Skip to Main Content

Basic Search

Skip to Search Results
 
 
 

Left Column

Filters

Show More

Show More

Show More

Right Column

Search Results

Search Results

(Total results 120)

Mini-Tools

 
 

Search Report

  • 1. Li, Jin Draft Genome Assembly, Organelle Genome Sequencing and Diversity Analysis of Marama Bean (Tylosema esculentum), the Green Gold of Africa

    Doctor of Philosophy, Case Western Reserve University, 2023, Biology

    Tylosema esculentum (marama bean) is an underutilized legume, long considered as a local potential crop due to its rich nutritional value. The reference plastome and mitogenome were assembled using a hybrid method with both Illumina and PacBio data. The diversity was explored with the WGS data of 84 samples from various geographic locations in Namibia and Pretoria. Phylogenetic analysis revealed two cytotypes with distinct plastomes and mitogenomes with differing levels of variability. Deep sequencing has identified heteroplasmy with both types of organellar genomes present, albeit one at a very low frequency. The inheritance of this complex of organellar genomes appears to be fairly constant, providing a conundrum of how the two genomes co-exist and are propagated through generations. The type 1 mitogenome has two autonomous rings with a total length of 399,572 bp, which can be restructured into five smaller circular molecules through recombination on 3 pairs of long direct repeats. The type 2 mitogenome contains a unique 2,108 bp sequence, which connects distant segments to form a new structure consisting of three circular molecules and one linear chromosome. This increased the copy number of nad9, rrns, rrn5, trnC, and trnfM. The two mitogenomes differed at another 230 loci, with only one nonsynonymous substitution in matR. cpDNA insertions were concentrated in one subgenomic ring of the mitogenome, including a 9,798 bp long fragment that contains potential psbC, rps14, psaA, and psaB pseudogenes. The two types of plastomes range in length from 161,537 bp to 161,580 bp, differing at 122 loci and at a 230 bp inversion. The chloroplast genes rpoC2, rpoB, and ndhD were found to be more diverse than other genes in marama plastome. 21.6 Gb PacBio HiFi data was assembled using Canu v2.2 into an unphased assembly of 1.24 Gb. k-mer analysis indicated that marama may be ancient tetraploid with an estimated genome size of only 277 Mb. The generated assembly has an N50 v (open full item for complete abstract)
    ... More

    Committee: Christopher Cullis (Advisor); Hillel Chiel (Committee Chair); Peter Zimmerman (Committee Member); Jean Burns (Committee Member); Sarah Bagby (Committee Member) Subjects: Bioinformatics; Genetics; Plant Biology

  • 2. Wheeler, Gregory Plant Carnivory and the Evolution of Novelty in Sarracenia alata

    Doctor of Philosophy, The Ohio State University, 2018, Evolution, Ecology and Organismal Biology

    Most broadly, this study aimed to develop a better understanding of how organisms evolve novel functions and traits, and examine how seemingly complex adaptive trait syndromes can convergently evolve. As an ideal example of this, the carnivorous plants were chosen. This polyphyletic grouping contains taxa derived from multiple independent evolutionary origins, in at least five plant orders, and has resulted in striking convergence of niche and morphology. First, a database study was performed, with the goal of understanding the evolutionary trends that impact carnivorous plants as a whole. Using carnivorous and non-carnivorous plant genomes available from GenBank. An a priori list of Gene Ontology-coded functions implicated in plant carnivory by earlier studies was constructed via literature review. Experimental and control samples were tested for statistical overrepresentation of these functions. It was found that, while some functions were significant in some taxa, there was no overall shared signal of plant carnivory, with each taxon presumably having selected for a different subset of these functions. Next, analyses were performed that targeted Sarracenia alata specifically. A reference genome for S. alata was assembled using PacBio, Illumina, and BioNano data and annotated using MAKER-P with additional preliminary database filtration. From these, it was found that Sarracenia alata possesses significant and substantial overrepresentation of genes with functions associated with plant carnivory, at odds with the hypothesis that the plant primarily relies on symbioses. Finally, pitcher fluid was collected from S. alata in the field. RNA was extracted from the fluid, sequenced via Illumina, and assembled with Trinity. Sequences were sorted into host plant and microbiome based on BLAST match to the S. alata reference genome. It was found that, while S. alata contributes two-thirds of the transcripts, these encode no digestive enzymes and a very limited set o (open full item for complete abstract)
    ... More

    Committee: Bryan Carstens Ph.D. (Advisor); Marymegan Daly Ph.D. (Committee Member); Zakee Sabree Ph.D. (Committee Member); Andrea Wolfe Ph.D. (Committee Member) Subjects: Bioinformatics; Biology; Botany

  • 3. ZHANG, YINGNAN Algorithms for Characterizing Chromatin Contacts Using Genome Architecture Mapping Data

    Doctor of Philosophy (PhD), Ohio University, 2025, Electrical Engineering & Computer Science (Engineering and Technology)

