Life Sciences Commons^™

Development Of An In Silico Kir Genotyping Algorithm And Its Application To Population And Cancer Immunogenetic Analyses, Howard Rosoff

Dissertations & Theses (Open Access)

Gene content determination and variant calling in the complex KIR genomic region are useful for immune system function analysis, pathogenesis and disease risk factor elucidation, immunotherapy development, evolutionary investigations, and human migration modeling. Sequence-specific oligonucleotide and sequence-specific primer PCR methods are the de facto standards for KIR presence/absence identification, but the current platforms are unsuitable for SNP calling, impractical for KIR typing large cohorts of DNA samples, and inapplicable for typing repositories in which sequence data, but not cells or cell analytes, are available. Alternative typing methods, such as in silico sequence-based typing, can address the problems associated with amplicon-based …

Incremental Phylogenetics By Repeated Insertions: An Evolutionary Tree Algorithm, Peter Revesz, Zhiqiang Li

School of Computing: Faculty Publications

We introduce the idea of constructing hypothetical evolutionary trees using an incremental algorithm that inserts species one-by-one into the current evolutionary tree. The method of incremental phylogenetics by repeated insertions lead to an algorithm that can be used on DNA, RNA and amino acid sequences. According to experimental results on both synthetic and biological data, the new algorithm generates more accurate evolutionary trees than the UPGMA and the Neighbor Joining algorithms.

Protein Residue-Residue Contact Prediction Using Stacked Denoising Autoencoders, Joseph Bailey Luttrell Iv

Honors Theses

Protein residue-residue contact prediction is one of many areas of bioinformatics research that aims to assist researchers in the discovery of structural features of proteins. Predicting the existence of such structural features can provide a starting point for studying the tertiary structures of proteins. This has the potential to be useful in applications such as drug design where tertiary structure predictions may play an important role in approximating the interactions between drugs and their targets without expending the monetary resources necessary for preliminary experimentation. Here, four different methods involving deep learning, support vector machines (SVMs), and direct coupling analysis were …

Automated Quality Control For Genome Wide Association Studies, Sally R. Ellingson, David W. Fardo

Institute for Biomedical Informatics Faculty Publications

This paper provides details on the necessary steps to assess and control data in genome wide association studies (GWAS) using genotype information on a large number of genetic markers for large number of individuals. Due to varied study designs and genotyping platforms between multiple sites/projects as well as potential genotyping errors, it is important to ensure high quality data. Scripts and directions are provided to facilitate others in this process.

Use Of Clustering Techniques For Protein Domain Analysis, Eric Rodene

Department of Computer Science and Engineering: Dissertations, Theses, and Student Research

Next-generation sequencing has allowed many new protein sequences to be identified. However, this expansion of sequence data limits the ability to determine the structure and function of most of these newly-identified proteins. Inferring the function and relationships between proteins is possible with traditional alignment-based phylogeny. However, this requires at least one shared subsequence. Without such a subsequence, no meaningful alignments between the protein sequences are possible. The entire protein set (or proteome) of an organism contains many unrelated proteins. At this level, the necessary similarity does not occur. Therefore, an alternative method of understanding relationships within diverse sets of proteins …

Mutation Selection On The Metabolic Pathway And The Effects On Protein Co-Evolution And The Rate Limiting Steps On The Tree Of Life, Katherine S. Porter

Mathematics Summer Fellows

Metabolic pathways are made of a series of reactions by enzymes at different speeds. These pathways include the rate limiting step, which is the slowest step that determines the rate of the overall reaction. To date, one study has examined the pathway of glycolysis and found no evidence of evolutionary stability of its rate limiting step. In addition, phylogenetic evidence has shown evolution in the pathway over time including gene duplication and positive selection within the pathway. This evidence suggests that there is coevolutionary selection on glycolysis. The evidence from this previous study is simulation-based. The Michaelis-Menten kinetics that describe …

