Digital Commons Network^™

The Expanding Marine Built Environment And Biofilm Formation Processes, Rachel Mugge

Dissertations

The marine built environment (i.e., places or things made or modified by humans) in the northern Gulf of Mexico is rapidly expanding and includes over 2,000 known historic shipwrecks, nearly 4,100 artificial reefs, and other built structures for natural resource extraction, marine aquaculture, renewable energy generation, munitions dumping areas, and commercial and recreational activities. While these structures have the potential to develop into artificial reefs, acting as biodiversity hotspots that provide food and shelter and facilitate organism transport, it is unclear how they affect biodiversity and ecosystem function in the marine environment. The success of artificial reefs to become ecosystems …

Gene Regulatory Context Of Honey Bee Worker Sterility, Rahul Choorakkat Unnikrishnan

Electronic Thesis and Dissertation Repository

Honey bee workers deactivate their ovaries and are functionally sterile when a queen is present in the colony. I adopt a bioinformatics approach to up-date a model transcriptional regulatory network (TRN) to study gene-regulatory processes that regulate fecundity in workers. On splitting the network, I obtained nine clusters and each cluster conformed to properties associated with real-world networks. Two of the nine clusters are enriched for 'sterility genes' and contained single well-connected hub genes (GB44769, ftz-f1). The genes in the two clusters were functionally enriched for nucleic acid binding (GO:0003676) and nucleotide binding (GO:0000166). I identified homologous genes for …

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 …

Vircy-Seq : A Protocol For Characterizing Viral Activity, Tyler James Dion

Legacy Theses & Dissertations (2009 - 2024)

The main purpose of pharmaceutical production is to produce safe effective medicine for patient use. In an effort to ensure patient safety constant surveillance for viruses takes place. The detection of a viral nucleic acid in a pharmaceutical production setting results in investigations to assess its infectious potential. This is an intensive, expensive process that entails many tests such as the observation of hemadsorption, cytopathic effects (CPE), and more. These tests are typically specific and only capture certain viruses, as factors like CPE can only be observed in some viral species. A new investigational method that is effective on all …

Accurate Simulation Of Reads And Improved Strategies For Abundance Estimation Supporting Reduced Representation Sequencing For Metagenomics, Ryan Kuster

Doctoral Dissertations

Next generation sequencing has impacted all areas of biology by providing affordable investigations into some of the most complex processes underpinning life. With its ubiquitous application, there is still benefit in considering the nuances of the technology and its downstream analysis. Sequencing libraries produced by fragmenting DNA with restriction enzyme digests limit the scope of sequencing to a reduced set of genomic loci, allowing for deeper sequencing of those regions at a reduced cost per sample. These sequencing libraries have been used to determine genetic markers within populations of closely related individuals due to their sensitivity and preservation within populations. …

Towards More Complete Metagenomic Analyses Through Circularized Genomes And Conjugative Elements, Benjamin R. Joris

Electronic Thesis and Dissertation Repository

Advancements in sequencing technologies have revolutionized biological sciences and led to the emergence of a number of fields of research. One such field of research is metagenomics, which is the study of the genomic content of complex communities of bacteria. The goal of this thesis was to contribute computational methodology that can maximize the data generated in these studies and to apply these protocols human and environmental metagenomic samples.

Standard metagenomic analyses include a step for binning of assembled contigs, which has previously been shown to exclude mobile genetic elements, and I demonstrated that this phenomenon extends to all conjugative …

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 …

Population Genetics Of Populus Trichocarpa For Targeted Breeding As A Biofuel Crop, Cai John

Doctoral Dissertations

Populus trichocarpa (poplar) is a woody species native to the western U.S. and Canada. As a fast-growing crop, it has been under investigation by the Department of Energy as a resource for liquid biofuel production. Having recently expanded the collection of poplar whole-genome sequences so that it spans the entire natural species range, we have the novel opportunity to study adaptive responses across this range. This work starts with an initial proof of concept study in a well-studied portion of the species range that has complete whole-genome sequences and RNA expression. The completeness of these data allow robust validation of …