    The human genome is the blueprint of making a human. It contains all the genetic information needed to build an entire organism and is encoded in the DNA sequence. There are genes in DNA, which provide information for making proteins to perform the functions of the cells. Understanding the genome is essential for learning biological mechanisms, cell developments, and diseases. The 3D genome refers to the three-dimensional structure of the genome within the nucleus. With technologies such as Hi-C and Genome Architecture Mapping, scientists can study the relationship between chromatin interactions and gene regulation. However, there are limited bioinformatics tools that analyze the biological elements in chromatin contacts. In this dissertation, a bioinformatics pipeline that analyzes the feature pairs in chromatin contacts were developed and this pipeline was applied to three case studies. In the first case study pyramidal glutamatergic neurons and dopaminergic neurons were compared. The transcription factor binding sites on the open chromatin region of each cell type were determined, the feature pair analysis pipeline was applied to each cell type, and the transcription factor binding site pairs that have the highest discriminatory power between these two cell types were observed. The results show that the chromatin contacts with these strong discriminatory power transcription factor pairs contain more expressed genes, which are related to cell functions. The second case study compared two techniques that capture three-dimensional chromatin interactions: Genome Architecture Mapping (GAM) and Hi-C. The feature pair analysis pipeline used ChIP-seq data as features. It shows that GAM can capture more active chromatin interactions than Hi-C, while Hi-C captures more inactive chromatin interactions than GAM. The third case study explored early cell development, which analyzed the feature pairs between Embryonic Stem Cells (ESCs) and Extra-embryonic Endoderm (open full item for complete abstract)
    ... More

    Committee: Lonnie Welch (Advisor); David Juedes (Committee Member); Kevin Lee (Committee Member); Chang Liu (Committee Member); Chunmin Lo (Committee Member); Jundong Liu (Committee Member) Subjects: Computer Science

  • 4. Nordstedt, Nathan Isolation and characterization of novel bacterial strains to alleviate abiotic stress in greenhouse ornamental crops

    Doctor of Philosophy, The Ohio State University, 2021, Horticulture and Crop Science

    The production of greenhouse ornamental crops relies on extensive inputs of water and chemical fertilizers to produce high-quality plants for consumers. These inputs are both economically and resource expensive, leading to increased concerns of sustainability. In addition, ornamental crops can encounter water and nutrient stress throughout their life span, impacting their health, quality, and resiliency for consumers. Water stress decreases the health and quality of horticulture crops by inhibiting photosynthesis, transpiration, and nutrient uptake, contributing to a reduction in plant size and flower number. The lack of bioavailable nutrients for plant uptake negatively impacts plant metabolism, influencing different aspects of plant growth and development. The effect of both abiotic stresses decreases the salability of crops at retail and can impact consumer success in the landscape. Therefore, it is important that the horticulture industry has sustainable tools to decrease resource-intensive inputs while also increasing plant abiotic stress tolerance, without sacrificing crop quality. Plant growth promoting bacteria (PGPB) can increase plant growth under water and nutrient-limiting conditions by enhancing stress tolerance and increasing nutrient availability, uptake, and assimilation by plants. PGPB colonize their plant host and can stimulate plant growth and stress tolerance through a myriad of different mechanisms. The identification of PGPB for greenhouse ornamental crops will contribute to the formulation of commercial productions that can be implemented into greenhouse production systems for the sustainable production of high-quality and resilient crops. This work outlines the identification, evaluation, and characterization of PGPB for greenhouse ornamental crops subjected to water stress and low-nutrient conditions. A core collection of 45 bacterial isolates was utilized to develop a high-throughput approach for the selection and evaluation of PG (open full item for complete abstract)
    ... More

    Committee: Michelle Jones (Advisor); Christopher Taylor (Committee Member); Ye Xia (Committee Member); Jyan-Chyun Jang (Committee Member) Subjects: Horticulture; Plant Biology; Plant Pathology

  • 5. Paudel, Rajan An Investigation into the Evolution of Nucleotide Composition in the Human Genome

    Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2019, Biomedical Sciences (Bioinformatics and Proteomics/Genomics)

    Every human has about 100 novel mutations that are absent in the genomes of his/her parents. This intense influx of mutations degrades information that is stored in the DNA sequences and, at the same time, provides an opportunity for creation of new genetic messages. Currently, over one hundred million mutations have been characterized in the public databases. The dynamics of mutation have been investigated for decades in both experiments and sophisticated mathematical models, yet our understanding of genome evolution is still ambiguous. In this project, we computationally processed eighty million human mutations to get clear answers to basic questions about DNA evolution. Specifically, how is the non-randomness in nucleotide composition in vast genomic regions maintained? What biological forces preserve sequence non-randomness from being degraded by novel mutations? Our goal was to uncover peculiarities in dynamics of G+C nucleotide content and evaluate the equilibrium of GC-percentage in the human genome. We found that novel mutations that convert G:C pairs into A:T pairs are 1.39 times more frequent than opposite mutations that change A:T → G:C. This effect is more striking if we take into account the fact that the total number of G:C pairs (42%) is significantly less than the number of A:T pairs (58%). Hence, calculating per nucleotide pair, the mutations of G:C → A:T is 1.93 times more frequent than A:T → G:C mutations. Such bias should create fewer and fewer G:C pairs in the genomes from generation to generation, until it reaches equilibrium at 34% of GC-composition. However, the GC-percentage of the human genome is stable at 42%. There are two possible biological processes that may be responsible for preserving GC-composition from degradation: i) natural selection or ii) biased gene conversion. However, estimated parameters for both processes are unable to explain the maintenance of CG-percentage. We re-evaluated the biased gene conversion paramete (open full item for complete abstract)
    ... More

