Genomics Commons^™

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.

What I Talk About When I Talk About Integration Of Single-Cell Data, Yang Xu

Doctoral Dissertations

Over the past decade, single-cell technologies evolved from profiling hundreds of cells to millions of cells, and emerged from a single modality of data to cover multiple views at single-cell resolution, including genome, epigenome, transcriptome, and so on. With advance of these single-cell technologies, the booming of multimodal single-cell data creates a valuable resource for us to understand cellular heterogeneity and molecular mechanism at a comprehensive level. However, the large-scale multimodal single-cell data also presents a huge computational challenge for insightful integrative analysis. Here, I will lay out problems in data integration that single-cell research community is interested in and …

Genome Evolution In The Salicaceae: Genetic Novelty, Horizontal Gene Transfer, And Comparative Genomics, Timothy Yates

Doctoral Dissertations

Genome evolution is a powerful force which shapes genomes over time through processes like mutation, horizontal transfer, and sexual reproduction. Although questions which aim to explore genome evolution are broad, they are all understood through the discovery and comparison of genetic variation. For example, genetic diversity may explain differences in phenotypes, etiology of disease, and is essential for phylogenomic analysis. Recently, the democratization of next generation and third generation DNA sequencing technologies have allowed for genomics to produce large amounts of sequence data. This has facilitated the capture of genetic variation at species and population scales.

Populus and Salix are …

Mechanisms By Which Xenorhabdus Nematophila Interacts With Hosts Using Integrated -Omics Approaches, Nicholas C. Mucci

Doctoral Dissertations

Nearly all organisms exist in proximity to microbes. These microbes perform most of the essential metabolic processes necessary for homeostasis, forming the nearly hidden support system of Earth. Microbial symbiosis, which is defined as the long-term physical association between host and microbes, relies on communication between the microbial community and their host organism. These interactions among higher order organisms (such as animals, plants, and fungi) and their bacteria links metabolic processes between interkingdom consortia. Many questions on microbial behavior within a host remain poorly understood, such as the colonization efficiency among different microbial species, or how environmental context changes their …

Multi-Omic Systems Biological Analysis Of Host-Microbe Interactions, Piet Jones

Doctoral Dissertations

Systems biology offers the opportunity to understand the complex mechanisms of various biological phenomena. The wealth of data that is produced, at an increasing rate, provides the potential to meet this opportunity. Here we take an applied approach to integrate multiple omic level data sources in order to generate biologically relevant hypotheses. We apply a novel analysis pipeline to model both, in concert, the microbial and transcriptomic signature from COVID-19 positive patients. We show patients may suffer from an increased microbial burden, with an increased pathogen potential. Gene expression evidence further shows patients may exhibit a compromised barrier immunity, owing …

A Tissue Specific Transcriptomic, Proteomic And Phospho-Proteomic Atlas Of The Translational Machinery Of Arabidopsis Thaliana, Abdullah Salim

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Gene expression encompasses the flow of genetic information from DNA to mRNA (transcription) and from mRNA to protein (translation) along with the regulatory mechanisms underlying these processes. Omics technologies offer a powerful toolset with which to study gene expression at each of these stages. A recently published dataset integrating transcriptomic, proteomic and phospho-proteomic measurements from 30 Arabidopsis thaliana tissues provides a unique resource to explore gene expression.¹ The translational machinery (the ribosome, and its initiation, elongation, and termination factors) are a core component in gene expression. Defects in translation can be lethal or lead to major developmental defects and …

Applications Of Comparative Genomics And Data Science To Agricultural And Clinical Research, Katrina A. Schlum

Doctoral Dissertations

The advent of inexpensive, high-throughput whole genome sequencing (WGS) technologies has led to the generation of thousands of related genomes, even from a single study. Large-scale genome analysis has resulted in hypothesis-generating approaches in the fields of clinical, human and agriculture genomics. Additionally, population-level genomic sampling has resulted in a decrease in false positives in genotype-phenotype associations and an increase in understanding of the basis of disease, antibiotic and pesticide resistance. Deeper understanding of migration, genetic divergence and evolution has also been made possible due to WGS. This research applies comparative genomics, population genomics and data science approaches to whole …

The Effect Of Nuclear Perturbations On The 3d Organization Of The Genome, Rosela Golloshi