Ciliate Codon Translator Program Manual, Quentin D. Altemose

Mathematics Summer Fellows

Understanding the evolutionary history of organisms allows us to better comprehend selective pressures and their effects on larger populations. In our study, we focused on analyzing the DNA of ciliate groups, which are single celled protozoans characterized by the presence of cilia on their outer membrane. We utilized the DNA of the organisms to analyze the changes in population genotype over time. We tested existing evolutionary models (designed to represent natural genetic variation over time in populations) against our data to identify the model with the best fit and likelihood. From the DNA and the evolutionary model with the highest …

Ten Simple Rules For Taking Advantage Of Git And Github, Yasset Perez-Riverol, Laurent Gatto, Rui Wang, Timo Sachsenberg, Julian Uszkoreit, Felipe Da Veiga Leprevost, Christian Fufezan, Tobias Ternent, Stephen J. Eglen, Daniel S. Katz, Tom J. Pollard, Alexander Konovalov, Robert M. Flight, Kai Blin, Juan Antonio Vizcaíno

Molecular and Cellular Biochemistry Faculty Publications

No abstract provided.

Novel Advancements For Improving Sprout Safety, Kyle S. Landry

Doctoral Dissertations

All varieties of bean sprouts (mung bean, alfalfa, broccoli, and radish) are classified as a “super-food” and are common staples for health conscious consumers. Along with the proposed health benefits, there is also an inherent risk of foodborne illness. When sprouts are cooked, there is little risk of illness. The purpose of this dissertation was to explore novel techniques to minimize or prevent the incidence of foodborne illness associated with the consumption of sprouts. Three areas were investigated: 1) the use of a biocontrol organism, 2) the use of a novel spontaneous carvacrol nanoemulsion, and 3) the influence of the …

Bringing Toxicology Into The 21st Century: A Global Call To Action, Troy Seidle, Martin Stephens

Martin Stephens, PhD

Conventional toxicological testing methods are often decades old, costly and low-throughput, with questionable relevance to the human condition. Several of these factors have contributed to a backlog of chemicals that have been inadequately assessed for toxicity. Some authorities have responded to this challenge by implementing large-scale testing programmes. Others have concluded that a paradigm shift in toxicology is warranted. One such call came in 2007 from the United States National Research Council (NRC), which articulated a vision of ‘‘21st century toxicology” based predominantly on non-animal techniques. Potential advantages of such an approach include the capacity to examine a far greater …

A Mechanical Study Of Cancer Drug-Receptor Interactions, Specifically In G-Quadruplex Dna And Topoisomerase I Enzymes, Kelly Ann Mulholland

Theses and Dissertations

Computational methods are becoming essential in drug discovery as they provide information that traditional drug development methods lack. Using these methods to understand drug-receptor interactions in detail, researchers are able to efficiently design promising drug candidates. In this study, extra precision Glide docking, molecular dynamics simulations and MMGBSA binding energy calculations provided information about the binding behavior of small molecules to two specific targets for current cancer therapeutics: G-quadruplex DNA and Topoisomerase I enzyme. The first study focuses on the compound Telomestatin, which induces apoptosis of various cancer cells with a relatively low effect on somatic cells due to its …

A Dynamic Run-Profile Energy-Aware Approach For Scheduling Computationally Intensive Bioinformatics Applications, Sachin Pawaskar, Hesham Ali

Computer Science Faculty Proceedings & Presentations

High Performance Computing (HPC) resources are housed in large datacenters, which consume exorbitant amounts of energy and are quickly demanding attention from businesses as they result in high operating costs. On the other hand HPC environments have been very useful to researchers in many emerging areas in life sciences such as Bioinformatics and Medical Informatics. In an earlier work, we introduced a dynamic model for energy aware scheduling (EAS) in a HPC environment; the model is domain agnostic and incorporates both the deadline parameter as well as energy parameters for computationally intensive applications. Our proposed EAS model incorporates 2-phases. In …