    Committee: Alexei Fedorov (Committee Chair); Robert Blumenthal (Committee Member); Sadik Khuder (Committee Member) Subjects: Bioinformatics; Biology

  • 6. Gluck Thaler, Emile Computational, Evolutionary and Functional Genetic Characterization of Fungal Gene Clusters Adapted to Degrade Plant Defense Chemicals

    Doctor of Philosophy, The Ohio State University, 2019, Plant Pathology

    Fungal interactions with plants pose both significant risks and benefits to global economies and ecosystems. As pathogens, fungi consume crops at our expense, and as mutualists and decayers, they maintain the health of fields, forests and soils. A key trait underlying these varied lifestyles is the ability to degrade toxic chemicals produced by plants to defend themselves from fungal attack. However, little is known about the genetic bases of these degradative (i.e., catabolic) mechanisms, or the evolutionary processes that give rise to adaptive catabolism, which has resulted in a fundamental gap in our understanding of how fungi adapt to their plant hosts. One promising approach to address these gaps in our knowledge is the study of metabolic gene clusters (MGCs), which are groups of neighboring genes that encode enzymatic, transporter and regulatory proteins participating in the same or related metabolic pathway. The self-contained nature of MGCs facilitates the discovery of genes encoding adaptive pathways, as well as investigations into the mechanisms shaping their evolution. Yet the extent to which catabolic genes form MGCs is unknown, largely due to a lack of tools suitable for their identification. The primary research objectives of this dissertation are thus twofold: to first develop computational tools for the identification of MGCs encoding the degradation of plant defense chemicals, and to then characterize the MGCs identified by these tools using phylogenetic and functional genetic analyses in order to elucidate the evolutionary processes driving fungal catabolic adaptation to plant tissues. In Chapter 1, I synthesize what is currently known about catabolic MGCs and their contributions to fungal ecological adaptation, with a focus on the evolutionary forces driving their assembly, maintenance and dispersal in fungal populations. In Chapter 2, I review the impact of one of these forces, horizontal gene transfer, on the evolution of eukaryotic microbial (open full item for complete abstract)
    ... More

    Committee: Jason Slot (Advisor); Ana Alonso (Committee Member); Pierluigi Bonello (Committee Member); Laura Kubatko (Committee Member) Subjects: Plant Pathology

  • 7. Adhikari, Binaya Understanding natural expression of cytoplasmic male sterility in flowering plants using a wildflower Lobelia siphilitica L. (Campanulaceae)

    PHD, Kent State University, 2018, College of Arts and Sciences / Department of Biological Sciences

    ADHIKARI, BINAYA, Ph. D., August 2018 BIOLOGY Understanding natural expression of cytoplasmic male sterility in flowering plants using a wildflower Lobelia siphilitica L. (Campanulaceae) Dissertation Advisor: Andrea L. Case, Ph. D. Cytoplasmic male sterility (CMS) is an interesting form of cytonuclear incompatibility found in flowering plants. Plants are male-sterile (or female) when mitochondrial CMS genes are expressed, but can produce viable pollen (hermaphrodites) if matching nuclear restorer genes suppress them. Because both CMS genes and their restorer genes are common in angiosperms, female plants are relatively rare. However, female plants have evolved hundreds of times, being found in about a third of plant families, creating questions about why the expression of male sterility is rare but taxonomically widespread. In theory, females should be found wherever multiple unique CMS genes are maintained within populations, either by natural selection or frequent invasion by new CMS genes. Empirical tests of these predictions are limited. Here, I evaluated CMS expression in Lobelia siphilitica (Campanulaceae). Populations of this species range from 0–100% female across eastern North America, making it useful for studying the evolution of female plants. I investigated whether and how variation in female frequency among populations relates to patterns of cytoplasmic gene sequence, mitochondrial gene expression and sex expression in controlled matings. I found that mitochondrial genomes of L. siphilitica evolve rapidly and show high diversity in populations with many females. Crossing experiments showed that high mitochondrial diversity reflected high CMS gene diversity within populations. Furthermore, some CMS types were widespread across populations, consistent with long-term maintenance by natural selection. Further research should study mitochondrial genomes to characterize CMS genes a (open full item for complete abstract)
    ... More

    Committee: Andrea Case (Advisor); Oscar Rocha (Committee Member); Christina Caruso (Committee Member); Srinivasan Vijayaraghavan (Committee Member); Soumitra Basu (Committee Member); John Portman (Committee Member) Subjects: Biology; Botany; Ecology; Evolution and Development; Genetics; Molecular Biology; Organismal Biology; Plant Biology; Plant Sciences

  • 8. Ghanem, Mostafa Development of Advanced Molecular Tools for Sequence Typing and Epidemiological Investigation of Avian Mycoplasma in Poultry

    Doctor of Philosophy, The Ohio State University, 2017, Comparative and Veterinary Medicine