Modeling Electrostatics In Molecular Biology And Its Relevance With Molecular Mechanisms Of Diseases, Mahesh Koirala

All Dissertations

Electrostatics plays an essential role in molecular biology. Modeling electrostatics in molecular biology is complicated due to the water phase, mobile ions, and irregularly shaped inhomogeneous biological macromolecules. This dissertation presents the popular DelPhi package that solves PBE and delivers the electrostatic potential distribution of biomolecules. We used the newly developed DelPhiForce steered Molecular Dynamics (DFMD) approach to model the binding of barstar to barnase and demonstrated that the first-principles method could also model the binding. This dissertation also reflects the use of existing computational approaches to model the effects of Single Amino Acid Variations (SAVs) to reveal molecular mechanisms …

The Roles Of Epithelial–Mesenchymal Plasticity In Tumor Heterogeneity, Metastasis, And Patient Survival In Breast Cancer, Meredith Septer Brown

Dartmouth College Ph.D Dissertations

The Epithelial-to-Mesenchymal transition, a critical cellular process in development, is frequently co-opted by solid tumors to promote invasion and metastasis. In particular, the hybrid or intermediate EMT state, possessing both epithelial and mesenchymal characteristics, is associated with increased cancer stemness and plasticity. Similarly, intra-tumoral heterogeneity in solid tumors, in particular breast cancer, is associated with poor prognosis, tumor growth, proliferation, drug resistance, and metastasis. We sought to understand the link between the generation of intra-tumoral heterogeneity and the intermediate EMT state and their impact on tumor progression and patient prognosis. As part of my thesis work, I developed a model …

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 …

Characterizing Endogenous Dicer Products To Unravel Novel Rnai Biogenesis Pathways, Jacob Oche Peter

Dissertations

ABSTRACT

RNA interference (RNAi) is a pervasive gene regulatory mechanism in eukaryotes based on the action of multiple classes of small RNA (sRNA). Exploiting RNAi pathways in non-model systems have great potential for creating potent RNAi technologies. Here, we accessed RNAi-mediated control of gene expression in the two-spotted spider mite, Tetranychus urticae (T. urticae) using engineered dsRNA designed to modulate the host RNAi pathway and increase RNAi efficacy. Analysis of Dicer (Dcr) generated fragments revealed how exogenous RNAs access the host RNAi pathway in this animal, opening avenues for designing RNAi technology for their control. Further, some organisms …

Specialized Named Entity Recognition For Breast Cancer Subtyping, Griffith Scheyer Hawblitzel

Master's Theses

The amount of data and analysis being published and archived in the biomedical research community is more than can feasibly be sifted through manually, which limits the information an individual or small group can synthesize and integrate into their own research. This presents an opportunity for using automated methods, including Natural Language Processing (NLP), to extract important information from text on various topics. Named Entity Recognition (NER), is one way to automate knowledge extraction of raw text. NER is defined as the task of identifying named entities from text using labels such as people, dates, locations, diseases, and proteins. There …

Transcriptional Analysis Of Maize Under Drought Stress And The Impact Of Plant Maturity, Oliver J. Oviedo

Biology ETDs

Climate change related drought is projected to harm maize production. Water use strategies can help mitigate the impact of drought on crop yield. However, little is known about maize metabolic response to drought at different developmental stages. To shed light on this, drought conditions were applied to maize at the six-leaf stage (V6), twelve leaf stage (V12), and tassel stage (VT). V6 and VT took eight days to achieve a low stomatal conductance threshold, but V12 took 16 days. Differential gene expression analysis of the transcriptome indicates that V6 showed the most response with 53 impacted metabolic pathways, many of …

Exploiting Chemogenetic And Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities, Medina Colic

Dissertations & Theses (Open Access)

