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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 …

The Hepatic Immunological Pattern Shaped By Dominant-Subdominant Cellular Interactions Creates A Collective Function Beyond The Function Of Each Cellular Constituent To Orchestrate Progression Of Hepatocellular Carcinoma, Nicholas J. Koelsch

Theses and Dissertations

Abundance of data on the role of inflammatory immune responses in the progression or inhibition of hepatocellular carcinoma (HCC) has failed to offer a curative immunotherapy for HCC. This is largely because of taking reductionist approaches and missing the collective function of the hepatic immune system by focusing on specific immune cell types. To this end, we propose that focusing on the dominant-subdominant patterns of the immune cells would allow understanding of the mechanism by which a collective immune function emerges. To identify the collective immune function through a systems immunology perspective, we performed high-throughput analysis of snRNAseq data collected …

Microbial Ecology Of Urban Sewers, Emily Lou Lamartina

Theses and Dissertations

Municipal sewage provides a glimpse into the health and activities of a human society. For more than a century, sewage exploration has helped expose the sources of disease outbreaks and track disease progression over time. Recent advancements in wastewater surveillance born from the COVID-19 pandemic have potential to enhance mitigation efforts against the decades-long global health crisis of microbial antibiotic resistance. However, critical knowledge gaps exist in wastewater surveillance, stemming from a lack of understanding in sewer microbial ecology. Ecology reveals trends in how communities respond and adapt to change, which has far-reaching implications for identifying effective strategies for disease …

Peromyscus Maniculatus Bairdii And Peromyscus Maniculatus Sonoriensis Polymorphisms, Matthew Dixon Lucius

Theses and Dissertations

Sequencing technology has advanced greatly over the past couple of decades. This has led to many studies developing hypotheses based on genomic data. This requires many genomic studies to have up-to-date information on the species’ or subject’s genome being investigated. If a study does not have accurate or up-to-date background information, then they cannot fully develop their theories that are being established. In this study, I utilize outbred Peromyscus maniculatus, deer mice that are genetically diverse, to record the polymorphisms that are found throughout the Peromyscus maniculatus genome. I first explore the differences between the polymorphisms found in Peromyscus …

Methods And Tools To Improve Performance Of Plant Genome Analysis, Drew Ferrell

Theses and Dissertations

Multi -omics data analysis and integration facilitates hypothesis building toward an understanding of genes and pathway responses driven by environments. Methods designed to estimate and analyze gene expression, with regard to treatments or conditions, can be leveraged to understand gene-level responses in the cell. However, genes often interact and signal within larger structures such as pathways and networks. Complex studies guided toward describing dynamic genetic pathways and networks require algorithms or methods designed for inference based on gene interactions and related topologies. Classes of algorithms and methods may be integrated into generalized workflows for comparative genomics studies, as multi -omics …

Screening For Potential Therapeutic Targets Of Yb-1 Protein Using A Bioinformatics Approach, Omar Muneer Karkoutly

Theses and Dissertations

Treatment options for cancer are becoming much more limited due to the robust characteristics of cancer that allows them to rapidly develop drug resistance. This may be a result of cancer cells’ ability to switch between differentiated and undifferentiated states (plasticity). Diagnostic measurement and detection of cancer and its progression is essential for developing successful treatments. Specific cancer targets whose expressions are highly associated with increased incidence, risk, and spread of cancer therefore become perfect targets for therapeutic intervention. One such novel target that is still being studied is the Y-box binding protein 1 (YB-1), which …

Bioinformatic Pipeline For Determining Terminal Repeats In The Human Cytomegalovirus Genome Assembled With Pacbio Long Read Sequences, Ahmed Al Qaffas

Theses and Dissertations

Human Cytomegalovirus (HCMV) is a member of the betaherpesvirinae subfamily of the Herpesvirus family. HCMV infection is common among adults worldwide, with an estimated seroprevalence of 66 to 95%, depending on the geographic region (Zuhair et al., 2019). Although most of the virus genomic content has been studied extensively, the terminal repeating region sequences remain understudied. Two main challenges hindered the study of the region: a) limitations of sequencing technologies; and b) misassembly of the repeats due to its complex nature. Here I show a novel bioinformatics pipeline that takes advantage of PacBio's long reads to resolve the challenges mentioned …