    There are four avian mycoplasma species (spp.) that are pathogenic to poultry; Mycoplasma gallisepticum (MG), Mycoplasma synoviae (MS), Mycoplasma iowae (MI), and Mycoplasma meleagridis (MM). Avian mycoplasma caused infections represent significant economic burden on commercial poultry industry in the form of decreased egg and meat production efficiency, decreased market value of breeder flocks, carcass condemnation, and medication costs. Avian mycoplasma strain differentiation is a cornerstone for outbreak investigation, understanding infection dynamics, and epidemiology as well as planning future prevention and control strategies. Currently, avian mycoplasma strain differentiation is based on two main approaches; DNA fingerprinting and single or multiple locus based sequence typing. Despite that sequence typing approaches have many advantages over DNA fingerprinting approaches, they have many limitations. Recently due to the advanced next generation sequencing technologies, microbial whole genome sequencing (WGS) has become more feasible and resulted in a paradigm shift in the efficiency of outbreak investigation, understanding infection dynamics and epidemiology as well as planning future prevention and control strategies for many human and animal pathogens. The efficiency of WGS based strain differentiation approaches have superseded that of single or multiple loci based sequence typing approaches. The aim of this work was to improve and upgrade the currently used molecular typing tools for avian mycoplasma strain differentiation and in turn, epidemiological outbreak investigation via the development and application of state-of-the-art molecular typing approaches. This should be reflected in better prevention and control strategies and ultimately increasing the chances of successful eradication of avian mycoplasma spp. from commercial poultry. This dissertation is organized into an introduction and five chapters; the first chapter of this dissertation pres (open full item for complete abstract)
    ... More

    Committee: Mohamed El-Gazzar (Advisor) Subjects: Animal Diseases; Epidemiology; Microbiology; Veterinary Services

  • 9. Zhang, Yingxiao Genetic Engineering of Rubber Producing Dandelions

    Doctor of Philosophy, The Ohio State University, 2016, Horticulture and Crop Science

    Natural rubber (cis-1, 4-polyisoprene) is a biopolymer of significance used in both manufacturing and our daily lives. Unfortunately, the current rubber production system, based on the Para rubber tree (Hevea brasiliensis), is unsustainable due to increasing costs of manual latex collection, competition with other cash crops, and the pervasive threat of South American Leaf Blight, a fatal fungal pathogen. It is imperative to develop alternative rubber-producing crops. Rubber dandelion (Taraxacum kok-saghyz, TK) and Taraxacum brevicorniculatum (TB) are dandelion species which produce rubber in roots and have several desirable agronomic characteristics. TK is currently under development as an alternative rubber producing crop while TB is a model species for rubber biosynthesis. TK domestication will inevitably involve the introduction of novel traits through breeding or genetic modifications. To develop tools to monitor the potential gene flow between TK and its ubiquitous weedy relative, common dandelion (Taraxacum officinale, TO), chloroplast genomes have been sequenced for TK, TB and TO and chloroplast and nuclear species-specific markers have been developed and validated. The genomic and marker resources generated here provide a molecular tool kit for germplasm identification and gene flow studies. To advance crop improvement efforts by biotechnology, a rapid and hormone-free Agrobacterium rhizogenes-mediated transformation system was developed for TK and TB. By using root fragments as explants, non-composite transgenic plants were obtained within 8 weeks and the average transformation efficiency for TK and TB was 24.7% and 15.7%, respectively. Protocols developed here were used to transform TK and TB with rubber biosynthesis genes. The rate-limiting enzyme in the mevalonate pathway (MVA pathway), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), was introduced into TK and TB. Six genes encoding the entire MVA pathway were introduced into TK and the corresp (open full item for complete abstract)
    ... More

    Committee: Katrina Cornish Dr. (Advisor); Joshua Blakeslee Dr. (Advisor); John Cardina Dr. (Committee Member); Feng Qu Dr. (Committee Member) Subjects: Bioinformatics; Biology; Cellular Biology; Ecology; Horticulture; Molecular Biology; Plant Biology; Plant Sciences

  • 10. Yan, Ming Elucidating the Under-explored Genomic Diversity and Metabolic Potential of the Rumen Microbiome through Multi-Omics Approaches

    Doctor of Philosophy, The Ohio State University, 2024, Animal Sciences

    The rumen hosts a diverse array of prokaryotic (bacteria and archaea) and eukaryotic (fungi and protozoa) microbes. Collectively, they hydrolyze complex plant cell wall materials into simple sugars, which are further fermented into VFA, representing a substantial source of the host's energy needs. By incorporating inorganic ammonia generated from feed protein and urea, rumen microbes also provide a significant portion of the host's protein requirements. As regulators of the microbial ecosystem, rumen viruses (bacteriophages and eukaryotic viruses) also influence rumen fermentation and microbial protein synthesis. They achieve this by directly lysing microbes, thereby modulating microbial composition or by modifying the metabolism of infected bacterial cells. Additionally, they drive co-evolution between microbes and viruses, acting as vectors for horizontal gene transfer or through dynamic defense and counterdefense interactions with microbes. The anaerobic microbial cultivation techniques developed by Robert Hungate enable rumen microbiologists to explore the diverse spectrum of rumen microbial physiology and metabolism. However, despite continuous efforts in anaerobic cultivation, the culturable rumen microbes (including viruses) represent only a limited fraction of the overall diversity. Moreover, microbial cultures, whether monocultures or mixed cultures, fail to fully replicate the intricate microbial interactions observed in vivo, such as cross-feeding and predatory conditions. Fortunately, multi-omics technologies complement traditional culture-dependent analyses, enabling us to explore microbial ecology by uncovering the genomes (via genome-resolved metagenomics) and metabolism (via metatranscriptomics, metaproteomics and enzymatic activities) of the unculturable majority. Utilizing advancements in multi-omics and bioinformatics, this research aims to bridge the gap in rumen microbial genomics within the context of microbial ecology and rumen fermentation (open full item for complete abstract)
    ... More