Doctoral Dissertations

Cells in our body experience constant mechanical forces that influence biological functions such as growth and development. The nucleus has been implicated as a key mechanosensor and can directly influence chromatin organization and epigenetic alterations leading to gene expression changes. However, the mechanism by which such mechanical forces lead to genomic alterations and expression of mechanosensitive genes is not fully understood. The work presented in this dissertation investigates the effect of mechanical and epigenetic perturbations on the 3D genome organization. To investigate this 3D genome folding, we use Chromosome Conformation Capture followed by high throughput sequencing (Hi-C) (Chapter-1) which identifies …

3d Genome Architecture Under Stress: A Survey Of Ionizing Radiation, Progeria, And Osmotic Stress, Jacob Tyler Sanders

Doctoral Dissertations

The human nucleus contains 2 meters of DNA which is intricately folded into a three-dimensional (3D) structure. It has become increasingly clear that this 3D structure plays an important role in the expression of genes. Proper gene expression is necessary for cellular homeostasis, cell state, and response to environmental/physical perturbations. Faithful repair of damage DNA damage is necessary to prevent genomic aberrations, such as translocations, which may lead to misregulation of gene expression. Hi-C, a sequencing technique that labels proximal chromatin interactions, provides a clearer picture of how the genome is spatially organized within the nucleus. Here, we discuss the …

Carbon Metabolism In Cave Subaerial Biofilms, Victoria E. Frazier

Masters Theses

Subaerial biofilms (SABs) grow at the interface between the atmosphere and rock surfaces in terrestrial and subterranean environments around the world. Multi-colored SABs colonizing relatively dry and nutrient-limited cave surfaces are known to contain microbes putatively involved in chemolithoautotrophic processes using inorganic carbon like carbon dioxide (CO₂) or methane (CH₄). However, the importance of CO₂ and CH₄ to SAB biomass production has not been quantified, the environmental conditions influencing biomass production and diversity have not been thoroughly evaluated, and stable carbon and nitrogen isotope compositions have yet to be determined from epigenic cave SABs. …

The Full Genome Sequence Of An Antarctic Microbe Constructed Using A Rapid, Portable Sequencer And A Hybrid Assembly, Bruce Wyatt Boles

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Microbial genomes contain combinations of nucleotides that code for genes which subsequently determines the function of the cell. This information provides significant insight into the unique niche of microbes from extreme environments. Here we use two sequencing technologies, the Oxford Nanopore MinION with accompanying software and Illumina HiSeq, to generate a hybrid genome for a Shewanella strain isolated from an Antarctic glacier. Bioinformatic programs, Albacore and SPAdes, allowed us to decrease the time of genome assembly while also obtaining a large quantity of information related to the Shewanella sp. Our combined approach yielded a high quality genome assembly 5.3 …

Ultramicrobacteria Genome Database Project, Abdullah A. Salim, Tien Tran, Andrew Putt, Terry C. Hazen

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Ultramicrobacteria (UMB) are a largely uncultured, globally abundant, and metabolically active group of bacteria. UMB have cell diameters ≤0.3μm, cell volumes ≤0.1 μm3, and small streamlined genomes. Recent findings indicate that UMB aid in bioremediation and nutrient cycling, but future investigations and comprehension of current findings are skewed by highly variable nomenclature and a lack of databases for functional, genomic, geochemical, or spatial data specific to candidate UMB. We aim to develop a user-friendly open-access database of various UMB candidates linked to an open-access online map where researchers can gather genomic, spatial, and geochemical data. Our comprehensive review of literature …

Iteratively Improving Hi-C Experiments One Step At A Time, Rosela Golloshi, Jacob T. Sanders, Rachel Patton Mccord

Faculty Publications and Other Works -- Biochemistry, Cellular and Molecular Biology

The 3D organization of eukaryotic chromosomes affects key processes such as gene expression, DNA replication, cell division, and response to DNA damage. The genome-wide chromosome conformation capture (Hi-C) approach can characterize the landscape of 3D genome organization by measuring interaction frequencies between all genomic regions. Hi-C protocol improvements and rapid advances in DNA sequencing power have made Hi-C useful to study diverse biological systems, not only to elucidate the role of 3D genome structure in proper cellular function, but also to characterize genomic rearrangements, assemble new genomes, and consider chromatin interactions as potential biomarkers for diseases. Yet, the Hi-C protocol …

