Bioinformatics Commons^™

The Genomics Of Champ1: Insights Into Their Cell-Type Specificity And Developmental Trajectories, Zoe Marie Van Caugherty

MUSC Theses and Dissertations

Chromosome alignment maintaining phosphoprotein 1(CHAMP1) is a gene that encodes a zinc finger protein that is involved in in the maintenance of kinetochore-microtubule attachment and regulating chromosome segregation in mitosis. (Itoh et al., 2011) CHAMP1 mutations have been shown to be major risk factors for neurodevelopmental disorders (NDDs) and autism spectrum disorder (ASD).(Asakura et al., 2021; Isidor et al., 2016; Levy et al., 2022) Although there is information on the link between CHAMP1 mutations and NDD, the role of CHAMP1 in regulating processes of human cortical development, namely, neurogenesis, proliferation, and electrophysiological properties of newly born neurons, is unknown. This …

Protein-Protein Interactions In Cell Cycle Proteins: An In Silico Investigation Of Two Important Players, Andriele Eichner

Dissertations, Theses, and Capstone Projects

The examination of the cell cycle carries significant implications for the biology, health, and overall existence of all living things. These implications span from the development and growth of these organisms to the aging process and cancer, as well as the potential of stem cell therapies to repair diseases and injuries. Numerous proteins of the cell cycle are essential for cellular division and proliferation and are widely conserved over the course of evolution. In this work, we aimed to investigate the molecular processes of protein-protein interactions in cell cycle proteins, centering on two key players: Cdc6 in budding yeast and …

Genomic Characterization Of Adolescent And Young Adult Cancers: Investigation Of Ewing Sarcoma Susceptibility And Chornobyl Thyroid Tumors, Olivia Lee

Dissertations & Theses (Open Access)

Adolescent and young adult (AYA) cancers, diagnosed between the ages of 15 and 39, can exhibit distinctive genetic and molecular characteristics. Reported epidemiologic findings and treatment outcomes based on pediatric and adult cancer studies are often not suitable for application to the AYA population, underscoring the need for more thorough genomic research. Advances in sequencing technologies have enabled comprehensive analyses of complex genomic characteristics of AYA cancers, crucial for understanding the underlying biology of these malignancies. Here, I have utilized advanced sequencing techniques and integrated analytic approaches to describe important genomic features in two different AYA cancer types: Ewing Sarcoma …

Predicting Marine Teleost Responses To Ocean Warming And Pollution, Akila Harishchandra

Electronic Theses and Dissertations

Ocean warming and pollution are two detrimental anthropogenic factors causing rapid marine ecosystem degradation recorded in the past decades. These factors alter the marine environment intolerable for many marine species, forcing them to either adapt or shift their contemporary habitat ranges to reduce the extinction risk embedded with environmental degradation. Estimating marine species’ habitat range shifts, and their potential for developing adaptive mechanisms are critical for ecosystem conservation and management, human health risk assessment, and climate change vulnerability assessments. Given that, for the first chapter of this thesis, we focused on developing a species distribution model (SDM) integrating marine species …

Evolution Of Overlapping Reading Frames In Virus Genomes, Laura Muñoz Baena

Electronic Thesis and Dissertation Repository

Viruses are formidable pathogens that represent the majority of biological entities in our planet, and their genomes are a source of interesting enigmas. One feature in which virus genomes are usually rich, is the presence of overlapping reading frames (OvRFs) — portions of the genome where the same nucleotide sequence encodes more than one protein. OvRFs are hypothesized to be used by viruses to encode proteins more compactly and to regulate transcription. In addition, OvRFs might be a source of gene novelty, facilitating the creation of new open reading frames (ORF) within the transcriptional context of existing ones.