    Committee: Zhongtang Yu Dr. (Advisor); Jeffrey Firkins Dr. (Committee Member); Tansol Park Dr. (Committee Member); Chanhee Lee Dr. (Committee Member); Alejandro Relling Dr. (Committee Member) Subjects: Animal Sciences; Bioinformatics; Microbiology

  • 11. Farleigh, Keaka Exploring the Genetic Basis of Local Adaptation

    Doctor of Philosophy, Miami University, 2024, Biology

    This dissertation is structured into five chapters. Chapter I: I provide a general introduction to my dissertation, primarily introducing the different influences on intraspecific variation and providing a background on local adaptation. Chapter II: I investigate the effects of environmental conditions and demographic history on populations of desert horned lizards (Phrynosoma platyrhinos). I evaluate the demographic history of P. platyrhinos and identify signatures of selection associated with climate, which may be indicative of local adaptation. I then link signatures of selection to genes and functional genomic elements. Chapter III: I explore the influence of environmental heterogeneity on intraspecific variation of the chisel-toothed kangaroo rat (Dipodomys microps). I discover signals of selection associated with both climate and vegetation. I also find evidence that selective pressures likely vary across the species distribution and develop a permutation test to identify populations that possess more putatively adaptive alleles than expected by chance. I also link signals of selection to genes and biological functions that may be related to previously identified morphological differences between populations. Chapter IV: I perform a meta-analysis to understand general patterns of putative local adaptation in terrestrial chordates. I use previously published datasets and analyze them using a common framework to test theoretical predictions regarding the relationship between environmental and demographic factors and signals of selection. I find that signals of selection follow theoretical predictions, and, importantly, find that constant variation is an important driver of signals of selection. Chapter V: I provide conclusions and future directions from my results.
    ... More

    Committee: Tereza Jezkova (Advisor); David Berg (Committee Member); Donghyung Lee (Committee Member); Richard Moore (Committee Member); Susan Hoffmann (Committee Member) Subjects: Bioinformatics; Biology; Climate Change; Evolution and Development

  • 12. Lewis, Zachary Urobiome: State of Knowledge, and Evaluation of Methods for Enabling Genome-Resolved Metagenomics of Urinary Tract Microbiota

    Master of Science, The Ohio State University, 2024, Veterinary Preventive Medicine

    The urinary tract contains a distinct and diverse set of microbiota (urobiome). Important work has established links between the composition of the urobiome and various diseases of the urinary tract, including bladder cancer, urolithiasis, incontinence, and recurrent urinary tract infection. However, efforts to characterize the urobiome and assess its functional potential have been limited due to technical challenges including low microbial biomass and high host cell shedding in urine. To begin addressing these challenges, we evaluate urine sample volume (100 l – 5 mL), and host DNA depletion methods and their effects on urobiome profiles in healthy dogs, which are a robust large animal model for the human urobiome. We collected urine from seven dogs and fractionated samples into multiple aliquots. One set of samples was additionally spiked with host (canine) cells to model a biologically relevant host cell burden in urine. Samples then underwent DNA extraction followed by 16S and shotgun metagenomic sequencing. We tested six methods of DNA extraction: QIAamp BiOstic Bacteremia (no host depletion), QIAamp DNA Microbiome, Molzym MolYsis, NEBNext Microbiome DNA Enrichment, Zymo HostZERO, and Propidium Monoazide. Sequences were processed and analyzed using QIIME2 and MetaPhlAn4. Metagenome assembled genomes (MAGs) were generated using MEGAHIT and MetaWRAP pipelines. Statistical analysis were performed in R. In relation to urine sample volume,  3.0 mL resulted in the most consistent urobiome profiling. In relation to host depletion, individual (dog) but not extraction method drove overall differences in microbial composition. DNA Microbiome yielded the greatest microbial diversity in 16S (p=0.0025) and shotgun metagenomic data (p=0.01), and maximized MAG recovery while effectively depleting host DNA (p=0.0039) in host-spiked urine samples. As proof-of-principle, we then mined MAGs for core metabolic functions and environmental chemical metabolism. We identified long c (open full item for complete abstract)
    ... More

    Committee: Virginia Rich (Committee Member); Vanessa Hale (Advisor); Brian Husbands (Committee Member) Subjects: Biomedical Research; Microbiology; Molecular Biology

  • 13. Javidi, Hamed DEEP NEURAL NETWORKS FOR COMPLEX DISEASE PREDICTION USING ELECTRONIC HEALTH RECORDS AND GENOMIC DATA

    Doctor of Philosophy in Engineering, Cleveland State University, 2024, Washkewicz College of Engineering

