Computational Biology Commons^™

Single-Fluorophore Sensors For Mechanical Force In Living Cells, Sarah Kricheff

Honors Scholar Theses

Mechanotransduction is the process by which a mechanical stimulus is converted to a cellular signal. This process is heavily influential of cell morphology, differentiation, and behavior. However, altered levels of mechanical stimuli are also found in many pathological contexts. For example, cancerous cells have stiffer surrounding tissue than healthy cells, and research suggests that this alters cell behavior and promotes metastasis. Despite these findings, the cellular processes behind these signaling alterations remain widely unknown. Understanding these cascades is critical, as involved proteins can give us a deeper understanding of the role of mechanotransduction, and certain proteins can potentially be targeted …

An Examination Of The Influence Of Multi-Scale Processes And Connectivity On The Population And Assemblage Dynamics Of Headwater Fishes, Josh P. Hubbell

Dissertations

Typified by their branching pattern, headwaters are numerically abundant as the density of these habitats increases with increasing distance from the base of a dendritic river system. Connectivity among headwaters is complex, resulting in the spatial isolation of populations. Headwater specialists have evolved a suite of traits that permit these species to permanently reside within these habitats. The spatial configuration and connectivity of headwaters has repercussions for metapopulations and meta-assemblages. I investigated how multi-scale processes and connectivity influenced the patch occupancy, coexistence, movement ecology, population structure, and gene flow of headwater specialists. In chapter two, I used occupancy modeling to …

Gene Set Testing By Distance Correlation, Sho-Hsien Su

Graduate Theses and Dissertations

Pathways are the functional building blocks of complex diseases such as cancers. Pathway-level studies may provide insights on some important biological processes. Gene set test is an important tool to study the differential expression of a gene set between two groups, e.g., cancer vs normal. The differential expression of a gene set could be due to the difference in mean, variability, or both. However, most existing gene set tests only target the mean difference but overlook other types of differential expression. In this thesis, we propose to use the recently developed distance correlation for gene set testing. To assess the …

Investigation Of Sulfur Cycling In Marine Sponge Cinachyrella Spp. From A South Florida Reef, Shelby K. Cain

All HCAS Student Capstones, Theses, and Dissertations

Symbionts within marine sponges are actively participating in the biogeochemical cycles. Among them, the role of symbiont microbes in the sulfur cycle remains a mystery. This study measured the abundance of microbes within the genus Cinachyrella before and after exposure to hydrogen sulfide. A four-part study was conducted: a) five-hour drop experiments, b) vertical distribution experiments, c) five-hour uptake experiments, and d) long-term exposure experiments. The five-hour drop experiment utilized a microsensor to measure sulfide levels, which was lowered 1.0 mm every thirty minutes for a total of 5 hours. Three trials were performed, each with one sponge and a …

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

Decoding The Evolutionary Response To Prostate Cancer Therapy Using Plasma Genome Sequencing, Naveen Ramesh

Dissertations and Theses (Open Access)

Investigating genome evolution in response to therapy is difficult in human tissue samples due to the difficulty in accessing metastatic tumor sites and logistical challenges of collecting longitudinal samples. To overcome these issues, we developed an unbiased whole-genome plasma DNA sequencing approach called PEGASUS that concurrently measures genomic copy number and exome mutations from archival cryostored plasma samples. This approach was applied to study longitudinal blood plasma samples from prostate cancer patients. A molecular characterization of archival plasma DNA from 233 patients and genomic profiling of 101 patients identified clinical correlations of aneuploid plasma DNA profiles with poor survival, increased …

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations and Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

Polerovirus Genomic Variation And Mechanisms Of Silencing Suppression By P0 Protein, Natalie M. Holste

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

The family Luteoviridae consists of three genera: Luteovirus, Enamovirus, and Polerovirus. The genus Polerovirus contains 32 virus species. All are transmitted by aphids and can infect a wide variety of crops from cereals and wheat to cucurbits and peppers. However, little is known about how this wide range of hosts and vectors developed. In poleroviruses, aphid transmission and virion formation is mediated by the coat protein read-through domain (CPRT) while silencing suppression and phloem limitation is mediated by Protein 0 (P0)—a protein unique to poleroviruses. P0 gives poleroviruses a great advantage amongst plant viruses and diversifies polerovirus species, but the …

Pathway-Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Jem Bagchee-Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan

Biochemistry Publications

No abstract provided.

Quantifying Structure And Variation In Complex Phylogenetic Data, Genevieve Geraldine Mount

LSU Doctoral Dissertations

Identifying the source and structure of variation in nature is crucial to understanding fundamental aspects of evolution. Despite a recent plethora of genetic and morphological data, many interesting questions about the relationships between different groups remain unresolved. My dissertation evaluates three approaches for identifying and quantifying the variation within phylogenetic datasets. Characterizing variation within datasets and across analytical methods gives insight into biologically interesting characters, unusual evolutionary processes, and areas for model improvement.