To characterize …

Sequestered Sequences: A Bioinformatic Approach To The Forgotten Genome, Dylan Barth

UNLV Theses, Dissertations, Professional Papers, and Capstones

As high throughput sequencing generates ever increasing amounts of genetic and epigenetic data new lines of inquiry open up in the field of genomic research. In this thesis, we discuss three ways in which we can utilize public databases of next generation genomic data in order to study areas of the genome previously ignored by traditional approaches. These include the study of linker regions between domains of proteins, indirect enhancers that do not strongly contact promoters of genes they regulate, and transposon-derived enhancer elements. The work uncovers many exceptions to known biological principles, and adds nuance to our understanding of …

Exploration Of The Immune Landscape Of Ebv-Associated Gastric Cancers, Mikhail Salnikov

Electronic Thesis and Dissertation Repository

Epstein–Barr virus (EBV) is a gammaherpesvirus associated with 9% of all gastric cancers (GCs). EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology and patient prognosis. The purpose of this thesis is to investigate the tumor microenvironment (TME) of EBVaGCs, which has not been explored in-depth. We hypothesize that EBVaGCs and EBVnGCs are also distinct in terms of the molecular immune landscape. We employed over 400 stomach adenocarcinoma (STAD) samples from The Cancer Genome Atlas (TCGA), as well as a single cell dataset, for the construction of a web suite …

Utilizing Natural Language Processing For Automated Clinical Text Review: Identification Of Care Preference Documentation In Patients’ Discharge Summaries, Saksham Arora

Computer Science Senior Theses

Improving patient-centered care necessitates accurate documentation of care preferences, a crucial aspect often underrepresented in administrative data. Most studies apply care documentation to specific patient populations, rather than more appropriately broad population of `seriously ill' patients. This paper addresses this gap by leveraging transformer-based machine learning models, exhibiting an improvement over traditional keyword-based search methods in identifying care preference documentation.

In order to capture a broad spectrum of seriously ill patients, we matched decedent patients to non-decedent counterparts by utilizing a propensity score matching, accounting for important variables like age, gender, primary diagnoses and commodities. We trained and fine-tuned Bio_ClinicalBERT …

Understanding Host-Microbe Interactions In Maize Kernel And Sweetpotato Leaf Metagenomic Profiles., Alison K. Adams

Doctoral Dissertations

Functional and quantitative metagenomic profiling remains challenging and limits our understanding of host-microbe interactions. This body of work aims to mediate these challenges by using a novel quantitative reduced representation sequencing strategy (OmeSeq-qRRS), development of a fully automated software for quantitative metagenomic/microbiome profiling (Qmatey: quantitative metagenomic alignment and taxonomic identification using exact-matching) and implementing these tools for understanding plant-microbe-pathogen interactions in maize and sweetpotato. The next generation sequencing-based OmeSeq-qRRS leverages the strengths of shotgun whole genome sequencing and costs lower that the more affordable amplicon sequencing method. The novel FASTQ data compression/indexing and enhanced-multithreading of the MegaBLAST in Qmatey allows …

Computational Analysis Of Microbial Sequence Data Using Statistics And Machine Learning, Zhixiu Lu

Doctoral Dissertations

Since the discovery of the double helix of DNA in 1953, modern molecular biology has opened the door to a better understanding of how genes control chemical processes within cells, including protein synthesis. Although we are still far from claiming a complete understanding, recent advances in sequencing technologies, increased computational capacity, and more sophisticated computational methods have allowed the development of various new applications that provide further insight into DNA sequence data and how the information they encode impacts living organisms and their environment. Sequencing data can now be used to start identifying the relationships between microorganisms, where they live, …

Deephtlv: A Deep Learning Framework For Detecting Human T-Lymphotrophic Virus 1 Integration Sites, Johnathan Jia, Johnathan Jia

Dissertations & Theses (Open Access)

In the 1980s, researchers found the first human oncogenic retrovirus called human T-lymphotrophic virus type 1 (HTLV-1). Since then, HTLV-1 has been identified as the causative agent behind several diseases such as adult T-cell leukemia/lymphoma (ATL) and a HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). As part of its normal replication cycle, the genome is converted into DNA and integrated into the genome. With several hundreds to thousands of unique viral integration sites (VISs) distributed with indeterminate preference throughout the genome, detection of HTLV-1 VISs is a challenging task. Experimental studies typically use molecular biology …

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.