Bioinformatic And Experimental Approaches For Deeper Metaproteomic Characterization Of Complex Environmental Samples, Ramsunder Mahadevan Iyer

Doctoral Dissertations

The coupling of high performance multi-dimensional liquid chromatography and tandem mass spectrometry for characterization of microbial proteins from complex environmental samples has paved the way for a new era in scientific discovery. The field of metaproteomics, which is the study of protein suite of all the organisms in a biological system, has taken a tremendous leap with the introduction of high-throughput proteomics. However, with corresponding increase in sample complexity, novel challenges have been raised with respect to efficient peptide separation via chromatography and bioinformatic analysis of the resulting high throughput data. In this dissertation, various aspects of metaproteomic characterization, including …

Assessment Of Genetic And Education Recovery Plan Objectives For The Bog Turtle (Glyptemys Muhlenbergii), Cassie Marie Dresser

Doctoral Dissertations

Unprecedented declines in biodiversity are threatening the natural world as we know it. Without human intervention, two thousand species listed under the US Endangered Species Act are likely to disappear. Fortunately, these species receive federal protection and increased research effort is needed to create and satisfy the objectives outlined in the mandated Species Recovery Plan. In this dissertation, I address three conservation objectives outlined in the Recovery Plan for North America’s smallest and rarest turtle, the Bog Turtle (Glyptemys muhlenbergii): (1) investigate the potential genetic differentiation in southern portions of the species’ range, (2) investigate the genetic impacts …

Detection, Diversity, And Evolution Of Fungal Nitric Oxide Reductases (P450nor), Steven Adam Higgins

Doctoral Dissertations

Nitrous oxide (N₂O) is a gas responsible for significant ozone layer depletion and contributes to greenhouse effects in Earth’s atmosphere. N₂O is primarily generated by denitrification, whereby nitrate (NO_3-) or nitrite (NO_2-) is converted to gaseous N₂O or N2. Teragram quantities of N₂O are emitted annually from agricultural soils treated with nitrogenous fertilizers due to the activity of soil microbiota. Although bacteria and fungi harbor genes permitting denitrification, fungi lack NosZ, an enzyme responsible for reducing N₂O into inert N2 gas. Historically, scientists have linked fungi …

Systematics, Diversification, And Functional Diversity Of Russulaceae (Russulales), Brian Patrick Looney

Doctoral Dissertations

The family Russulaceae is an iconic family of mushroom-forming Basidiomycetes both because of their importance as edible mushrooms in many parts of the world and their species richness in both temperate and tropical forested biomes. While much mycological research has been focused on this group, recent systematic and ecological research has failed to develop a comprehensive or cohesive organization by which to understand the evolutionary relationships, patterns of diversification, or functional importance of the group. Recently, interest in ectomycorrhizal fungi (EmF), of which Russulaceae is a key lineage, has greatly increased due to the recognition of the importance of EmF …

Role Of Hormonal And Developmental Signaling In Plant-Cyst Nematode Interaction, Sarbottam Piya

Doctoral Dissertations

Plant-parasitic cyst nematodes are one of the most destructive root parasites that cause severe yield losses in many crop plants. These obligate parasites induce a specialized multi-nucleate feeding site called syncytium. This study was conducted to explore the roles of phytohormones particularly auxin and ethylene, and miRNA-mediated crosstalk between development and defense responses in establishing the compatible interaction between Arabidopsis and Heterodera schachtii. Using yeast two-hybrid assay, a complete protein-protein interaction map between Auxin/indole-3-acetic acid (Aux/IAA) proteins and auxin response factors (ARFs) was generated. In addition, gene co-expression profiles of ARFs and Aux/IAAs were incorporated with protein-protein interaction data. …

Tetrameric Photosystem I: From Initial Discovery And Characterization In Chroococcidiopsis Sp. Ts-821 To Exploration Of Its Distribution And Understanding Of Its Significance In Cyanobacteria, Meng Li

Doctoral Dissertations

Photosystem I (PSI) forms trimeric complexes in most characterized cyanobacteria. We had reported the tetrameric form of PSI in the unicellular cyanobacterium, Chroococcidiopsis sp. TS-821 (TS-821). Using Cryo-EM, a 3D model of the PSI tetramer structure at 11.5 [Angstrom] resolution was obtained and a 2D map within the membrane plane of at 6.1 [Angstrom]. In contrast to the three-fold symmetry in trimeric PSI crystal structure from T. elongatus, two different inter-monomer interactions involving PsaLs are found in the PSI tetramer. Phylogenetic analysis based on PsaL protein sequences shows that TS-821 is closely related to heterocyst-forming cyanobacteria. Additionally, this tetrameric …