Network-based community detection approaches offer a powerful tool to describe variation in phylogenetic signal across the genome (i.e., gene tree variation). In Chapter 2, I investigate the …

Not Withering On The Evolutionary Vine: Systematic Revision Of The Brown Vine Snake (Reptilia: Squamata: Oxybelis) From Its Northern Distribution, Robert C. Jadin, Christopher Blair, Sarah A. Orlofske, Michael J. Jowers, Gilson A. Rivas, Laurie J. Vitt, Julie M. Ray, Eric N. Smith, John C. Murphy

Publications and Research

The genus Oxybelis currently is composed of four taxa despite numerous studies suggesting and describing multiple taxa within the O. aeneus complex. Here, we utilize a multilocus molecular dataset (i.e. cyt b, ND4, 12S, 16S, cmos, PRLR, 3663 bp) to conduct phylogenetic analyses to assess the evolutionary history of Oxybelis. Our molecular analyses find three major lineages of Oxybelis (i.e. O. aeneus complex, O. brevirostris, O. fulgidus complex) with a sister relationship between O. brevirostris and the O. aeneus complex to the exclusion of the O. fulgidus complex. More specifically, O. aeneus appears to harbor at least …

Machine Learning Applications For Drug Repurposing, Hansaim Lim

Dissertations, Theses, and Capstone Projects

The cost of bringing a drug to market is astounding and the failure rate is intimidating. Drug discovery has been of limited success under the conventional reductionist model of one-drug-one-gene-one-disease paradigm, where a single disease-associated gene is identified and a molecular binder to the specific target is subsequently designed. Under the simplistic paradigm of drug discovery, a drug molecule is assumed to interact only with the intended on-target. However, small molecular drugs often interact with multiple targets, and those off-target interactions are not considered under the conventional paradigm. As a result, drug-induced side effects and adverse reactions are often neglected …

Linking Crude Oil And Dispersant Effects To Gene Expression Of Marine Sponge Cinachyrella, Yvain Desplat

All HCAS Student Capstones, Theses, and Dissertations

Because of their filter-feeding lifestyle, sponges (Phylum Porifera) have shown to be bio-accumulators of heavy metals, and bio-monitors for polychlorobiphenyl (PCB) contaminants. Furthermore, marine sponges have been shown to be regulators of reef ecosystems by fulfilling many ecological functions. However, very little is known about their behavior in the face of environmental changes. Consequently, our lab has developed the reef sponge Cinachyrella spp. as novel experimental model. We have designed an experiment to study the effects of WAF (Water Accommodated Fraction), Corexit 9500 dispersant, and CE-WAF (Chemically Enhanced Water Accommodated Fraction)mixtures, in an effort to mimic the conditions of the …

Identification Of Trim24 Domain Essentiality In Primary Trim24coe Carcinosarcoma Cell Lines, Cem Dede

Dissertations and Theses (Open Access)

Regulation of transcriptional control is a critical feature for organismal development and survival. Because of its effects on chromatin-controlled expression, disruptions of this delicately tuned mechanism are an important factor in development of tumorigenesis. Therefore, there is a growing interest in targeting these control mechanisms for their potential therapeutic values.

Our lab previously discovered the epigenetic regulator function of Tripartite motif protein 24 (TRIM24) through its H3K4me0 and H3K23ac dual histone signature reader function, its negative regulatory effect on the p53 tumor suppressor, in addition to its shown oncogenic driving capacity on immortalized mammary epithelial cells when overexpressed. Although TRIM24 …

Statistical Methods For Resolving Intratumor Heterogeneity With Single-Cell Dna Sequencing, Alexander Davis

Dissertations and Theses (Open Access)

Tumor cells have heterogeneous genotypes, which drives progression and treatment resistance. Such genetic intratumor heterogeneity plays a role in the process of clonal evolution that underlies tumor progression and treatment resistance. Single-cell DNA sequencing is a promising experimental method for studying intratumor heterogeneity, but brings unique statistical challenges in interpreting the resulting data. Researchers lack methods to determine whether sufficiently many cells have been sampled from a tumor. In addition, there are no proven computational methods for determining the ploidy of a cell, a necessary step in the determination of copy number. In this work, software for calculating probabilities from …

Metabolic Network Analysis Of Filamentous Cyanobacteria, Daniel Alexis Norena-Caro

LSU Doctoral Dissertations

Cyanobacteria were the first organisms to use oxygenic photosynthesis, converting CO₂ into useful organic chemicals. However, the chemical industry has historically relied on fossil raw materials to produce organic precursors, which has contributed to global warming. Thus, cyanobacteria have emerged as sustainable stakeholders for biotechnological production. The filamentous cyanobacterium Anabaena sp. UTEX 2576 can metabolize multiple sources of Nitrogen and was studied as a platform for biotechnological production of high-value chemicals (i.e., pigments, antioxidants, vitamins and secondary metabolites). From a Chemical engineering perspective, the biomass generation in this organism was thoroughly studied by interpreting the cell as a microbial …

