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Phylogenetic Focusing Reveals The Evolution Of Eumetazoan Opsins, Curtis Provencher

Master's Theses and Capstones

Phylogenetic analyses of gene trees commonly begin by searching large molecular datasets from the taxa of interest using some known query sequence. Resulting sequences that exceed some threshold are then concatenated, aligned, and analyzed phylogenetically. This approach has revealed much about the evolutionary history of gene families, but several problems are apparent. Here we apply a new approach that we call Phylogenetic Focusing that circumvents some issues related to global search strategies. Our approach first circumscribes the largest possible orthogroup containing the gene family of interest and then proceeds to focus in on the gene family of interest based on …

Integrative Bioinformatics Approaches To Elucidating Prostate Cancer Cell Heterogeneity, Plasticity, And Treatment Response, Hsueh-Ping Chao

Dissertations & Theses (Open Access)

Prostate cancer (PCa) is the most common non-cutaneous tumor in American men, and the second leading cause of cancer-related deaths. PCa-related deaths can be attributed to heterogeneous tumors containing metastatic and therapy-resistant cancer cells. Cancer stem cells (CSC) are an important contributor to this tumor heterogeneity, which are present in primary tumors and become enriched in castration resistant PCa (CRPC). Our lab has demonstrated that the prostate cancer stem cells (PCSCs) are enriched in the phenotypically undifferentiated PCa cell population that lacks the expression of differentiation marker prostate-specific antigen (PSA). Our work has also demonstrated that PCa cells manifest significant …

High-Throughput Polygenic Biomarker Discovery Using Condition-Specific Gene Coexpression Networks, William Louis Poehlman

All Dissertations

Biomarkers can be described as molecular signatures that are associated with a trait or disease. RNA expression data facilitates discovery of biomarkers underlying complex phenotypes because it can capture dynamic biochemical processes that are regulated in tissue-specific and time-specific manners. Gene Coexpression Network (GCN) analysis is a method that utilizes RNA expression data to identify binary gene relationships across experimental conditions. Using a novel GCN construction algorithm, Knowledge Independent Network Construction (KINC), I provide evidence for novel polygenic biomarkers in both plant and animal use cases.

Kidney cancer is comprised of several distinct subtypes that demonstrate unique histological and molecular …

Microbial Ecology Of South Florida Surface Waters: Examining The Potential For Anthropogenic Influences, Chase P. Donnelly

HCNSO Student Theses and Dissertations

South Florida contains one of the largest subtropical wetlands in the world, and yet not much is known about the microbes that live in these surface waters. These microbes play an important role in chemical cycling and maintaining good water quality for both human and ecosystem health. The hydrology of Florida’s surface waters is tightly regulated with the use of canal and levee systems run by the US Army Corps of Engineers and The South Florida Water Management District. These canals run through the Everglades, agriculture, and urban environments to control water levels in Lake Okeechobee, the Water Conservation Areas, …

Cultivating Ecosystems: Microbial Communities In Recirculating Aquaculture Systems, Ryan Bartelme

Theses and Dissertations

Intensive cultivation of fish is necessary to meet future global market demands. Recirculating aquaculture systems (RAS) enable dense growth of fish, while occupying less space than traditional aquaculture farms. However, RAS often experience complications and high fish mortalities due to disease and improper waste management. In properly functioning systems, the microorganisms associated with fish (gut, scales) as well as those found in the system environment (water, component surfaces) remove waste and maintain fish health by discouraging growth of opportunistic pathogens. Previous RAS microbiome studies are small in scope, utilize coarse methods, and contain limited long-term spatial or temporal data. With …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

Efficient Algorithms For Trees And Networks In Evolutionary Genomics, Sajad Mirzaei

Doctoral Dissertations

Phylogenetic networks are graphs used to abstractly or explicitly visualize the evolutionary relationships between genes, genomes, species, nucleotide sequences, chromosomes, etc. Reticulation events such as hybridization, horizontal gene transfer, recombination, population admixture, gene duplication, etc. are shown in such networks. Phylogenetic trees are a subset of phylogenetic networks used in the absence of such events.

In this dissertation, we focus on some of the existing problems in phylogenetics.