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

The Hepatic Immunological Pattern Shaped By Dominant-Subdominant Cellular Interactions Creates A Collective Function Beyond The Function Of Each Cellular Constituent To Orchestrate Progression Of Hepatocellular Carcinoma, Nicholas J. Koelsch

Theses and Dissertations

Abundance of data on the role of inflammatory immune responses in the progression or inhibition of hepatocellular carcinoma (HCC) has failed to offer a curative immunotherapy for HCC. This is largely because of taking reductionist approaches and missing the collective function of the hepatic immune system by focusing on specific immune cell types. To this end, we propose that focusing on the dominant-subdominant patterns of the immune cells would allow understanding of the mechanism by which a collective immune function emerges. To identify the collective immune function through a systems immunology perspective, we performed high-throughput analysis of snRNAseq data collected …

Bioinformatic Analysis Of Proteomic And Genomic Data From Nsclc Tumors On Prognostic And Predictive Factors Of Immunotherapy Treatment, Mark Wuenschel

Theses and Dissertations--Pharmacy

Recent lung cancer research has led to advancements in molecular immunology, resulting in development of small molecule inhibitors, or immune checkpoint inhibitors, that propagate an anti-tumor T cell response. Despite increased overall and progression-free survival with reduced adverse effects compared to traditional chemotherapy, treating advanced stage lung adenocarcinoma patients remains non-curative, and evidence of non-responders or tumor recurrence to immune checkpoint inhibitor therapy is growing. Also, compared to traditional chemotherapy, there is a lower percentage of patients who respond to small molecule inhibitors. In this analysis of proteomic and genomic data from The Cancer Proteome Atlas and Global Data Commons …

Identification Of Novel Biosynthetic Gene Clusters Encoding For Polyketide/Nrps-Producing Chemotherapeutic Compounds From Marine-Derived Streptomyces Hygroscopicus From A Marine Sanctuary, Hannah Ruth Flaherty

Honors Theses and Capstones

Nearly one out of six deaths in 2020, around ten million people, were caused by cancer, making it a leading cause of death worldwide (WHO, 2022). This major public health issue, in addition to the rise of multidrug-resistant (MDR) pathogens, provides a high demand for the discovery of new pharmaceutical drugs to be used clinically to treat these conditions. The Streptomyces genus accounts to produce 39% of all microbial metabolites currently approved for human health, indicating its potential as an important species to study for antimicrobial and anticancer agents. The long linear genome of Streptomyces contains specialized sequences known as …

Taxonomic Classification Of Viral And Bacterial Dna Following 2021 Avian Mass Mortality Event, Tessa Baillargeon

Honors Theses and Capstones

From May through July 2021, an unusual mortality event occurred along the eastern coast and Midwest of the United States. Thousands of birds, mostly from the order Passeriformes, were part of the die-off including blue jays (Cyanocitta cristata), common grackles (Quiscalus quiscula), European starlings (Sturnus vulgaris), American robins (Turdus migratorius). Clinical signs included crusted eyes, swollen conjunctiva, otitis, seizures, and ataxia.

The New Hampshire Veterinary Diagnostic Laboratory (NHVDL) received over 100 affected birds from various collaborators throughout the United States including Washington DC, NJ, CT, MD, and OH. Given the timing and geologic …

Cancer/Testis Gene Expression Changes In Metastatic Cancer, Clara M. Mosentine

Dissertations, Master's Theses and Master's Reports

Metastasis is the movement of cancerous cells to new parts of the body, often through the blood or lymph systems. Metastasis is classified as stage IV cancer, a prognosis that is significantly more difficult to effectively treat compared to earlier cancer stages. We are interested in assessing whether expression of Cancer/testis (CT) genes, a class of genes that are predominantly expressed in germ cells while also being abnormally expressed in a large percentage of cancers, is associated with cancer metastasis. Germ cells make up an organism’s reproductive system, such as the testis and ovaries, and exhibit cellular immortality and, in …

Vibes: A Workflow For Annotating And Visualizing Viral Sequences Integrated Into Bacterial Genomes, Conner J. Copeland

Graduate Student Theses, Dissertations, & Professional Papers

Bacteriophages are viruses that infect bacteria. Many bacteriophages integrate their genomes into the bacterial chromosome and become prophages. Prophages may substantially burden or benefit host bacteria fitness, acting in some cases as parasites and in others as mutualists, and have been demonstrated to increase host virulence. The increasing ease of bacterial genome se- quencing provides an opportunity to deeply explore prophage prevalence and insertion sites. Here we present VIBES, a workflow intended to automate prophage annotation in complete bacterial genome sequences. VIBES provides additional context to prophage annotations by annotating bac- terial genes and viral proteins in user-provided bacterial and …

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 …

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 …

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, …