their environment. Sequencing data can now be used to start identifying the relationships between microorganisms, where they live, …

Integrating Omim And Intact Data For The Analysis Of Gene-Phenotype Interactions In Complex Diseases: A Linux-Based Computational Tool For Network Analysis, Devin Keane

All Theses

The field of genetics is constantly evolving. New advances in bioinformatics and computational approaches are leading to exciting new developments in our ability to treat and prevent diseases. Computational genetics provides valuable insights into the complex mechanisms and layers of biological communication that shape an organism's phenotype. Understanding these mechanisms is critical to advancing human health.

The study of diseases in genetics requires a comprehensive understanding of the interactions between various biological processes, including gene expression, protein synthesis, RNA, metabolism, and cell-cell communication. To effectively address the root causes of such diseases, multi-disciplinary approaches that integrate information from different levels …

Deephtlv: A Deep Learning Framework For Detecting Human T-Lymphotrophic Virus 1 Integration Sites, Johnathan Jia, Johnathan Jia

Dissertations & Theses (Open Access)

In the 1980s, researchers found the first human oncogenic retrovirus called human T-lymphotrophic virus type 1 (HTLV-1). Since then, HTLV-1 has been identified as the causative agent behind several diseases such as adult T-cell leukemia/lymphoma (ATL) and a HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). As part of its normal replication cycle, the genome is converted into DNA and integrated into the genome. With several hundreds to thousands of unique viral integration sites (VISs) distributed with indeterminate preference throughout the genome, detection of HTLV-1 VISs is a challenging task. Experimental studies typically use molecular biology …

Microbiome Recovery Of The Upper Clark Fork River Restoration Site, Danella Stapley

Graduate Theses & Non-Theses

Soil microorganisms provide ecosystem functions and services critical for life, can have lasting effects on aboveground plant communities, and can serve as indicators of soil quality. However, biotic indicators are underrepresented in soil health assessments. Incorporating microbial soil evaluations in ecological restoration studies are important in order to obtain a more comprehensive understanding about their role in healthy soil development. In this study, we used three bioindicators to assess the post-restoration soil microbiome recovery of the Upper Clark Fork River: extracellular soil enzyme activity, microbial biomass, and microbiome community and diversity. We found that microbiome recovery rate varied at different …

Investigating The Role Of Spatial Compartmentalization And Genomic Translocations In Metastatic Cancer: A Multi-Omic Analysis, Joshua Harris Garretson

Chancellor’s Honors Program Projects

No abstract provided.

Application Of Informatics Tools To Facilitate The Practice Of Precision Medicine With Genomic Testing And Clinical Data, Michael Sayer

Pharmaceutical Sciences (PhD) Dissertations

The practice of precision medicine considers a variety of sources of information to optimize patient care. Factors such as patient demographics, clinical history, and lab test values have well understood effects on treatment outcomes and influence decision making. However, effective inclusion of biomolecular data such as protein expression and DNA sequencing data within the practice of precision medicine needs continued study. Informatics tools offer solutions to allow these complex data sources to be effectively embraced. Utilization of informatics tools to visualize data pertaining to the gene selection practices of pharmacogenomic (PGx) tests effectively communicated large amounts of information into concise …

Bioinformatic Analysis Of Mirna Mechanisms In Circadian Rhythm Using A Zebrafish (Danio Rerio) Model, Layton F. Coursey

Honors College Theses

MicroRNAs are noncoding RNAs found in cells and the bloodstream, which help to maintain proper protein production and overall gene expression1. Typically, microRNAs bind to messenger RNA (mRNA) in the cell cytoplasm, acting as post-transcriptional regulators, and either degrade or repress mRNA2. Due to microRNAs playing a vital role in gene expression by repressing protein production of target genes, if they are underexpressed then the protein it regulates could be overexpressed as a result.

miRNAs have the potential to be biomarkers for numerous neurodegenerative diseases. Neurodegeneration can be seen in many forms such as Dementia, Alzheimer’s (AD), Huntington’s Disease (HD), …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Targeted Mapping Of Oryza Sativa Chilling Tolerance Candidate Genes Using Multiple Stress-Relevant Quantitative Traits, Naoki Simon Shimoyama

Dissertations (1934 -)

Developing chilling tolerant accessions of domesticated Asian rice is a potential source of significant crop improvement to address the needs of a growing global population. The uniquely chilling sensitive nature of the tropically originating Oryza sativa make it the most important staple crop that could gain the maximum benefit from improved tolerance to low temperature stress. However, mechanisms underlying this complex trait are not fully understood. Oryza sativa has two major varietal groups with different levels of chilling tolerance, JAPONICA and INDICA, providing an ideal tool to investigate mechanistic differences in the chilling stress tolerance responses within this important crop …

Taxonomic Classification Of Viral And Bacterial Dna Following 2021 Avian Mass Mortality Event, Tessa Baillargeon

Honors Theses and Capstones

From May through July 2021, an unusual mortality event occurred along the eastern coast and Midwest of the United States. Thousands of birds, mostly from the order Passeriformes, were part of the die-off including blue jays (Cyanocitta cristata), common grackles (Quiscalus quiscula), European starlings (Sturnus vulgaris), American robins (Turdus migratorius). Clinical signs included crusted eyes, swollen conjunctiva, otitis, seizures, and ataxia.

The New Hampshire Veterinary Diagnostic Laboratory (NHVDL) received over 100 affected birds from various collaborators throughout the United States including Washington DC, NJ, CT, MD, and OH. Given the timing and geologic …

Mechanisms Linking The Circadian Clock To Cardiac Physiology, Lamario J. Williams

All ETDs from UAB

Rationale: Cardiovascular disease continues to be the leading cause of death in America. Many aspects of both cardiovascular physiology (e.g., blood pressure, heart rate) and pathophysiology (e.g., myocardial infarctions, sudden cardiac death) exhibit time-of-day dependent fluctuations (termed diurnal variations). Circadian clocks consist of transcriptional feedback cascades directly modulating expression of genes involved in processes such as metabolism, signaling, and ion transport. Interestingly, genetic deletion of a core circadian clock component in the heart (cardiomyocyte-specific Bmal1 knockout mice) leads to chronic induction of the transcriptional repressor E4 Promoter-Binding Protein 4 (E4BP4) associated with early-onset dilated cardiomyopathy, metabolic inflexibility, and electrophysiologic disturbances. …

Cluster Homolog Of Immunoglobulin-Like Receptor Genes In Chicken Immune Responses, Brandi A. Sparling

Graduate Theses, Dissertations, and Problem Reports

This dissertation explores the identity and role of immunoglobulin-like (Ig-like) receptors in chickens, with focus on their implications in disease and disease progression. These receptors, wisely expressed across immune cells, interact with the major histocompatibility complex (MHC) class I molecules to modulate immune responses in mammals. Due to the insufficient representation of chicken Ig-like receptors in online databases, this study systematically annotates the chicken Cluster Homolog of Immunoglobulin-like Receptors (CHIR) genes using advanced bioinformatic techniques, aligning with the release of the 7th edition of the chicken genome assembly that comprises builds for a broiler and layer chicken. The analysis identifies …