Bioinformatics Commons^™

Molecular Mechanisms Of Opioid Use Disorder In Human Brain Models, Emily Mendez

Dissertations & Theses (Open Access)

Opioid use disorder (OUD) is a national and global public health crisis with no end in sight. While studies from animal models hint at widespread epigenetic and transcriptomic alterations of opioid drugs, the molecular consequences of long-term exposure to opioid drugs in human brain is still unclear, and human-centered translational models are necessary to discern the human cell type-specific effects of OUD.

Using postmortem brain Brodmann area 9 (BA9) from the UTHealth Brain Collection for Research on Psychiatric Disorders, I identified angiogenic gene networks perturbed in the RNA and protein of OUD subjects, as well as downregulation of many neuron-correlated …

Documenting The Southern Range Terminus Of The Wood Frog (Lithobates Sylvaticus) In North America, Christian Braswell

Theses

The Wood Frog (Lithobates sylvaticus) holds a remarkable position in North American amphibian biology, with its range extending from the Arctic Circle down to the near sub-tropical southeastern United States. This thesis presents a novel quantitative polymerase chain reaction analysis (qPCR) primer specific to L. sylvaticus and a survey effort regarding the southernmost distribution and detection of this species in Alabama through the application of environmental DNA (eDNA) sampling techniques. By investigating historical data and employing advanced genetic methodologies, this research provides insights into the contemporary status and distribution of the Wood Frog. This research is important to …

Integrative Genomic Insights Into Coral Resilience: Adaptive And Acclimatory Responses To Seasonal Environmental Shifts, Tasnim Ghanim

Theses and Dissertations

Coral reefs, critical to marine biodiversity and coastal protection, face escalating threats from climate change-related phenomena such as ocean warming. This warming is leading to widespread thermal stress that contributes to coral bleaching and infectious disease in corals, leading to the disruption of marine ecosystems and the economies that depend on them. Focusing on the brain coral Platygyra daedalea, known for its thermal resilience in the Persian Arabian Gulf—a region that exemplifies the extreme stressors of climate change—our study aims to dissect the genetic, transcriptomic, and microbiological underpinnings of coral survival in high-temperature environments predicted for the end of …

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 …

Elastin-Like Polypeptide As A Model To Study Intrinsically Disordered Proteins, Sadegh Majdi

Theses and Dissertations

The elastin-like polypeptide (ELP) is a well-studied structural protein that is easily amenable to amino acid (AA) sequence modifications and has the potential to yield a wide variety of uses in bioengineering and biomedical applications. One unique property of ELP is the inclusion of intrinsically disordered domains (IDP) within the structure that allow for its diversity of physical properties. While it is generally understood that amino acid sequence dictates protein folding arrangements, the contributions of specific amino acid sequences to the intrinsic disorder of ELP has yet to be fully resolved. Therefore, identifying the contributions of specific amino acid sequences …

Molecular Understanding And Design Of Deep Eutectic Solvents And Proteins Using Computer Simulations And Machine Learning, Usman Lame Abbas

Theses and Dissertations--Chemical and Materials Engineering

Hydrophobic deep eutectic solvents (DESs) have emerged as excellent extractants. A major challenge is the lack of an efficient tool to discover DES candidates. Currently, the search relies heavily on the researchers’ intuition or a trial-and-error process, which leads to a low success rate or bypassing of promising candidates. DES performance depends on the heterogeneous hydrogen bond environment formed by multiple hydrogen bond donors and acceptors. Understanding this heterogeneous hydrogen bond environment can help develop principles for designing high performance DESs for extraction and other separation applications. This work investigates the structure and dynamics of hydrogen bonds in hydrophobic DESs …

Model-Based Deep Autoencoders For Clustering Single-Cell Rna Sequencing Data With Side Information, Xiang Lin

Dissertations

Clustering analysis has been conducted extensively in single-cell RNA sequencing (scRNA-seq) studies. scRNA-seq can profile tens of thousands of genes' activities within a single cell. Thousands or tens of thousands of cells can be captured simultaneously in a typical scRNA-seq experiment. Biologists would like to cluster these cells for exploring and elucidating cell types or subtypes. Numerous methods have been designed for clustering scRNA-seq data. Yet, single-cell technologies develop so fast in the past few years that those existing methods do not catch up with these rapid changes and fail to fully fulfil their potential. For instance, besides profiling transcription …

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Investigating The Impact Of Transcription On Mutation Rates, Sarah Patterson

Theses and Dissertations

tRNA genes are highly transcribed and perform one of the most fundamental cellular functions. Although a universal pattern observed across all three domains of life is that highly transcribed genes tend to evolve slowly, tRNA genes have been shown previously to evolve rapidly. This rapid sequence evolution could result from relaxed selection, increased mutation rate, or a combination of both. Here, we use mutation-accumulation line sequencing data to show that tRNA genes accumulate more mutations than other gene types. Our results indicate that this elevated mutation rate is a consequence of both elevated transcription-associated mutagenesis and a lack of transcription-coupled …