The advent of CRISPR technology and its adaptation to the mammalian genome made whole-genome knockout screens possible directly in human cells. Gene knockout answers how essential that gene is for cell fitness and proliferation. Genes showing moderate to severe fitness defects are called essential genes and provide insights into disease-specific candidate therapeutic targets. Additionally, CRISPR offers other applications for genome editing. Two applications this dissertation is based on are 1) combination of gene knockout and drug treatment, which enables the identification of chemogenetic interactions, or gene mutations that enhance or suppress the activity of a drug, and 2) combinatorial editing, …

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations & Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Bioinformatics Analysis Of The Transcriptomic Profiles Of Duchenne Muscular Dystrophy Patients / Narrative Competence And Cognitive Mapping As A Culturally Sustaining Pedagogy In The Education Of Emergent Bilinguals, Bianca Gonzalez

Legacy Theses & Dissertations (2009 - 2024)

Duchenne Muscular Dystrophy (DMD) is a muscle-wasting disease that primarily affects boys characterized by loss of the dystrophin gene. Dystrophin is necessary for proper muscle growth, muscles that lack dystrophin are more prone to damage. In this thesis, a bioinformatics approach was used to evaluate the transcriptomic profiles of two datasets obtained from DMD patients. The two datasets were analyzed separately, as well as combined to identify differentially expressed genes. The first dataset, GSE6011, has 23 DMD samples and 14 controls. The second, GSE38417, consists of 16 DMD samples and six controls. Differential gene expression of both datasets combined found …

A Study Of Mutations In Sars-Cov-2 Genomes, Michael Andrew Welford

Graduate Research Theses & Dissertations

The COVID-19 pandemic caused by the SARS-Cov-2 virus has affected the lives of everyone around the world. There has been a rapid appearance of new variants. As the variants affected the efficacy of vaccines, it is important to study the mutations of the variants. A pipeline of tools, SARS-CoV-2 Analyzer, was created to study the mutations in the most mutated S-gene of SARS-Cov-2. Two batches of data were used in this study: all samples available at The National Center for Biotechnology Information (NCBI) were downloaded in September 2021 (before the emergence of the first omicron variant) and December 2021 (after …

Building A Learning Healthcare System: A Path To Optimizing Big Health Data To Inform Clinical Care Decisions, Danne Charlotte Emily Elbers

Graduate College Dissertations and Theses

The explosive growth of data and computing power of the last decades has had large impacts on a myriad of domains, not in the least on one of society’s most complex systems: healthcare. In this work, a version of the resulting Learning Healthcare System (LHS) is explored and elements of it have been implemented and are in use at the Department of Veterans’ Affairs today. After an overview of what a LHS is and what it could be once executed in its full form, the chapters will describe in detail some of the individual elements and how they address cogs …

Framework For The Evaluation Of Perturbations In The Systems Biology Landscape And Inter-Sample Similarity From Transcriptomic Datasets — A Digital Twin Perspective, Mariah Marie Hoffman

Dissertations and Theses

One approach to interrogating the complexities of human systems in their well-regulated and dysregulated states is through the use of digital twins. Digital twins are virtual representations of physical systems that are descriptive of an individual's state of health, an object fundamentally related to precision medicine. A key element for building a functional digital twin type for a disease or predicting the therapeutic efficacy of a potential treatment is harmonized, machine-parsable domain knowledge. Hypothesis-driven investigations are the gold standard for representing subsystems, but their results encompass a limited knowledge of the full biosystem. Multi-omics data is one rich source of …

Determining Haplotype Specific X Chromosome Inactivation State And Related Epigenetic Features In Female X-Linked Genes, Ariah Dawn Mackie

Cal Poly Humboldt theses and projects

Females with heterozygous X-linked mutations are prone to pseudo-haploinsufficiency because random X chromosome inactivation (XCI) silences one of their two X chromosomes. A prior study explored the theory that reactivating the silenced healthy allele could be a treatment for pseudo-haploinsufficient females. The next step was to evaluate this approach in a clinically relevant stem cell model of the rare neurological disease CDKL5 Deficiency Disorder (CDD). It was necessary to validate X-inactivation state with respect to CDKL5 allele expression in one of these models. We explored CDKL5 allele expression in two populations of CDD female patient-derived induced pluripotent stem cells (iPSCs) …

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 …