    Leveraging electronic health record data requires sophisticated methods that can optimally process this information to improve clinical decision-making. Artificial Intelligence (AI) promises to process healthcare data faster, for lower costs, and more accurately than conventional processes. Deep learning applied to longitudinal electronic health records (EHR) holds promise for disease prediction, but a systematic methods comparison has yet to be reported. Despite the promises of this technology, challenges remain in the current approaches to predicting a disease. There remains an unmet need for developing a gold-standard disease prediction framework for EHR data that can be reliably applied across many diseases. This research proposes a generalized deep learning approach that is amenable to predicting a vast number of diseases by integrating multiple streams of longitudinal clinical data and genomic features to maximize the predictive power over a broad spectrum of diseases. I provide empirical validation of the proposed solution using data from multiple datasets; including comprehensive simulated datasets and a real-world EHR datasets. The ultimate goal of this research is to develop a generalized deep learning approach that is amenable to predicting a vast number of diseases using longitudinal clinical data from the EHR.
    ... More

    Committee: Daniel Rotroff (Advisor); Donald Allensworth-Davies (Committee Member); Hongkai Yu (Committee Member); Sathish Kumar (Committee Member) Subjects: Computer Science

  • 14. Tian, Funing Ecological and metabolic roles of viruses in the ocean ecosystem

    Doctor of Philosophy, The Ohio State University, 2024, Microbiology

    Microbes are engines of ocean biogeochemical processes. Viruses influence and shape microbial communities via lysis, horizontal gene transfer, and metabolic reprogramming. Viral lysis facilitates the export of carbon from the surface into the deep ocean via aggregates of sinking particles. In fact, they outperform prokaryotes and eukaryotes as the strong predictor for carbon fluxes in the oligotrophic ocean. Viruses also impact the gene flow of their hosts, and the genes transferred from virus-host interactions can be fixed in viral genomes. Viruses are known to carry and express host-derived auxiliary metabolic genes (AMGs) that directly reprogram metabolisms within virus-infected cells, termed virocells. However, viral communities are poorly characterized in the oligotrophic ocean, and their AMG-driven metabolic reprogramming lacks systematic descriptions from the global oceans. The Sargasso Sea is highly stratified and nutrient-depleted each year in the summer months. This seasonal pattern makes the Sargasso Sea one of the ideal model ecosystems to study oligotrophic oceans. In the Sargasso Sea, abundance of viral-like particles has seasonal and depth-associated structuring patterns. Here, to better survey the Sargasso Sea viruses, we apply sequencing approaches to characterize viral communities via metagenomics and uncover their biogeographical and ecological structures locally and globally in the ocean. As described in Chapter 2, comparison with global viral metagenomics revealed that Sargasso Sea viruses were similar across warm oligotrophic oceanic regions but not represented globally. They form discrete populations in the viral and cellular fractions at the viral maximum (80m) and mesopelagic (200m) depths. Inclusion of long-read data captured 1,257 viral genomes in addition to the 1,044 viral genomes derived from short-read assemblies, resulting in the identification of ecologically important and microdiverse viral genomes. Having established lo (open full item for complete abstract)
    ... More

    Committee: Matthew Sullivan (Advisor); Joseph Tien (Committee Member); Virginia Rich (Committee Member); Igor Jouline (Committee Member) Subjects: Biogeochemistry; Bioinformatics; Biological Oceanography; Biology; Climate Change; Ecology; Environmental Science; Microbiology; Statistics; Virology

  • 15. Bliss-Schryer, Michael Identifying Ateles geoffroyi Individuals Noninvasively using Third-Generation Sequencing Technologies

    MA, Kent State University, 2024, College of Arts and Sciences / Department of Anthropology

    Genotyping animals is necessary for various field-based applications that require precise knowledge of the sampled individuals. Though feces are considered a low-quality source of host DNA, molecular techniques are increasingly prioritizing its usage for field-based noninvasive projects. Here, we describe a reproducible workflow to genotype individuals using a whole-genome sequencing approach with the portable, high throughput MinION MK1B and the BWA-GATK variant calling pipeline. After filtering, only 4 of the original 5,394 SNPs passed the filtering criteria, leading to an unsuccessful attempt to generate an informative multiloci SNP panel to confidently and accurately differentiate animals. In the filtered SNPs, 5 samples were entirely void of genotyping data. The majority of SNPs exhibited allelic dropout and a lack of called heterozygote genotypes, leading to the presumable false genotypes of the sampled individuals. On average, approximately 97% of the genome remained unsequenced, with only about one read covering each base in the mapped regions. Despite the limitations of employing a whole-genome sequencing approach to differentiate individuals with the MinION using feces, for species lacking known variants, this strategy may be an effective way to initially identify SNPs for subsequent resequencing and genotyping. Future studies are necessary to validate the authenticity of the identified SNPs and to assess their ability to discriminate individuals effectively with enrichment and targeted sequencing techniques.
    ... More

    Committee: Rafaela Takeshita (Advisor); Sangeet Lamichhaney (Committee Member); Richard Meindl (Committee Member); Anthony Tosi (Committee Member) Subjects: Bioinformatics; Genetics