Computational Identification Of Terpene Synthase Genes And Their Evolutionary Analysis, Qidong Jia

Doctoral Dissertations

Terpenoids, the largest and most structurally and functionally diverse class of natural compounds on earth, are mostly synthesized by plants to be involved in various plant environment interactions. Some terpenoids are classified as primary metabolites essential for plant growth and development. Terpene synthases (TPSs), the key enzymes for terpenoid biosynthesis, are the major determinant of the tremendous diversity of terpenoid carbon skeletons. The TPS genes represent a mid-size family of about 30-100 functional genes in almost all major sequenced plant genomes. TPSs are also found in fungi and bacteria, but microbial TPS genes share low levels of sequence similarity and …

Application Of Hidden Markov Model Based Methods For Gaining Insights Into Protein Domain Evolution And Function, Amit Anil Upadhyay

Doctoral Dissertations

With the explosion in the amount of available sequence data, computational methods have become indispensable for studying proteins. Domains are the fundamental structural, functional and evolutionary units that make up proteins. Studying protein domains is an important part of understanding protein function and evolution. Hidden Markov Models (HMM) are one of the most successful methods that have been applied for protein sequence and structure analysis. In this study, HMM based methods were applied to study the evolution of sensory domains in microbial signal transduction systems as well as functional characterization and identification of cellulases in metagenomics datasets. Use of HMM …

Applications Of Evolutionary Bioinformatics In Basic And Biomedical Research, Ogun Adebali

Doctoral Dissertations

With the revolutionary progress in sequencing technologies, computational biology emerged as a game-changing field which is applied in understanding molecular events of life for not only complementary but also exploratory purposes. Bioinformatics resources and tools significantly help in data generation, organization and analysis. However, there is still a need for developing new approaches built based on a biologist’s point of view. In protein bioinformatics, there are several fundamental problems such as (i) determining protein function; (ii) identifying protein-protein interactions; (iii) predicting the effect of amino acid variants. Here, I present three chapters addressing these problems from an evolutionary perspective. Firstly, …

Distribution Of Abc Transporter Genes Across The Plant Kingdom, Thomas Scott Lane

Masters Theses

The ATP-binding cassette (ABC) transporter gene superfamily is ubiquitous among extant organisms. ABC transporters act to transport compounds across cellular membranes and are involved in a diverse range of biological processes and functions including cancer resistance in humans, drug resistance among vertebrates, and herbicide resistance in weeds. This superfamily of genes appears to be larger and more diverse in the plant kingdom—yet, we know relatively less about ABC transporter function in plants compared with mammals and bacteria. Therefore, we undertook a plant kingdom-wide transcriptomic survey of ABC transporters to better understand their diversity.

We utilized sequence similarity-based informatics techniques to …

Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood

Doctoral Dissertations

Microbial chemotaxis receptors (chemoreceptors) are complex proteins that sense the external environment and signal for flagella-mediated motility, serving as the GPS of the cell. In order to sense a myriad of physicochemical signals and adapt to diverse environmental niches, sensory regions of chemoreceptors are frenetically duplicated, mutated, or lost. Conversely, the chemoreceptor signaling region is a highly conserved protein domain. Extreme conservation of this domain is necessary because it determines very specific helical secondary, tertiary, and quaternary structures of the protein while simultaneously choreographing a network of interactions with the adaptor protein CheW and the histidine kinase CheA. This dichotomous …

Development Of An Experimental And Computational Platform For Enhanced Characterization Of Modified Peptides And Proteins In Environmental Proteomics, Ritin Sharma

Doctoral Dissertations

Over the last decade, mass spectrometry based proteomics has been established as the front-runner in systems-level protein expression studies. However, with the field progressing into research of more and more complex samples, novel challenges have been raised with respect to efficient protein extraction and computational matching. In this dissertation, various aspects in the proteomics workflow, including experimental and computational approaches, have been developed, optimized and systematically evaluated. In this work, some of the critical factors with respect to proteomics sample preparation, like available biomass, detergent removal methods, and intact protein fractionation to achieve deeper proteome measurements were evaluated. The presented …