First, we propose a heuristic method called PIRN_S to build near optimal so-called ``hybridization networks" from a given set of phylogenetic trees (called gene trees), representing evolutionary history, such that trees are …

A Study Of Scalability And Cost-Effectiveness Of Large-Scale Scientific Applications Over Heterogeneous Computing Environment, Arghya K. Das

LSU Doctoral Dissertations

Recent advances in large-scale experimental facilities ushered in an era of data-driven science. These large-scale data increase the opportunity to answer many fundamental questions in basic science. However, these data pose new challenges to the scientific community in terms of their optimal processing and transfer. Consequently, scientists are in dire need of robust high performance computing (HPC) solutions that can scale with terabytes of data.

In this thesis, I address the challenges in three major aspects of scientific big data processing as follows: 1) Developing scalable software and algorithms for data- and compute-intensive scientific applications. 2) Proposing new cluster architectures …

A Systems Chemical Biology Approach For Dissecting Differential Molecular Mechanisms Of Action Of Clinical Kinase Inhibitors In Lung Cancer, Natalia Junqueira Sumi

USF Tampa Graduate Theses and Dissertations

Lung cancer is the second most common cancer type and is associated with high mortality rates. The survival rate for lung cancer patients has increased slowly in the last decade mainly as the result of the development of novel targeted and immune therapies. However, non-small cell lung cancer patients lacking known or actionable driver mutations and small cell lung cancer patients with recurrent disease are still in urgent need of new therapies. Drug repurposing is an efficient way to identify new therapies since it uses clinically relevant small molecule drugs. Determination of off-targets of small molecules is a novel approach …

Mining The Red Sea Metagenomics Libraries For Betaine Pathways, Sherouk Allam

Theses and Dissertations

Glycine Betaine (GB) is a fundamental solute for salinity tolerance in many organisms. Our aim in this study was to identify the GB pathway in highly complex natural community inhabiting brine pool and Red Sea column in Atlantis II Red Sea. Environmental genomics is a powerful tool for collecting information on microbial communities. Knowledge can be collected about highly complex natural communities. Microbial community living in extreme conditions evolved divers molecular mechanisms to withstand these conditions. Metagenomic libraries from Atlantic II samples were used to study betaine biosynthetic pathway that is more abundant. Betaine is synthesized independently from two different …

Genomewide Evaluation Of Cis-Elements And Cognate Transcription Factors In Nicotiana Attenuata Predicts 27 Unique Transcription Factor-Binding Site Pairs, Ashton Omdahl

Undergraduate Honors Theses

Nicotiana attenuata has been widely studied for its ecological plant-herbivore relationships and response to environmental stress. The jasmonate signaling pathway regulated by jasmonate ZIM-domiain (JAZ) repressor proteins that modulate defense response levels has been of particular focus in this research. While our understanding of the genes associated with defense response and their regulation continues to expand, the transcriptional regulation of these genes is largely uncharacterized. In an effort to provide insight into these relationships, we performed genomewide analysis of transcript level data in order to predict transcription factors (TFs), their respective binding sites (TFBS), and the genes they regulate. We …

Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar

Arts & Sciences Electronic Theses and Dissertations

Paired tumor-normal sequencing of thousands of patient’s exomes has revealed millions of somatic mutations, but functional characterization and clinical decision making are stymied because biologically neutral ‘passenger’ mutations greatly outnumber pathogenic ‘driver’ mutations. Since most mutations will return negative results if tested, conventional resource-intensive experiments are reserved for mutations which are observed in multiple patients or rarer mutations found in well-established cancer genes. Most mutations are therefore never tested, diminishing the potential to discover new mechanisms of cancer development and treatment opportunities. Computational methods that reliably prioritize mutations for testing would greatly increase the translation of sequencing results to clinical …

Comparison Of Otus And Asvs In 73 Bird Species From Equatorial Guinea, Darien Capunitan

Master's Theses

As scientists discover more information about the communities of bacteria that live on and inside hosts, "the microbiome", a new avenue for understanding the health of humans and animals has opened. There are many analysis pipelines for microbiome data processing, and choice of analytical tools can affect the biological results of the analysis. The current analysis climate does not point toward a single most effective protocol, which hinders comparisons across studies. An important step in microbiome data processing is the assignment of reads into groups of similar organisms. The traditional unit for grouping organisms is the species; however resolving sequences …

Evolution Of Bordetella Pertussis Genome May Play A Role In The Increased Rate Of Whooping Cough Cases In The United States, Kevin Loftus