Phamdb: A Web-Based Application For Building Phamerator Databases, James G. Lamine, Randall J. Dejong, Serita M. Nelesen

University Faculty Publications and Creative Works

PhamDB is a web application which creates databases of bacteriophage genes, grouped by gene similarity. It is backwards compatible with the existing Phamerator desktop software while providing an improved database creation workflow. Key features include a graphical user interface, validation of uploaded GenBank files, and abilities to import phages from existing databases, modify existing databases and queue multiple jobs. Availability and implementation: Source code and installation instructions for Linux, Windows and Mac OSX are freely available at https://github.com/jglamine/phage. PhamDB is also distributed as a docker image which can be managed via Kitematic. This docker image contains the application and all …

What Motivates High School Students To Take Precautions Against The Spread Of Influenza? A Data Science Approach To Latent Modeling Of Compliance With Preventative Practice, William L. Romine, Tanvi Banerjee, William R. Folk, Lloyd H. Barrow

Kno.e.sis Publications

– This study focuses on a central question: What key behavioral factors influence high school students’ compliance with preventative measures against the transmission of influenza? We use multilevel logistic regression to equate logit measures for eight precautions to students’ latent compliance levels on a common scale. Using linear regression, we explore the efficacy of knowledge of influenza, affective perceptions about influenza and its prevention, prior illness, and gender in predicting compliance. Hand washing and respiratory etiquette are the easiest precautions for students, and hand sanitizer use and keeping the hands away from the face are the most difficult. Perceptions of …

Rna-Seq Analysis Of Localized Mst1/Stk4 Expression In Prostate Cancer, Damien Ready

Master's Theses (2009 -)

The SKT4-encoded MST1 is a serine-threonine protein kinase and has known associations with many diseases and cancer.MST1 plays a critical component of the Hippo tumor suppressor pathway responsible for limiting cell division and promoting apoptosis.Loss of MST1 function is associated with poor prognostic outcomes for cancers, though the mechanism is not well understood.There is increasing evidence that dysregulation of MST1 can lead to castration-resistant prostate cancer (CRPCa), an aggressive cancer with limited treatment options.To better understand the mechanistic underpinnings of CRPCa progression, C4-2 prostate cancer cells were engineered toexpress MST1 protein directed to a particular subcellular region: membrane, nucleus, or …

Selfish Mutations: The Genetic Basis Of The Paternal Age Effect, Eoin C. Whelan

Biological Sciences Theses & Dissertations

As the mean age of childrearing grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father but have a deleterious effect in offspring.

I present a mathematical model to analyse the normal function of the stem cell compartment, which provides a framework for SSC renewal and accommodates differences between animal systems. In order to model the SSC mutation accumulation, a Markov chain …

Machine Learning Methods For Brain Image Analysis, Ahmed Fakhry

Computer Science Theses & Dissertations

Understanding how the brain functions and quantifying compound interactions between complex synaptic networks inside the brain remain some of the most challenging problems in neuroscience. Lack or abundance of data, shortage of manpower along with heterogeneity of data following from various species all served as an added complexity to the already perplexing problem. The ability to process vast amount of brain data need to be performed automatically, yet with an accuracy close to manual human-level performance. These automated methods essentially need to generalize well to be able to accommodate data from different species. Also, novel approaches and techniques are becoming …

A Computational Framework For Learning From Complex Data: Formulations, Algorithms, And Applications, Wenlu Zhang

Computer Science Theses & Dissertations

Many real-world processes are dynamically changing over time. As a consequence, the observed complex data generated by these processes also evolve smoothly. For example, in computational biology, the expression data matrices are evolving, since gene expression controls are deployed sequentially during development in many biological processes. Investigations into the spatial and temporal gene expression dynamics are essential for understanding the regulatory biology governing development. In this dissertation, I mainly focus on two types of complex data: genome-wide spatial gene expression patterns in the model organism fruit fly and Allen Brain Atlas mouse brain data. I provide a framework to explore …