  • 16. Klass, Taylor Integrated plant health management in the (meta)genomics era

    Doctor of Philosophy, The Ohio State University, 2024, Plant Pathology

    Often overshadowed by staple crops, vegetables contain many essential vitamins and minerals and play a key role in global food and nutritional security. However, vegetable production is threatened by a variety of diseases, including bacterial wilt and bacterial spot. My dissertation research utilizes genomic surveys to elucidate the diversity of the bacteria causing these diseases, both globally and locally. Bacterial wilt disease is endemic within the country of Cambodia, causing significant yield losses for Cambodian growers. However, the diversity of the Ralstonia solanacearum Species Complex (RSSC), the causal agent responsible for bacterial wilt disease, has not been defined in Cambodia. Therefore, we conducted a bacterial wilt survey within Cambodia, collecting RSSC isolates from four distinct host plants (tomato, hot pepper, long bean, and bitter gourd) over three locations, for a total of 24 RSSC isolates. We found that all 24 of the Cambodian RSSC isolates belong to phylotype I and are classified as Ralstonia pseudosolanacearum. Through disease progress assays on susceptible hosts, we observed that variation in the Cambodian isolate's ability to cause consistent wilt was dependent on the method of inoculation. Additionally, the Cambodian R. pseudosolanacearum isolates exhibited a wide range of phylogenomic diversity. When comparing the core and accessory genome and the Type III effector profile of the Cambodian isolates, we found that the R. pseudosolanacearum accessory genome better reflected the host of isolation and host range of the isolates compared to the core genome. Altogether, this research provides a glimpse into the RSSC diversity present within Cambodia and insight into R. pseudosolanacearum host range. Bacterial spot disease affects tomato and pepper production worldwide and is caused by a species complex of Xanthomonas bacteria: X. hortorum pv. gardneri, X. euvesicatoria pv. euvesicatoria, X. euvesicatoria pv. perforans, and X. vesicatoria. We (open full item for complete abstract)
    ... More

    Committee: Jonathan Jacobs (Advisor); Mary Rodriguez (Committee Member); Francesca Hand (Committee Member); Sally Miller (Advisor) Subjects: Plant Pathology

  • 17. Wissmann, Leela Impact of Geography on Access to Genetic Medicine Services for Children with Multiple Congenital Anomalies

    Master of Science, The Ohio State University, 2024, Genetic Counseling

    Background: Multiple congenital anomalies (MCA) are often present in rare diseases and ~80% of rare diseases are of genetic etiology. Many patients must undergo a lengthy diagnostic odyssey to identify a molecular diagnosis. The availability of genetics care varies geographically as genetics healthcare providers tend to be based in larger cities or academic institutions. This study aimed to understand geographical barriers to access to genetic healthcare for children with MCA. Methods: This is a retrospective study of Nationwide Children's Hospital (NCH) patients born between January 1, 2015 to September 15, 2023 who had ICD codes indicating MCA. Geographical location (urban or rural), childhood opportunity index, sex, race, ethnicity, NICU admittance, and epoch (whether genetic testing was initiated before or after 1/1/2020) from 6,144 patients were extracted from the NCH Enterprise Data Warehouse. Survival models were developed for two intervals: 1) time from International Classification of Disease (ICD) codes for MCA appearing in the medical record to the first encounter with a clinic capable of ordering genetic testing and 2) time from the first genetic test ordered to the final result received. Models were stratified by NICU admittance. Results: We found that rurality was not associated with time to event in either model. White patients with MCA were seen in testing-capable clinics sooner and more often than non-white patients, however, once seen, white and non-white patients had similar diagnostic odysseys. Patients who had genetic testing before 2020 were less likely to return for further testing with newly available modalities. Females not in the NICU were more likely to complete their diagnostic odyssey after the first genetic test was ordered compared to otherwise similar males. Discussion: These findings highlight disparities between white and non-white individuals for both NICU and non-NICU cohorts when looking at time from ICD codes for MCA appearin (open full item for complete abstract)
    ... More

    Committee: Bimal Chaudhari MD, MPH (Advisor); Rose Hokanson MS, LGC (Committee Member); Kate Shane-Carson MS, LGC (Committee Member) Subjects: Genetics; Health; Health Care; Medicine; Public Health

  • 18. Wilson, Jake Genomics Accelerated Discovery of Antimicrobial Natural Products from Bacteria