Microbial Communities Hosted By Carnivorous Pitcher Plants: Diversity, Recruitment, Functions And Succession In Sarracenia Purpurea Microbiomes, Jacob Jeffrey Grothjan

Theses and Dissertations

The pitcher plant Sarracenia purpurea supplements nutrient acquisition through carnivory, capturing insect prey which are digested by a food web community of eukaryotes and bacteria. Analysis of both bacterial and eukaryotic diversity, and an understanding of bacterial recruitment into pitchers and succession of bacterial and eukaryotic communities over time have not been well explored. This thesis presents three studies designed to address these gaps using field sampling and manipulative greenhouse experiments. Study I compared bacterial and eukaryotic composition and diversity of pitcher communities within and between populations of plants in two distinct wetland habitats. Genetic sequence analysis revealed an underappreciated …

Utilization Of Bioinformatic And Next Generation Sequencing Approaches For The Discovery Of Predictive Biomarkers And Molecular Pathways Involved In Bovine Respiratory Disease, Matthew Adam Scott

Theses and Dissertations

Bovine respiratory disease (BRD) is a highly dynamic disease complex that results from host, microbial agent, and environmental interactions. Despite nearly a century of targeted research, BRD remains the most economically damaging disease in beef cattle production and appears to be increasing in global incidence. While modern modalities for BRD detection exist, clinical diagnosis and management decisions largely depend upon clinical observations and their associated risk of disease. Though these approaches lack precision, they remain in use for many reasons, including fiscal and time constraints within beef production systems. Advancements in high-throughput sequencing have demonstrated the ability to provide insight …

Mucinomics: A Bioinformatic Analysis Of Snail Mucins, And Their Function, Maxwell B. Mcdermott

Theses and Dissertations

This thesis outlines the current research on secreted snail mucus, highlighting the potential of this biopolymer, and also demonstrates a research strategy to fulfill the unmet need of examining the hierarchical structures that lead to the enormous biological and chemical diversity of snail mucus genes.

Computational Analysis And Prediction Of Intrinsic Disorder And Intrinsic Disorder Functions In Proteins, Akila I. Katuwawala

Theses and Dissertations

COMPUTATIONAL ANALYSIS AND PREDICTION OF INTRINSIC DISORDER AND INTRINSIC DISORDER FUNCTIONS IN PROTEINS

By Akila Imesha Katuwawala

A dissertation submitted in partial fulfillment of the requirements for the degree of Engineering, Doctor of Philosophy with a concentration in Computer Science at Virginia Commonwealth University.

Virginia Commonwealth University, 2021

Director: Lukasz Kurgan, Professor, Department of Computer Science

Proteins, as a fundamental class of biomolecules, have been studied from various perspectives over the past two centuries. The traditional notion is that proteins require fixed and stable three-dimensional structures to carry out biological functions. However, there is mounting evidence regarding a “special” class …

Antimicrobial Peptide Development: From Massively Parallel Peptide Sequencing To Bioinformatic Motif Identification, Alexander K. Erikson

Theses and Dissertations

The isolation, purification, and clinical deployment of antibiotics is one of the major drivers of decrease in morbidity and mortality from infectious bacteria in the 20th century. The rapid, ubiquitous deployment of antibiotics encouraged swift development and distribution of antibiotic resistance. New, novel techniques, technologies, and ultimately therapeutic antimicrobial compounds will be required to counter the rise of antibiotic resistant microbes. Historically, mimicking naturally occurring compounds has been the most fruitful method for discovering new antibiotics; unsurprisingly, many recent efforts have focused on expanding the cultivation and detection of previously unknown microbes and compounds, respectively. Other techniques explore developing compounds …

Bioinformatic Analysis Of Venom Proteins From Dasymutilla Occidentalis, Eva Gunawan