Flavonol Glucosylation: A Structural Investigation Of The Flavonol Specific 3-O Glucosyltransferase Cp3gt, Aaron S. Birchfield

Electronic Theses and Dissertations

Flavonoid glycosyltransferases (GTs), enzymes integral to plant ecological responses and human pharmacology, necessitate rigorous structural elucidation to decipher their mechanistic function and substrate specificity, particularly given their role in the biotransformation of diverse pharmacological agents and natural products. This investigation delved into a comprehensive exploration of the flavonol 3-O GT from Citrus paradisi (Cp3GT), scrutinizing the impact of a c-terminal c-myc/6x histidine tag on its enzymatic activity and substrate specificity, and successfully achieving its purification to apparent homogeneity. This established a strong foundation for potential future crystallographic and other structure/function analyses. Through the strategic implementation of site-directed mutagenesis, a thrombin …

Exploring Soil Microbial Dynamics In Southern Appalachian Forests: A Systems Biology Approach To Prescribed Fire Impacts, Saad Abd Ar Rafie

Doctoral Dissertations

Prescribed fires in Southern Appalachian forests are vital in ecosystem management and wildfire risk mitigation. However, understanding the intricate dynamics between these fires, soil microbial communities, and overall ecosystem health remains challenging. This dissertation addresses this knowledge gap by exploring selected aspects of this complex relationship across three interconnected chapters.

The first chapter investigates the immediate effects of prescribed fires on soil microbial communities. It reveals subtle shifts in porewater chemistry and significant increases in microbial species richness. These findings offer valuable insights into the interplay between soil properties and microbial responses during the early stages following a prescribed fire. …

Regulation Of Protein Synthesis In Arabidopsis Thaliana Through A Bioinformatic And Mathematical Lens, Ricardo Andres Urquidi Camacho

Doctoral Dissertations

Organisms exist under constantly varying environmental and internal conditions, which necessitate the differential regulation of gene expression. To synthesize proteins, the ribosome translates the information encoded in the nucleotide sequence of an mRNA into the final, functional amino acid sequence. Knockouts of ribosomal proteins lead to lethality. One such protein is the ribosomal protein 6 of the small subunit (eS6/RPS6). We confirmed that the knockout of either one of two eS6 paralogs in Arabidopsis leads to stunted growth and chlorosis. Here, these phenotypes have been further characterized in seedlings by precisely quantifying the ribosome loading of mRNAs as well as …

A Cancer-Specific Study On The Differentially Expressed Protein-Protein Interactions Of Fumarate Hydratase, Sydney Lac

Dissertations & Theses (Open Access)

Fumarate hydratase (FH) is an enzyme used in the Krebs Cycle to convert fumarate to malate, and it is controlled by the FH gene. In this paper, we will investigate its role in Uterine Corpus Endometrial Carcinoma (UCEC) and how FH-deficient cells affect tumorigenesis. It is well-established that FH has been extensively studied in connection with renal cell carcinoma, skin and uterine leiomyomas, pheochromocytoma, and paraganglioma. However, we aim to construct an interaction network of significant genes related to the FH gene under conditions of FH deficiency in the Kreb Cycle. Creating an interactive network that illustrates the interconnectedness of …

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 …

Computational Molecular Docking Studies Of Small Molecule Inhibitors With The Sars-Cov-2 Spike Protein Variants: In-Silico Drug Discovery Using Virtual Screening And Drug Repurposing Approaches, Grace Gupta

Computational and Data Sciences (MS) Theses

The pandemic caused by the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has caused a global public health crisis of nearly unprecedented scale. In the years following the outbreak, the scientific community has mobilized to develop several vaccines and treatments. Drug repurposing as a strategy for drug development has produced many of the current therapeutic options. The greatest challenge to designing a therapeutic inhibitor of SARS-CoV-2 is the shifting mutational landscape of the virus as it evolves. In this study, we focus on the spike protein as a target for potential inhibitors. We explore two …

Interpretable Mechanistic And Machine Learning Models For Pre-Dicting Cardiac Remodeling From Biochemical And Biomechanical Features, Anamul Haque

All Dissertations

Biochemical and biomechanical signals drive cardiac remodeling, resulting in altered heart physiology and the precursor for several cardiac diseases, the leading cause of death for most racial groups in the USA. Reversing cardiac remodeling requires medication and device-assisted treatment such as Cardiac Resynchronization Therapy (CRT), but current interventions produce highly variable responses from patient to patient. Mechanistic modeling and Machine learning (ML) approaches have the functionality to aid diagnosis and therapy selection using various input features. Moreover, 'Interpretable' machine learning methods have helped make machine learning models fairer and more suited for clinical application. The overarching objective of this doctoral …

