Genomics Commons^™

Creation Of A Digital Storage System For Genome Sequencing Metadata, Jacquelin W. Olexa

Undergraduate Theses, Professional Papers, and Capstone Artifacts

As the field of computational genomics continues to expand in both potential and application, it is now more imperative than ever to ensure that massive genetic sequencing datasets are properly stored in an accessible manner. This project sought to establish a practical, user-friendly, secure system for a genomics research lab (the Good Lab; thegoodlab.org) at the University of Montana. A MySQL database and connected web application was ruled the best configuration to maximize utility and accessibility for the lab’s researchers. Building the logical framework for the database, creating the server, and sourcing data occurred over several months. The dataset ranged …

The Influence Of Drd2 Polymorphism Exon 8 C/T (Rs6276) On Manifestations Of Delirium Tremens & Alcohol Withdrawal Seizures, Naomi Schneider

Honors Theses and Capstones

This study explores the correlation between the DRD2 Polymorphism exon 8 C/T (rs6276) and manifestations of delirium tremens (DT). DT is a condition that is clinically diagnosed utilizing two characteristic symptom manifestations: the presence of delirium and severe alcohol withdrawal. It is not entirely understood why DT can occur in some patients, but evidence has suggested that genetic predisposition can play a role. Utilizing the National Institutes of Health (NIH) All of Us Research database and performing a secondary analysis of existing genomic data, this candidate gene association study aims to determine the genotype frequencies within three cohorts: a healthy …

Functional Analyses Of The Polycomb-Group Genes In Sea Lamprey Embryos Undergoing Programmed Dna Loss, Cody Saraceno

Theses and Dissertations--Biology

During early embryonic development, the sea lamprey (Petromyzon marinus) undergoes programmatic elimination of DNA from somatic progenitor cells in a process termed programmed genome rearrangement (PGR). Eliminated DNA eventually becomes condensed into micronuclei, which are then physically degraded and permanently lost from the cell. Previous studies indicated that many of the genes eliminated during PGR have mammalian homologs that are bound by polycomb repressive complex (PRC) in embryonic stem cells. To test whether PRC components play a role in the faithful elimination of germline-specific sequences, we used a combination of CRISPR/Cas9 and lightsheet microscopy to investigate the impact …

Genomic Studies Of The Equine Bloodworm, Strongylus Vulgaris, Nichol Ripley

Theses and Dissertations--Veterinary Science

Strongylus vulgaris is the most pathogenic nematode parasite of grazing horses worldwide. This gastrointestinal parasitic nematode is in the family Strongylidae under the subfamily Strongylinae, or Strongylins. While the epidemiology, complete life cycle, and high pathogenicity of the fourth and fifth larval stages of S. vulgaris are well established, we understand very little about its biology. This parasite is renowned for its unique life cycle and capacity to cause arterial damage, leading to significant health and economic impacts for the equine industry. It also is the most intensively documented Strongylin; however, S. vulgaris has yet to gain drug resistance as …

Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang

Dartmouth College Ph.D Dissertations

The three-dimensional organization of the genome is fundamental in regulating gene expression and maintaining cellular function. This organization's complexities, influenced by epigenetic marks and chromatin remodeling complexes, are crucial for understanding genomic regulation. Among these, the SWI/SNF complexes are key, facilitating chromatin accessibility and regulating gene activity across cell types. The first part of my dissertation focuses on SWI/SNF complexes, exploring their role in chromatin remodeling and their impact on 3D genome architecture. Utilizing next-generation sequencing (NGS) techniques, this section investigates the interplay between these complexes and chromatin structure. During my research on the SWI/SNF complex, I was intrigued by …

A Multimolecular Perspective On The Success Of Wolf Recovery And Relocation, Samuel D. Hervey

Dissertations, Master's Theses and Master's Reports

With global biodiversity in decline and many species isolated in fragmented habitats, conservation efforts increasingly rely on natural recolonization and translocation to restore ecosystems. These strategies face challenges such as genetic erosion and habitat limitations, highlighting the need for effective monitoring practices. This research assesses the success of wolf recovery initiatives by examining long-term genetic and genomic health using both traditional and advanced molecular methods. First, we investigated the genetic health of 19 gray wolves (Canis lupus) relocated to Isle Royale National Park to restore ecosystem balance. Initial genetic assessments with microsatellites found that these wolves had genetic diversity metrics …