Theses and Dissertations

Venom proteins have been found in a wide range of species in the animal kingdom. These venoms serve various functions such as defense against predators, hunting for food, and parasitism for reproduction. Because of their diverse functions, venom proteins are utilized in agrochemical treatments for protection from pests as well as treatments to control human diseases. Venoms, including those coming from a range of insect species, have been manipulated for these purposes, but many remain uncharacterized. Currently, one of the orders that venom-based research is focusing on are parasitoids from the order Hymenoptera. The purpose of some venom proteins in …

A Molecular And Bioinformatic Investigation Into The Phylogenetic Relationships And Life Cycles Of Amoeboid Protists, Alexander K. Tice

Theses and Dissertations

Eukaryotic organisms that cannot be classified as animals, land plants, or fungi are termed protists. Despite the fact that protists represent the majority of eukaryotic diversity, these organisms have received relatively little attention from biological researchers beyond morphological characterization. Reasons that likely contributed to their neglect include their mostly microscopic nature, that only a few lineages are the causative agents of human disease, that laboratory cultivation can be challenging, and that species concepts for the majority of protists was vague in many lineages. Initial attempts to resolve relationships among eukaryotes produced the five kingdoms model. This model suggested protists were …

Metagenomic Sequencing, Microbiome Reconstruction, And Analysis Of Ancient North And Central American Dental Calculus, Jonathan Belanich

Theses and Dissertations

Analyses of human oral microbiomes reveal substantial amounts of information about health, diet, and diseases of individuals and their communities within the archaeological record. In order to examine bacterial genomes from the past, specific archaeological samples that contain remnants of the microbial communities in question must be utilized. Recent developments in high-throughput, next-generation DNA sequencing have enabled the characterization of entire oral microbiomes and genomes from the remains of the bacteria trapped in calcified dental plaque. This project analyzed samples of ancient human dental calculus from North and Central America, which were examined for the changes within the oral microbiome …

Role Of Clic4 And The Synaptic Transcriptome In The Behavioral And Molecular Neurobiology Of Ethanol, Rory M. Weston

Theses and Dissertations

Alcohol use disorder (AUD) is a prevalent neuropsychiatric disease with profound health, social, and economic consequences. With an estimated 50% heritability, identifying genes that engender risk and contribute to the underlying neurobiological mechanisms represents an important first step in developing effective treatments. Gene expression studies are an important source of candidate genes for studying AUD, providing windows into the molecular machinery engaged by the brain in response to ethanol. Published studies have identified chloride intracellular channel 4 (Clic4) as an ethanol-regulated gene in brain capable of modulating sensitivity to sedation in multiple species. The functions of Clic4 are …

Genetics And Morphology Of Invasive Tubastraea Species Within The Gulf Of Mexico: A Case Study Of Species Misidentification And Distribution, Amelia E. Mcclure

Theses and Dissertations

The invasive corals, Tubastraea coccinea and Tubastraea micrathus, are known to thrive in reefs within the Gulf of Mexico (GOM). Many studies have indicated that species within this genus are spreading throughout the western Atlantic due to their successful invasion on degraded and artificial reef systems. In the Northern GOM, artificial reefs have been created from decommissioned oil rigs and sunken vessels to provide a hard substrate for coral growth. Although, this method is demonstrating success, it is also facilitating, the dispersal of undesired species. The species, T. coccinea and T. micranthus, were thought to be the only …

Evaluating Predixcan’S Ability To Predict Differential Expression Between Alcoholics And Non-Alcoholics, John E. Drake Jr

Theses and Dissertations

PrediXcan is a recent software for the imputation of gene expression from genotype data alone. Using an overlapping set of transcriptome datasets from postmortem brain tissues of donors with alcohol use disorder and neurotypical controls, which were generated by two different platforms (e.g., Arraystar and Affymetrix), and an additional unrelated transcriptome dataset from lung tissue, we sought to evaluate PrediXcan’s ability to impute gene expression and identify differentially expressed genes. From the Arraystar platform, 1.3% of matched genes between the measured and imputed expression had a Pearson correlation ≥ 0.5. Our attempt to replicate this finding using the expression data …

Cultivating Ecosystems: Microbial Communities In Recirculating Aquaculture Systems, Ryan Bartelme