    Doctor of Philosophy, The Ohio State University, 2024, Pharmaceutical Sciences

    The emergence and spread of antimicrobial resistance (AMR) has created an urgent need for new antibiotics. Despite the looming threat of AMR, the antimicrobial drug development pipeline is sparse, and without action, return to a pre-antibiotic era is conceivable. Microbial natural products are the source of most clinically used antibiotics, and continue to be an excellent source of lead compounds. Further, the advent of genomics and detection of natural product biosynthetic gene clusters (BGCs) has revolutionized the study of microbial metabolism, making possible the targeted discovery of chemically unusual and biologically active compounds. Phosphonate natural products are defined by a direct C-P bond, and are renowned for their inhibitory properties. The phosphonate moiety is analogous to carboxylate and phosphate ester functional groups on primary metabolites, enabling chemical mimicry and competitive or suicide inhibition of essential metabolic enzymes. Biosynthesis of nearly all known phosphonates is initiated by phosphoenolpyruvate mutase (PepM), which catalyzes the isomerization of phosphoenolpyruvate to phosphonopyruvate, forming the characteristic C-P bond. Further, genes involved in phosphonate biosynthesis tend to co-localize with pepM on the genome of the producing organism in BGCs. Genome mining has proven to be an invaluable tool in phosphonate discovery efforts, enabling the targeted discovery of unprecedented enzymatic transformations and metabolites. This thesis describes genomics accelerated discovery of novel and bioactive phosphonate natural products from microbes. Phosphonoalamides are phosphonoalanine-containing peptides originally discovered in Streptomyces spp. While actinobacteria are the producers of most known phosphonates, bioinformatic analyses have shown that other taxa are replete with phosphonate biosynthetic potential. Detection of a phosphonoalamide BGC encoded by Bacillus spp. enabled the isolation of phosphonalamide E a (open full item for complete abstract)
    ... More

    Committee: Kou-San Ju (Advisor); Liva Rakotondraibe (Committee Member); Karl Werbovetz (Committee Member); James Fuchs (Committee Member) Subjects: Chemistry

  • 19. Kray, Kaitlyn Therapeutic Intervention to Rescue the SMA Phenotype and Elucidate the Functions Required to Rescue the Disease

    Doctor of Philosophy, The Ohio State University, 2024, Biochemistry Program, Ohio State

    Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by survival motor neuron (SMN) protein deficiency that results in motor neuron loss and muscle atrophy. SMN is encoded by two nearly identical genes in humans, SMN1 and SMN2 which functionally differ by a C to T change in exon 7. This change greatly reduces exon 7 inclusion from the majority transcripts from SMN2. The truncated SMN protein is unstable and rapidly degrades, resulting in reduced SMN levels. SMA patients have a mutation or loss of SMN1 and therefore, rely completely on the SMN2 gene for SMN production. It has been demonstrated in both animal models and humans that increasing SMN levels prior to onset of symptoms provides the greatest therapeutic benefit. Currently, there are three FDA approved SMN inducing therapies for treatment of SMA: antisense oligonucleotide, Spinraza™, gene replacement therapy Zolgensma™, and small molecule drug, Evrysdi™. While the current therapies are efficacious, many patients are symptomatic at diagnosis with varying levels of motor function and consequently, response to treatment is variable. Treatment after motor neuron loss has occurred is effective, although to a lesser degree. We treated three groups of severe SMA mice starting before, during, and after symptom onset to determine if combining the two mechanistically distinct SMN inducing therapies, the antisense oligonucleotide (ASO) and small molecule compound, could improve the therapeutic outcome both before and after motor neuron loss. We found, compared with individual therapies, dual treatment significantly increased FL-SMN transcript and protein production resulting in improved survival and weight of SMA mice. Additionally, when administered late symptomatically, motor unit function was completely rescued with no loss in function at 100 days of age in the dual treatment group. Therefore, we have shown this dual therapeutic approach successfully increases SMN protein and rescues motor (open full item for complete abstract)
    ... More

    Committee: Arthur Burghes PhD (Advisor); Kathrin Meyer PhD (Committee Member); Michael Kearse PhD (Committee Member); Michael Freitas PhD (Committee Member) Subjects: Biochemistry; Biomedical Research; Genetics; Molecular Biology; Neurobiology

  • 20. McGowan, Sean Utilizing an Organ-on-a-Chip to Study the Introduction of a Fecal Treatment at Hyperthermic Conditions

    Master of Science, The Ohio State University, 2024, Microbiology

    The human gut microbiome is the collection of the microbiota that reside in the human intestinal tract. Imbalances in the gut microbiome are associated with multiple diseases, so studying this is important for preventing and treating these conditions. These imbalances can have multiple causes, such as changes in core temperature. Previous work has indicated that the gut microbiome could play a role in mitigating negative effects of temperature on epithelial tissues, which could have profound effects on human health. Research into the human gut is normally performed by way of animal models, or by using a synthetic model involving the use of human cells on transwells. The goal of this study was to collect preliminary data to determine if gene expression in gut epithelial cells is influenced by the presence of a fecal sample at hypoxic, hyperthermic conditions. An experiment was performed on 36 gut-on-a-chips over the course of 48 hours at three different temperature levels: 30°C, 37°C, and 42°C. Next-Generation Sequencing (NGS) was performed to determine gene expression in the human epithelial cells when comparing the introduction of a fecal sample to the chip in low-oxygen conditions at 42°C. Most genes in the host cells were upregulated when exposed to the fecal sample, with the majority being involved in immune system responses, as well as cell growth and differentiation, host metabolism, and enzymatic activity, which is consistent with what would be expected when the gut bacteria are present. The gut-on-a-chip can be used to study temperature effects on the human epithelial cells, as well as test ways to counteract any negative effects that come with this shift. Future studies can elucidate the role that the gut microbiome may play in the response of the human body to changes in core temperature.
    ... More

    Committee: Karen Dannemiller (Committee Chair); Joshua Hagen (Committee Member); Justin North (Committee Member) Subjects: Biology