Senior Honors Projects, 2010-2019

Bordetella pertussis is the bacterium responsible for pertussis, a disease commonly referred to as whooping cough. Recently, pertussis has made a resurgence in the U.S. despite high-vaccination coverage. Possible causes of the increased number of pertussis cases include genetic evolution of B. pertussis, increased awareness of the disease, better laboratory diagnostics, and the switch from a whole-cellular (wP) vaccine to an acellular vaccine (aP) in the 1990s. Fortunately, just as B. pertussis is evolving, so is the arsenal of technologies used to understand and combat this pathogenic bacterium. Whole genome sequencing is one technology that helps researchers better understand …

Functional Signature Ontology-Based Identification And Validation Of Novel Therapeutic Targets And Natural Products For The Treatment Of Cancer, Beth Neilsen

Theses & Dissertations

Multiple studies have revealed that Ras-driven tumors acquire vulnerabilities by adapting cellular mechanisms that promote uncontrolled proliferation and suppress apoptosis. Kinase Suppressor of Ras 1 (KSR1) modulates ERK activation downstream of oncogenic Ras, and knockdown of KSR1 selectively kills malignant, Ras-driven cancer cells, but does not kill immortalized, non-transformed human colon epithelial cells (HCECs). KSR1^-/- mice are fertile and phenotypically normal, but resistant to Ras-driven tumor formation suggesting KSR1 represents a vulnerability in cancer cells.

To identify additional vulnerabilities in cancer, a screening approach termed Functional Signature Ontology (FUSION) was used to screen 14,355 genes and 1,200 natural product …

Novel Algorithms For Some Fundamental Big Data Problems, Abdullah-Al Mamun

Doctoral Dissertations

In this digital era data sets are growing rapidly. Storing, processing, and analyzing large volume of data require efficient techniques. These techniques deal with big data problems by providing time efficient methods, effective external memory algorithms, parallel and high performance solutions, and so on. This thesis studies three important areas of big data problems and presents state of the art approaches to address them.

The first part of this thesis discusses the k-mer counting problem. A massive number of bioinformatics applications require counting of k-length substrings in genetically important long strings. Genome assembly, repeat detection, multiple sequence alignment, …

Genomic Data Mining For Functional Annotation Of Human Long Noncoding Rnas, Brian L. Gudenas

All Dissertations

Life may have begun in an RNA world, which is supported by the increasingly vital role that RNA has been shown to perform in biological systems. To understand how the genome encodes life, one must look to the transcriptome, the set of all RNA molecules in a cell. The transcriptome illustrates which RNA transcripts are expressed at what times and this orchestrated network of gene expression is responsible for multicellular development. In humans, most genes are noncoding RNAs, meaning that they do not encode proteins. The largest class of noncoding genes are long noncoding RNAs (lncRNAs), RNA transcripts greater in …

End-To-End Learning Framework For Circular Rna Classification From Other Long Non-Coding Rnas Using Multi-Modal Deep Learning., Mohamed Chaabane

Electronic Theses and Dissertations

Over the past two decades, a circular form of RNA (circular RNA) produced from splicing mechanism has become the focus of scientific studies due to its major role as a microRNA (miR) ac tivity modulator and its association with various diseases including cancer. Therefore, the detection of circular RNAs is a vital operation for continued comprehension of their biogenesis and purpose. Prediction of circular RNA can be achieved by first distinguishing non-coding RNAs from protein coding gene transcripts, separating short and long non-coding RNAs (lncRNAs), and finally pre dicting circular RNAs from other lncRNAs. However, available tools to distinguish circular …

Manual And Automatic Translation From Sequential To Parallel Programming On Cloud Systems, Bing Li

Computer Science Dissertations

Cloud computing has gradually evolved into an infrastructural tool for a variety of scientific research and computing applications. It has become a trend for many institutions and organizations to migrate their products from local servers to the cloud. One of the current challenges in cloud computing is running software efficiently on cloud platforms since many legacy codes cannot be executed in parallel in cloud contexts, which is a waste of the cloud’s computing power. To solve this problem, we have researched ways to translate code from sequential to parallel cloud computing using three categories of translation methods: manual, automatic, and …

The Identification Of Genes And Brain Patterns In The Quantitative Trait Loci Of Chromosome 5, Kimberly Diaz Perez

Psychology Honors Theses

In previous research, Gupta et al. (2015) analyzed gray matter density as well as volume reductions related to schizophrenia in the region of the insula and medial prefrontal cortex. Sprooten et al. (2015) then identified a set of quantitative trait loci (QTLs), which is a region of DNA associated with variability in these gray matter concentration patterns. The aim of this study is to examine the QTL they found in a region of chromosome 5. We hypothesized that there will be a set of genes in the QTL on chromosome 5 that is related to abnormal brain patterns in potential …