Theses and Dissertations

Intensive cultivation of fish is necessary to meet future global market demands. Recirculating aquaculture systems (RAS) enable dense growth of fish, while occupying less space than traditional aquaculture farms. However, RAS often experience complications and high fish mortalities due to disease and improper waste management. In properly functioning systems, the microorganisms associated with fish (gut, scales) as well as those found in the system environment (water, component surfaces) remove waste and maintain fish health by discouraging growth of opportunistic pathogens. Previous RAS microbiome studies are small in scope, utilize coarse methods, and contain limited long-term spatial or temporal data. With …

Mining The Red Sea Metagenomics Libraries For Betaine Pathways, Sherouk Allam

Theses and Dissertations

Glycine Betaine (GB) is a fundamental solute for salinity tolerance in many organisms. Our aim in this study was to identify the GB pathway in highly complex natural community inhabiting brine pool and Red Sea column in Atlantis II Red Sea. Environmental genomics is a powerful tool for collecting information on microbial communities. Knowledge can be collected about highly complex natural communities. Microbial community living in extreme conditions evolved divers molecular mechanisms to withstand these conditions. Metagenomic libraries from Atlantic II samples were used to study betaine biosynthetic pathway that is more abundant. Betaine is synthesized independently from two different …

Discovering Driver Mutations In Biological Data, Yahya Bokhari

Theses and Dissertations

Background

Somatic mutations accumulate in human cells throughout life. Some may have no adverse consequences, but some of them may lead to cancer. A cancer genome is typically unstable, and thus more mutations can accumulate in the DNA of cancer cells. An ongoing problem is to figure out which mutations are drivers - play a role in oncogenesis, and which are passengers - do not play a role. One way of addressing this question is through inspection of somatic mutations in DNA of cancer samples from a cohort of patients and detection of patterns that differentiate driver from passenger mutations. …

Network Analytics For The Mirna Regulome And Mirna-Disease Interactions, Joseph Jayakar Nalluri

Theses and Dissertations

miRNAs are non-coding RNAs of approx. 22 nucleotides in length that inhibit gene expression at the post-transcriptional level. By virtue of this gene regulation mechanism, miRNAs play a critical role in several biological processes and patho-physiological conditions, including cancers. miRNA behavior is a result of a multi-level complex interaction network involving miRNA-mRNA, TF-miRNA-gene, and miRNA-chemical interactions; hence the precise patterns through which a miRNA regulates a certain disease(s) are still elusive. Herein, I have developed an integrative genomics methods/pipeline to (i) build a miRNA regulomics and data analytics repository, (ii) create/model these interactions into networks and use optimization techniques, motif …

A Framework For The Design And Analysis Of High-Performance Applications On Fpgas Using Partial Reconfiguration, Richard D. Anderson

Theses and Dissertations

The field-programmable gate array (FPGA) is a dynamically reconfigurable digital logic chip used to implement custom hardware. The large densities of modern FPGAs and the capability of the on-thely reconfiguration has made the FPGA a viable alternative to fixed logic hardware chips such as the ASIC. In high-performance computing, FPGAs are used as co-processors to speed up computationally intensive processes or as autonomous systems that realize a complete hardware application. However, due to the limited capacity of FPGA logic resources, denser FPGAs must be purchased if more logic resources are required to realize all the functions of a complex application. …

Genes, Transposable Elements, And Small Rnas: Studying The Evolution Of Diverse Genomic Components, Michael W. Vandewege

Theses and Dissertations

The evolution of genes and genomes has attracted great interest. The research presented here is an examination of genomes at three distinct levels, protein evolution, gene family evolution, and TE content regulation. First at a genetic level, I conducted an analysis of the salivary androgen-binding proteins (ABPs). I focused on comparing patterns of molecular evolution between the Abpa gene expressed in the submaxillary glands of species of New World and Old World muroids and found that in both sets of rodents, the Abpa gene expressed in the submaxillary glands appear to be evolving under sexual selection, suggesting ABP might play …

A Pipeline For Creation Of Genome-Scale Metabolic Reconstructions, Shaun W. Norris