Personalized Molecular Therapies For Advanced Non-Small Cell Lung Cancer: Overcoming Heterogeneity To Optimize Treatment Response And Clinical Outcomes, Zuan-Fu Lim

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer remains one of the deadliest cancers. Novel, paradigm shifting treatments including immunotherapy and targeted therapies have recently been developed to cull the deadly effects of lung cancer, but many challenges remain. There remains a significant unmet need to accurately predict and optimally select for patients who will respond to immune checkpoint inhibitors (ICI) treatment. In Chapter 2 of this dissertation, we investigated a novel live single cell cytokine profiling lab-on-chip platform, IsoLight, using peripheral CD4+ and CD8+ T-cells for ICI biomarker development. A total of 55,175 single T-lymphocytes were analyzed in this proof-of-concept study. We found that an …

Biology And Ecology Of Neonectria Magnoliae And Neonectria Punicea, Two Understudied Neonectria Species In West Virginia, Hannah Marie Petronek

Graduate Theses, Dissertations, and Problem Reports (ETD)

The family Nectriaceae includes numerous phytopathogenic fungi that cause canker diseases on both angiosperm and conifer hosts worldwide. Numerous Neonectria spp. cause cankers on hardwoods and conifers in North America, but their roles in contributing to tree decline and mortality outside of beech bark disease are largely understudied. One such pathogen, Neonectria magnoliae, causes perennial cankers on two native hosts in central Appalachia: Fraser magnolia (Magnolia fraseri) and tulip-poplar (Liriodendron tulipifera). We also recently confirmed N. magnoliae from non-native star magnolia (Magnolia stellata) in West Virginia. Both native hosts occur in the central …

The Influence Of Genes On The Migratory Timing Of Great Reed Warblers, Emily Fackler

Honors Undergraduate Theses

Many organisms migrate; however, there is a lack of knowledge on the mechanisms that drive migration timing, including which genes play a role. The great reed warbler (Acrocephalus arundinaceus), a migratory bird that breeds in Eurasia and overwinters in sub-Saharan Africa, is an excellent model to study the genetics of migration. Each season, some individuals migrate early, whereas others migrate later in the season. In other words, they exhibit differences in their migratory chronotypes. Past research has identified three candidate genes (TOP1, PEAK1, and CPNE4) that influence the migratory chronotypes of another avian species, …

The Evolution Of The Metazoan Circadian Molecular Mechanism And The Conservation Of Canonical Circadian Elements, Olivia Waldridge

Theses and Dissertations--Biology

The temporal organization of biological activities through circadian rhythms is pivotal for the survival of organisms. Significant progress has been made in understanding the molecular foundations of animal circadian clocks through the characterization of key components such as Clock, Bmal1/Cycle(Cyc), Period (Per), Timeless, and Cryptochrome (Cry) in several model organisms. To determine the universality of this conservation, we investigated the sequences of these genes and their paralogs across 46 animal species that encompass multiple phyla in the metazoan kingdom to resolve the relative timing of duplication and loss events that have diversified core clock components in the metazoan kingdom. Using …

Reproductive Isolation And Gene Flow Across Space, Time And Genomes In Neodiprion Lecontei And N. Pinetum, Ashleigh Nicole Glover

Theses and Dissertations--Biology

To explain biodiversity, evolutionary biologists must understand how independent lineages arise via the evolution of reproductive isolation during the speciation process. Hybridizing taxa provide an excellent opportunity to investigate the evolution of reproductive isolating barriers and genomic divergence, thereby enhancing our understanding of speciation. However, hybridization between diverging taxa can vary across geographic space, the genome, and time. Thus, understanding the factors that promote or inhibit hybridization can provide insight into the biotic, environmental, and genetic causes of divergence and gene flow. Importantly, the mechanisms responsible for generating variation in hybridization dynamics and the consequences of such hybridization remains unknown …

From Code To Crops: Harnessing Bioinformatics And Artificial Intelligence (Ai) In Agricultural Omics, Lakshay Anand