Analysis Of Grape Berry Epiphytic Microbiomes Via Qiime, Isabelle O'Bryon

Theses

Research in the wine industry has previously characterized many aspects of the wine making process from soil fertility to the community of microbes in must and wine, but the epiphytic bacterial and fungal communities have not been studied throughout grape development. This project aims to investigate the epiphytic grape microbiome to better understand its role in disease and grape development, and the effects of terroir on the microbiome, by examining the epiphytic microbiome of developing and sour rot infected grapes in New York and Tasmania. Sour rot is characterized by a distinct vinegar smell that is caused by the combination …

Efficient Alignment Algorithms For Dna Sequencing Data, Nilesh Vinod Khiste

Electronic Thesis and Dissertation Repository

The DNA Next Generation Sequencing (NGS) technologies produce data at a low cost, enabling their application to many ambitious fields such as cancer research, disease control, personalized medicine etc. However, even after a decade of research, the modern aligners and assemblers are far from providing efficient and error free genome alignments and assemblies respectively. This is due to the inherent nature of the genome alignment and assembly problem, which involves many complexities. Many algorithms to address this problem have been proposed over the years, but there still is a huge scope for improvement in this research space.

Many new genome …

A Cure For Salmonella: Engaging Students In Pathogen Microbiology And Bioinformatics, Sophie Jurgensen

Senior Honors Projects, 2010-2019

Advances in Next Generation Sequencing (NGS) technology have generated a vast amount of publicly available genomic data, creating a need for students with training in computational analysis. This laboratory lesson is a course-based undergraduate research experience (CURE) focusing on environmental Salmonella, a common foodborne pathogen that is of great interest to public health laboratories but is relatively less virulent than most other such pathogens. As discovery is a central tenet of CUREs, students isolate novel Salmonella enterica and related strains from stream sediment, poultry litter, or other sources in the first half of the lesson (Module 1). They also …

Scalable Feature Selection And Extraction With Applications In Kinase Polypharmacology, Derek Jones

Theses and Dissertations--Computer Science

In order to reduce the time associated with and the costs of drug discovery, machine learning is being used to automate much of the work in this process. However the size and complex nature of molecular data makes the application of machine learning especially challenging. Much work must go into the process of engineering features that are then used to train machine learning models, costing considerable amounts of time and requiring the knowledge of domain experts to be most effective. The purpose of this work is to demonstrate data driven approaches to perform the feature selection and extraction steps in …

An Interdisciplinary Approach To The Target Elucidation Of Novel Antibiotic 31g12, Larissa A. Walker

Graduate Student Theses, Dissertations, & Professional Papers

Staphylococcus aureus is a Gram-positive bacterial pathogen responsible for nosocomial and community-acquired infections that can quickly acquire antibiotic resistance. We have identified a novel triazole antimicrobial 31G12 based on the natural product core of nonactin isolated from the fermentation of Streptomyces griseus, that is active against many Gram-positive bacteria as well as antibiotic resistant methicillin-resistant S. aureus and vancomycin-resistant Enterococcus. The synthesis and characterization indicate that 31G12 exists as a mixture of two rotamers at room temperature and displays bacteriostatic activity against S. aureus with moderate mammalian cell toxicity. We have currently identified potential protein targets of 31G12 in …

Discovering Driver Mutations In Biological Data, Yahya Bokhari

Theses and Dissertations

Background

Somatic mutations accumulate in human cells throughout life. Some may have no adverse consequences, but some of them may lead to cancer. A cancer genome is typically unstable, and thus more mutations can accumulate in the DNA of cancer cells. An ongoing problem is to figure out which mutations are drivers - play a role in oncogenesis, and which are passengers - do not play a role. One way of addressing this question is through inspection of somatic mutations in DNA of cancer samples from a cohort of patients and detection of patterns that differentiate driver from passenger mutations. …

Genetic Influences On Rheumatoid Arthritis In Global Populations, Vincent Albert Laufer

All ETDs from UAB

Rheumatoid arthritis (RA) is a complex disease having numerous genetic and environmental risk factors the interplay of which produces RA pathobiology. While the sheer number of genetic and environmental risk factors complicates understanding of disease biology, understanding has progressed far enough for insight into the most likely mechanisms for the development of the disease. Modern studies of the genetics of RA are massively parallel, enabling researchers to systematically interrogate variants throughout the human genome for associations in genome-wide association studies or GWAS. Such studies have been carried out in European and Asian cohorts many times, and the most recent RA …