Novel Microbial Guilds Implicated In N2o Reduction, Guang He

Doctoral Dissertations

N₂O is a long-recognized greenhouse gas (GHG) with potential in global warming and ozone depletion. Terrestrial ecosystems are a major source of N₂O due to imbalanced N₂O production and consumption. Soil pH is a chief modulating factor controlling net N₂O emissions, and N₂O consumption has been considered negligible under acidic conditions (pH <6). In this dissertation, we obtained solids-free cultures reducing N₂O at pH 4.5. Furthermore, a co-culture (designated culture EV) comprising two interacting bacterial population was acquired via consecutive transfer in mineral salt medium. Integrated phenotypic, metagenomic and metabolomic analysis dictated that the Serratia population excreted certain …

Determining The Effects Of Glycocalyx Modifications On The Electrophysical Properties Of Human Mesenchymal Stem Cells, Rominna E. Valentine Ico

Electronic Theses, Projects, and Dissertations

Human mesenchymal stem cells (hMSCs) have gained popularity in clinical trials due to their multipotent differentiation characteristics, ability to secrete bioactive molecules, migrate into diseased or damaged tissues, and their immunosuppressive properties. HMSC cultures are heterogeneous, containing stem cells, partially differentiated progenitor cells, and fully differentiated cells. One of the major challenges with hMSCs therapeutic potential is the inability to select specific cell subpopulations due to an insufficient number of biomarkers. Often the biomarkers used, like those for fluorescence-activated cell sorting, are not sufficient to define hMSCs because they overlap with other cell types. Consequently, there is a need to …

Identification Of Biomarkers Of Sub-Lethal Algal Toxin Exposure In Atlantic Salmon (Salmo Salar) And Chinook Salmon (Oncorhynchus Tshawytscha) Using Differential Gene Expression Analysis, Brandon Ellingson

Biology Theses

Atlantic Salmon (Salmo salar) and Chinook Salmon (Oncorhynchus tshawytscha) are important culturally, recreationally, economically, and are a common aquaculture species in Canada and the United States. In the Pacific Northwest, blooms of toxic algae result in millions of dollars annually in losses for salmonid aquaculture producers. Blooms of harmful cyanobacteria produce microcystins which have been linked to net-pen liver disease which has large financial impacts on net pen salmon operations. Microcystin-LR, the most toxic variant, bioaccumulates in the liver and disrupts normal cellular activity by inhibiting protein phosphatases leading to deleterious effects on growth, immune status, and liver function. To …

Coupling Chemical And Genomic Data Of Marine Sediment-Associated Bacteria For Metabolite Profiling, Stephanie P. Suarez

USF Tampa Graduate Theses and Dissertations

Marine sediment-associated bacteria house many new and exciting novel secondary metabolites. These metabolites can be tested for bioactivity against various types of cancer and fungal, bacterial, and viral infections. In this thesis, we investigated the combination of biosynthetic gene cluster information with mass spectra to perform a chemical profiling of sediment- associated bacteria. Furthermore, we utilized a scoring technique to provide an identification and confidence score to each annotated compound. The sediment was collected from east Arthur Harbor, Palmer Station, Antarctica, at depths of 20 ft and 60 ft. After plating on agar, 52 unique bacterial strains were isolated, with …

Tracing Evolution Of Gene Transfer Agents Using Comparative Genomics, Roman Kogay

Dartmouth College Ph.D Dissertations

The accumulating evidence suggest that viruses and their components can be domesticated by their hosts, equipping them with convenient molecular toolkits for various functions. One of such domesticated system is Gene Transfer Agents (GTAs) that are produced by some bacteria and archaea. GTAs morphologically resemble small phage-like particles and contain random fragments of their host genome. They are produced only by a small fraction of the microbial population and are released through a lysis of the host cell. Bioinformatic analyses suggest that GTAs are especially abundant in the taxonomic class of Alphaproteobacteria, where they are vertically inherited and evolve …

Biomechanical Adaptations While Performing Bilateral Drop Landings With A Unilateral Ankle Tape Application, Eric Daniel Jenkins

Rehabilitation Sciences Theses & Dissertations

Ankle sprains are the most common injury in sport and exercise performance, which makes the utilization of ankle taping a common procedure to both prevent potential sprain, as well as protect against reinjury. However, unilateral ankle taping may have unintended consequences on the mechanics of the ankle and other joints of both legs. The aim of this dissertation was to determine the effects of ankle taping on lower body kinetics and kinematics, stiffness, and coordination during a bilateral landing task.