An Informatics Research Agenda To Support Precision Medicine: Seven Key Areas., Jessica D Tenenbaum, Paul Avillach, Marge Benham-Hutchins, Matthew K Breitenstein, Erin L Crowgey, Mark A Hoffman, Xia Jiang, Subha Madhavan, John E Mattison, Radhakrishnan Nagarajan, Bisakha Ray, Dmitriy Shin, Shyam Visweswaran, Zhongming Zhao, Robert R Freimuth

Manuscripts, Articles, Book Chapters and Other Papers

The recent announcement of the Precision Medicine Initiative by President Obama has brought precision medicine (PM) to the forefront for healthcare providers, researchers, regulators, innovators, and funders alike. As technologies continue to evolve and datasets grow in magnitude, a strong computational infrastructure will be essential to realize PM's vision of improved healthcare derived from personal data. In addition, informatics research and innovation affords a tremendous opportunity to drive the science underlying PM. The informatics community must lead the development of technologies and methodologies that will increase the discovery and application of biomedical knowledge through close collaboration between researchers, clinicians, and …

Sequencing And Comparative Analysis Of De Novo Genome Assemblies Of Streptomyces Aureofaciens Atcc 10762, Julien S. Gradnigo

School of Biological Sciences: Dissertations, Theses, and Student Research

Streptomyces aureofaciens is a Gram-positive Actinomycete used for commercial antibiotic production. Although it has been the subject of many biochemical studies, no public genome resource was available prior to this project. To address this need, the genome of S. aureofaciens ATCC 10762 was sequenced using a combination of sequencing platforms (Illumina and 454-shotgun). Multiple de novo assembly methods (SGA, IDBA, Trinity, SOAPdenovo2, MIRA, Velvet and SPAdes) as well as combinations of these methods were assessed to determine which provided the most robust assembly. Combination strategies led to a consistent overestimation of the total genome size. Empirical data from targeted PCR …

Gene Set Enrichment And Projection: A Computational Tool For Knowledge Discovery In Transcriptomes, Karl Douglas Stamm

Dissertations (1934 -)

Explaining the mechanism behind a genetic disease involves two phases, collecting and analyzing data associated to the disease, then interpreting those data in the context of biological systems. The objective of this dissertation was to develop a method of integrating complementary datasets surrounding any single biological process, with the goal of presenting the response to a signal in terms of a set of downstream biological effects. This dissertation specifically tests the hypothesis that computational projection methods overlaid with domain expertise can direct research towards relevant systems-level signals underlying complex genetic disease. To this end, I developed a software algorithm named …

Research & Course-Based Applicatons Of The Ucsc Genome Browser, Ray A. Enke

Ray Enke Ph.D.

No abstract provided.

Phylotoast: Bioinformatics Tools For Species-Level Analysis And Visualization Of Complex Microbial Datasets, Shareef M. Dabdoub, Megan L. Fellows, Akshay D. Paropkari, Matthew R. Mason, Sarandeep S. Huja, Alexandra A. Tsigarida, Purnima S. Kumar

Oral Health Science Faculty Publications

The 16S rRNA gene is widely used for taxonomic profiling of microbial ecosystems; and recent advances in sequencing chemistry have allowed extremely large numbers of sequences to be generated from minimal amounts of biological samples. Analysis speed and resolution of data to species-level taxa are two important factors in large-scale explorations of complex microbiomes using 16S sequencing. We present here new software, Phylogenetic Tools for Analysis of Species-level Taxa (PhyloToAST), that completely integrates with the QIIME pipeline to improve analysis speed, reduce primer bias (requiring two sequencing primers), enhance species-level analysis, and add new visualization tools. The code …

Channa Striatus Tnfr-1: Molecular Cloning, Characterization And Gene Expression, Rajesh Palanisamy

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.