Theses and Dissertations

The decreasing costs of next generation sequencing technologies and the increasing speeds at which they work have lead to an abundance of 'omic datasets. The need for tools and methods to analyze, annotate, and model these datasets to better understand biological systems is growing. Here we present a novel software pipeline to reconstruct the metabolic model of an organism in silico starting from its genome sequence and a novel compilation of biological databases to better serve the generation of metabolic models. We validate these methods using five Gardnerella vaginalis strains and compare the gene annotation results to NCBI and the …

Bioinformatics For The Comparative Genomic Analysis Of The Cotton (Gossypium) Polyploid Complex, Justin Thomas Page

Theses and Dissertations

Understanding the composition, evolution, and function of the cotton (Gossypium) genome is complicated by the joint presence of two genomes in its nucleus (AT and DT genomes). Specifically, read-mapping (a fundamental part of next-generation sequence analysis) cannot adequately differentiate reads as belonging to one genome or the other. These two genomes were derived from progenitor A-genome and D-genome diploids involved in ancestral allopolyploidization. To better understand the allopolyploid genome, we developed PolyCat to categorize reads according to their genome of origin based on homoeo-SNPs that differentiate the two genomes. We re-sequenced the genomes of extant diploid relatives of tetraploid cotton …

Feature Identification And Reduction For Improved Generalization Accuracy In Secondary-Structure Prediction Using Temporal Context Inputs In Machine-Learning Models, Matthew Benjamin Seeley

Theses and Dissertations

A protein's properties are influenced by both its amino-acid sequence and its three-dimensional conformation. Ascertaining a protein's sequence is relatively easy using modern techniques, but determining its conformation requires much more expensive and time-consuming techniques. Consequently, it would be useful to identify a method that can accurately predict a protein's secondary-structure conformation using only the protein's sequence data. This problem is not trivial, however, because identical amino-acid subsequences in different contexts sometimes have disparate secondary structures, while highly dissimilar amino-acid subsequences sometimes have identical secondary structures. We propose (1) to develop a set of metrics that facilitates better comparisons between …

Prediction Of Protein-Protein Interactions In Escherichia Coli From Experimental Data In Treponema Pallidum, Marco A. Abreu

Theses and Dissertations

Protein – Protein interactions (PPIs) are thought to be conserved between species, although this has not been systematically investigated. This problem was explored in Escherichia coli from experimental data in Treponema pallidum by predicting PPIs, focusing on protein domains of little or unknown function. The comparison of T. pallidum to a model organism such as E. coli can not only reveal additional data about T. pallidum but also reveals how E. coli is similar to this distantly related, obligate parasite. A set of novel T. pallidum interactions, enriched for proteins of unknown function, were the basis of over 23,000 predicted …

Bioinformatic Solutions To Complex Problems In Mass Spectrometry Based Analysis Of Biomolecules, Ryan M. Taylor

Theses and Dissertations

Biological research has benefitted greatly from the advent of omic methods. For many biomolecules, mass spectrometry (MS) methods are most widely employed due to the sensitivity which allows low quantities of sample and the speed which allows analysis of complex samples. Improvements in instrument and sample preparation techniques create opportunities for large scale experimentation. The complexity and volume of data produced by modern MS-omic instrumentation challenges biological interpretation, while the complexity of the instrumentation, sample noise, and complexity of data analysis present difficulties in maintaining and ensuring data quality, validity, and relevance. We present a corpus of tools which improves …

Inferring Gene Regulatory Networks From Expression Data Using Ensemble Methods, Janusz Slawek

Theses and Dissertations

High-throughput technologies for measuring gene expression made inferring of the genome-wide Gene Regulatory Networks an active field of research. Reverse-engineering of systems of transcriptional regulations became an important challenge in molecular and computational biology. Because such systems model dependencies between genes, they are important in understanding of cell behavior, and can potentially turn observed expression data into the new biological knowledge and practical applications. In this dissertation we introduce a set of algorithms, which infer networks of transcriptional regulations from variety of expression profiles with superior accuracy compared to the state-of-the-art techniques. The proposed methods make use of ensembles of …