Twelve female participants completed a total of 90 drop landings across two visits, randomized from landing platforms of 30, 45, …

Tracing And Segmentation Of Molecular Patterns In 3-Dimensional Cryo-Et/Em Density Maps Through Algorithmic Image Processing And Deep Learning-Based Techniques, Salim Sazzed

Computer Science Theses & Dissertations

Understanding the structures of biological macromolecules is highly important as they are closely associated with cellular functionalities. Comprehending the precise organization of actin filaments is crucial because they form the dynamic cytoskeleton, which offers structural support to cells and connects the cell’s interior with its surroundings. However, determining the precise organization of actin filaments is challenging due to the poor quality of cryo-electron tomography (cryo-ET) images, which suffer from low signal-to-noise (SNR) ratios and the presence of missing wedge, as well as diverse shape characteristics of actin filaments. To address these formidable challenges, the primary component of this dissertation focuses …

Drug Repurposing Using Gene Expression Data Mining, Yue Qiu

Dissertations, Theses, and Capstone Projects

The conventional drug discovery process that employs the "one disease, one target, one drug'' paradigm is expensive, time-consuming, and has a high rate of failure for multi-genic complex diseases. An alternative approach to drug discovery is to repurpose an existing drug that has been used to treat some medical conditions. Drug repurposing is considered a promising method due to its accelerated the process of drug discovery and lower overall cost and risk.

Drug-perturbed gene expression profiles are powerful phenotype readouts of biological systems, and they have been widely used in drug repurposing studies. However, the existing drug-perturbed gene expression datasets …

State-Of-The-Art Approaches For Sequencing, Assembling And Annotating Naphthenic Acid Degrading Bacterial Metagenomes, Henry H. Say

Electronic Thesis and Dissertation Repository

Naphthenic acids (NAs) are the main toxic component of oil refinery wastewater and require special processes to be removed. Harnessing bacterial biodegradation for NA removal has the potential to be effective, yet NA-degrading bacteria and pathways are poorly understood and uncharacterized. To improve our understanding of NA degradation, I characterize the metagenomes of novel NA-degrading bacterial communities seeded in NA-enriched granulated activated carbon (GAC) filters. I demonstrate methods that maximize the throughput of extraction, sequencing, and annotation of novel metagenomes - producing 72 MAGs and other 5432 circular contigs - 226 of which were putative phages. I also include state-of-the-art …

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 …

Genome-Scale Methylation Analysis In Blood And Tumor Identifies Immune Profile, Age Acceleration, And Dna Methylation Alterations Associated With Bladder Cancer Outcomes, Ji-Qing Chen

Dartmouth College Ph.D Dissertations

Bladder cancer patients receive frequent screening due to the high tumor recurrence rate (more than 60%). Nowadays, the conventional monitoring method relies on cystoscopy which is highly invasive and increases patient morbidity and burden to the health care system with frequent follow-up. As a result, it is urgent to explore novel markers related to the outcomes of bladder cancer. Immune profiles have been associated with cancer outcomes and may have the potential to be biomarkers for outcomes management. However, little work has been conducted to investigate the associations of immune cell profiles with bladder cancer outcomes. Here, I utilized the …

Growth Of Purple Sulfur Bacteria Allochromatium Vinosum On Solid Phase Metal Sulfides As Sulfur And Electron Sources, Hugo Alarcon

Open Access Theses & Dissertations

Purple sulfur bacteria (PSB) are photosynthetic microorganisms known for their vital roles in geochemical cycles, especially the sulfur cycle, within anoxic photic environments. PSB are also key contributors to the nitrogen, carbon, and oxygen cycles. This study focuses on the autotrophic growth of Allochromatium vinosum, a model strain of PSB, that utilize solid-phase metal sulfides (MS) as both sulfur and electron donors. Through characterizing the growth profiles of A. vinosum on pyrite (FeS2), nickel sulfide (NiS), and iron monosulfide (FeS) nanoparticles, respectively, and investigating the bacteria-MS interaction mechanisms, this work expands our current knowledge of the metabolic capabilities and flexibility …

Computational Analysis Of Antibody Binding Mechanisms To The Omicron Rbd Of Sars-Cov-2 Spike Protein: Identification Of Epitopes And Hotspots For Developing Effective Therapeutic Strategies, Mohammed Alshahrani

Computational and Data Sciences (PhD) Dissertations

The advent of the Omicron strain of SARS-CoV-2 has elicited apprehension regarding its potential influence on the effectiveness of current vaccines and antibody treatments. The present investigation involved the implementation of mutational scanning analyses to examine the impact of Omicron mutations on the binding affinity of four categories of antibodies that target the Omicron receptor binding domain (RBD) of the Spike protein. The study demonstrates that the Omicron variant harbors 23 unique mutations across the RBD regions I, II, III, and IV. Of these mutations, seven are shared between RBD regions I and II, while three are shared among RBD …