Theses and Dissertations--Plant and Soil Sciences

Global agricultural faces numerous challenges, such as climate change, resource limitations, novel pests and diseases, increasing costs, and the ever-increasing human population. To tackle these challenges, we need innovative strategies that combine new technologies and data analytics approaches to enhance agricultural output, promote sustainable methods, and optimize resource allocation. The key to this innovation lies in understanding the complex molecular web within plants that governs their growth, defense, and adaptability mechanisms. By mastering this molecular network, we can cultivate crops that are more resilient, sustainable, and suitable for different climatic terrains. Moreover, studying the symbiotic relationship between plants and microorganisms …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D'Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well-studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: Von Hippel-Landau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C (KDM5C). …

Developing Cellular Systems To Elucidate Rna Structural Dynamics Of Cag Expansion Transcripts In Spinocerebellar Ataxias, Victoria Demeo

Electronic Theses & Dissertations (2024 - present)

Spinocerebellar ataxias (SCAs) are a diverse group of over 40 genetically heterogeneous neurodegenerative disorders, many of which are caused by a trinucleotide CAG repeat expansion in the coding region of specific genes. These expansions lead to the production of polyglutamine (polyQ) tracts that interfere with normal protein function, triggering cellular dysfunction and contributing to disease pathogenesis. The most well-known of these SCAs, such as SCA1, SCA2, and SCA3, exhibit progressive neurodegeneration, yet the precise mechanisms through which these mutations cause disease remain poorly understood.

A significant challenge in studying CAG repeat expansion disorders lies in the complexity of the disease …

Refining The Scope Of Genetic Influences On Alcohol Misuse Through Environmental Stratification And Gene-Environment Interaction, Jeanne E. Savage, Christiaan A. De Leeuw, Josefin Werme, Spit For Science Working Group, Danielle M. Dick, Danielle Posthuma, Sophie Van Der Sluis

Psychology Faculty Publications

Background

Gene-environment interaction (G X E) is likely an important influence shaping individual differences in alcohol misuse (AM), yet it has not been extensively studied in molecular genetic research. In this study, we use a series of genome-wide gene-environment interaction (GWEIS) and in silico annotation methods with the aim of improving gene identification and biological understanding of AM.

Methods

We carried out GWEIS for four AM phenotypes in the large UK Biobank sample (N = 360,314), with trauma exposure and socioeconomic status (SES) as moderators of the genetic effects. Exploratory analyses compared stratified genome-wide association (GWAS) and GWEIS modeling approaches. …

Chromatin Regulation By Swi/Snf Remodelers In Somatic Stem Cell Maintenance And Transformation, Luke Thomas Deary

Dartmouth College Ph.D Dissertations

Cell identity is defined by the epigenome, whereby chromatin regulators work in concert to promote gene expression programs that serve a cell’s specialized purpose. Mutations in chromatin regulators are amongst the most frequent drivers of human disease, underscoring the importance of understanding their activities in maintaining cell identity and tissue function. In particular, mutations in subunits of the evolutionarily conserved SWI/SNF chromatin remodeling complexes drive diseases across human tissues in both development and adult tissue maintenance5. Three major SWI/SNF complexes exist: BAF, PBAF, and GBAF, which differ in their composition and genomic targeting but share an ATP-dependent catalytic activity to …

Genetic And Transcriptomic Investigations Of Progressive Ethanol Consumption In The Diversity Outbred Mouse, Zachary Tatom

Theses and Dissertations

As a complex genetic disorder, alcohol use disorder (AUD) is thought to be influenced by many genes each contributing only a small effect to the overall disease liability. Dozens of genes have been implicated as potentially affecting risk for AUD and alcohol consumption. However, understanding the full genetic architecture of AUD – what genes are involved, to what extent, and how these genes are regulated – remains a challenging step in identifying novel treatments. Gene expression studies in humans have attempted to augment GWAS of alcohol consumption but are often confounded by environmental factors; the difficulty of collecting tissue from …

Chemical Synthesis Of Sensitive Dna, Komal Chillar

Dissertations, Master's Theses and Master's Reports

Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …

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 …