R-Fap: Rapid Functional Annotation Of Prokaryotes Using Taxon-Specific Pan-Genomes And 10-Mer Peptides, Jordan Matthew Utley

Masters Theses

The growing implementation of next-generation sequencing technologies presents numerous fields with the opportunity to identify bacteria in near real-time. Fields such as counter-terrorism, forensics, medicine, and even microbial ecology are positioned to benefit from such advances and implementation. However, with the ability to rapidly produce high-quality sequence data comes the need to interpret this data as quickly as it is produced. While gene prediction algorithms have kept pace, functional prediction methods have not.

To bypass the need for large-scale queries to multiple databases for each newly-sequenced genome, the project detailed herein seeks to identify the genes shared within a taxonomic …

Single-Nucleotide Polymorphisms Associated With Performance Traits In Beef Cattle Grazing Endophyte-Infected Tall Fescue, Bryan Christopher Bastin

Masters Theses

Tall fescue (Lolium arundinaceum Schreb.) is the most prevalent forage in the Midsouth United States due in part to the presence of the endophytic fungus Neotyphodium coenophialum. The fungus, while conferring hardiness to tall fescue, contributes to decreased production efficiency in cow-calf operations. A previous genome-wide association study was performed using the Illumina 50k bovine SNP chip. Twenty-four SNP were found to be associated (P < 0.05) with adjusted birth weight and adjusted 205-day weights of calves from 48 beef cows at Ames Plantation. The first objective was to validate each SNP by testing associations with several additional phenotypes. Custom Taqman genotyping assays (Applied Biosystems, Foster City, CA) were subsequently designed to genotype each SNP in beef cattle located at Tennessee Tech University (n = 654), to validate associations in a large, independent herd. The results yielded 15 associations that were significant (P < 0.05) with 6 phenotypes linked to those affected by fescue toxicosis. The second objective investigated the link between fescue toxicosis and the XK, Kell blood group complex subunit-related, member 4 …

Development And Application Of Mass Spectrometry-Based Proteomics To Generate And Navigate The Proteomes Of The Genus Populus, Paul Edward Abraham

Doctoral Dissertations

Historically, there has been tremendous synergy between biology and analytical technology, such that one drives the development of the other. Over the past two decades, their interrelatedness has catalyzed entirely new experimental approaches and unlocked new types of biological questions, as exemplified by the advancements of the field of mass spectrometry (MS)-based proteomics. MS-based proteomics, which provides a more complete measurement of all the proteins in a cell, has revolutionized a variety of scientific fields, ranging from characterizing proteins expressed by a microorganism to tracking cancer-related biomarkers. Though MS technology has advanced significantly, the analysis of complicated proteomes, such as …

Genomic Analysis And Functional Characterization Of The Terpene Synthase Gene Family In Brachypodium Distachyon, Ayla Marie Norris

Masters Theses

Brachypodium distachyon is a small, temperate grass native to the Mediterranean region. While not agriculturally important, it possesses many characteristics such as rapid generation time, self-pollination, a small genome size, and ease of genetic transformation, that make it an attractive model organism for genetic studies. Brachypodium is closely related to other grasses of economical importance such as rice, sorghum, and especially wheat, and in fact it is the first member of the Pooideae grass sub-family to have its genome fully sequenced. Cereal grasses such as rice, sorghum, and maize have been reported to produce a class of secondary metabolites called …

Effects Of Folate Availability On Expression Of Adipocyte Metabolic Genes Via Modulation Of Dna Methylation, Julia Stair Gouffon

Doctoral Dissertations

Epigenetic modifications serve as a means of intermediate gene expression control and nutritional inputs may modify methylation patterns in regulatory regions of genes. Therefore, we proposed that specific nutrient availability of folate affects adipocyte development and metabolism through impacting the one-carbon cycle and subsequent DNA methylation patterns. Accordingly, we sought to determine if the methylation level of CpG islands could be influenced in adipocytes and if so, how this might affect gene signaling in mature adipocytes. We treated adipocytes with 0 to 0.9 millimolar [mM] folate, the methyl donor S-adenosylmethionine (SAMe) and the methylation inhibitor, 5-aza-2-deoxycitidine (2-DC) both during adipocyte …