A Comparative Statement On Molecular Approach Of Large Hsps From Macrobrachium Rosenbergii, Mukesh Kumar Chaurasia

2nd International Conference of Fish & Shellfish Immunology

No abstract provided.

Intrinsic Disorder Where You Least Expect It: The Incidence And Functional Relevance Of Intrinsic Disorder In Enzymes And The Protein Data Bank, Shelly Deforte

USF Tampa Graduate Theses and Dissertations

Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) exist as interconverting conformational ensembles, without a single fixed three-dimensional structure in vivo. The focus in the literature up to this point has been primarily on IDPs that are mostly or entirely disordered. Therefore, we have an incomplete understanding of the incidence and functional relevance of IDPRs in proteins that have regions of both order and disorder. This work explores these populations, by examining IDPRs in the Protein Data Bank (PDB) and in enzymes. By applying disorder prediction methods combined with an analysis of missing regions in crystal structure data, …

Freshwater Metaviromics And Bacteriophages: A Current Assessment Of The State Of The Art In Relation To Bioinformatic Challenges, Katherine Bruder, Kema Malki, Alexandria Cooper, Emily Sible, Jason W. Shapiro, Siobhan C. Watkins, Catherine Putonti

Bioinformatics Faculty Publications

Advances in bioinformatics and sequencing technologies have allowed for the analysis of complex microbial communities at an unprecedented rate. While much focus is often placed on the cellular members of these communities, viruses play a pivotal role, particularly bacteria-infecting viruses (bacteriophages); phages mediate global biogeochemical processes and drive microbial evolution through bacterial grazing and horizontal gene transfer. Despite their importance and ubiquity in nature, very little is known about the diversity and structure of viral communities. Though the need for culture-based methods for viral identification has been somewhat circumvented through metagenomic techniques, the analysis of metaviromic data is marred with …

Exploration Of Chemical And Biological Management Strategies For Diaphorina Citri The Primary Vector Of Candidatus Liberibacter Asiaticus, Gretta Marie Sharp

Biology Theses

Diaphorina citri (Hemipteran: Psyllidae), the Asian citrus psyllid, is a phloem-feeding, invasive species endemic to southern Asia that was first identified in the United States in Florida in 1998. Since introduction, D. citri has spread across the major citrus growing regions of the United States. This is of great concern to the citrus industry because D. citri is the primary vector of Candidatus Liberibacter asiaticus the causal agent of Haunglongbing (HLB). Haunglongbing is the most economically devastating disease of citrus causing an estimated 8.92 billion dollars lost in revenue and 4.62 billion dollars lost in gross domestic product between 2006-2007 …

Measuring The Human Gut Microbiome: New Tools And Non Alcoholic Fatty Liver Disease, Ruth G. Wong

Electronic Thesis and Dissertation Repository

With the advent of next generation DNA and RNA sequencing, scientists can obtain a more comprehensive snapshot of the bacterial communities on the human body (known as the `human microbiome'), leading to information about the bacterial composition, what genes are present, and what proteins are produced. The scientific community is in a phase of developing the experiments and accompanying statistical techniques to investigate the mechanisms by which the human microbiome affects health and disease. In this thesis, I explore alternatives to the standard weighted and unweighted UniFrac distance metric that measure the difference between microbiome samples. These alternative weightings allow …

Identification, Characterization, And Life Cycle Of Intein-Associated Homing Endonucleases, Joshua J. Skydel

Honors Scholar Theses

Inteins are molecular parasites that have been identified in unicellular organisms from the three domains of life. The intein self-excises following translation of the host gene, and therefore incurs a fitness cost for its carrier. The symbiotic state of the intein to its host is dependent on the presence or absence of a homing endonuclease domain, which facilitates horizontal transfer of the molecule. Identification of this domain provides information on the evolutionary history of the intein, as well as patterns of horizontal gene transfer in microbial communities. I have therefore developed Hidden Markov Models (HMMs) to identify homing endonuclease domains …