The Evolution Of Bivalve Shell Matrix Proteins, Mark Ira Duhon Ii

LSU Doctoral Dissertations

This dissertation focuses on the molecular underpinnings surrounding the evolution of the biomineralized shells of marine bivalves. Bivalve molluscs synthesize remarkably complex shells from calcium carbonate and an organic matrix of proteins secreted from the dorsal edge of the mantle. Molecular analyses of shell matrix proteins (SMPs) have suggested high rates of gene turnover despite the conserved nature of the shell itself. Here, I used proteomic and transcriptomic data to identify the SMPs and other biomineralization proteins from seven bivalve species that diverged 3-513 Mya. Contrary to previous studies that identified only a few shared biomineralization transcripts across the Bivalvia, …

Statistical Inference Of Adaptation At Multiple Genomic Scales Using Supervised Classification And A Hidden Markov Model, Lauren A. Sugden

Biology and Medicine Through Mathematics Conference

No abstract provided.

Comparative Analysis Of Metabolic Pathways Of Bacteria Used In Fermented Food, Keanu Hoang, Kiran Bastola

Theses/Capstones/Creative Projects

This study presents a novel methodology for analyzing metabolic pathways. Utilizing KEGG REST API through a Biopython package and file parser, data about whether or not a bacteria has an enzyme or not was extracted. The results found that differences in metabolic pathway enrichment values follow along the lines of genera and pathway type. In particular, bacteria found in food spoilage and commercial nitrogen fixing products had high values of enrichment.

Meta-Analysis Of Biological Research Literature, Evan Suggs

Honors Theses

Comparative studies have been powerful tools in generating a broad understanding about the evolution of animal social systems but they currently rely on the slow, manual process of reading thousands of abstracts and papers from research databases. A web application was created for researchers conducting a comparative survey, in order to speed up their research. This web application automates the retrieval of research papers and their selection process. Using previously obtained data sets on the orders Artiodacytla and Lagomorph, a machine learning application was created to classify the papers. These techniques and tools should greatly increase the speed at which …

Identification And Analysis Of Feather Degrading Bacteria: A Search For Keratinase Genes, Nehal Navali

Honors Scholar Theses

Over two million tons of feather waste is generated annually by the poultry industry, the majority of which goes into landfills due to the difficulty of degrading its major component keratin. Although a portion of feather waste is eliminated via incineration or chemical treatment, the use of Feather Degrading Bacteria (FDB) has been proposed as a cheap and eco-friendly alternative. FDBs have been consistently isolated from the feather microbiome of birds and contain genes coding for the specialized protein keratinase which is able to degrade feathers. By doing so, feather waste, which is rich in nutrients, can be repurposed as …

Evolutionary And Ecological Determinism Of Host Specificity In Arthropod Parasites, Joseph Levey

UCARE: Research Products

Understanding why some diseases infect more species than others is crucial for predicting where and when disease will spread, which can inform the management of wildlife, agriculture, and human health. Currently, large scale patterns of host-parasite dynamics are being studied to understand where to look for and how to manage emerging human diseases (Leroy 2005; Benelli 2018). Previous research has used the Global Mammal Parasite Database (GMPD) to look at host breadth—the number and diversity of species a pathogen can infect—for various groups of parasites, e.g. helminths, arthropods, fungi, etc., from a host-centric perspective (Stephens et al. 2017; Park et …

Ensemble Modeling Of Auditory Streaming Reveals Potential Sources Of Bistability Across The Perceptual Hierarchy, David F. Little, Joel S. Snyder, Mounya Elhilali

Psychology Faculty Research

Perceptual bistability—the spontaneous, irregular fluctuation of perception between two interpretations of a stimulus—occurs when observing a large variety of ambiguous stimulus configurations. This phenomenon has the potential to serve as a tool for, among other things, understanding how function varies across individuals due to the large individual differences that manifest during perceptual bistability. Yet it remains difficult to interpret the functional processes at work, without knowing where bistability arises during perception. In this study we explore the hypothesis that bistability originates from multiple sources distributed across the perceptual hierarchy. We develop a hierarchical model of auditory processing comprised of three …

Dugesia Japonica Is The Best Suited Of Three Planarian Species For High-Throughput Toxicology Screening, Danielle Ireland, Veronica Bochenek , '22, Daniel Chaiken , '20, Christina Rabeler, Sumi Onoe , '21, Ameet Soni, Eva-Maria S. Collins

Biology Faculty Works

High-throughput screening (HTS) using new approach methods is revolutionizing toxicology. Asexual freshwater planarians are a promising invertebrate model for neurotoxicity HTS because their diverse behaviors can be used as quantitative readouts of neuronal function. Currently, three planarian species are commonly used in toxicology research: Dugesia japonica, Schmidtea mediterranea, and Girardia tigrina. However, only D. japonica has been demonstrated to be suitable for HTS. Here, we assess the two other species for HTS suitability by direct comparison with D. japonica. Through quantitative assessments of morphology and multiple behaviors, we assayed the effects of 4 common solvents (DMSO, …

Synthesis And Molecular Mechanics Study Of Platinum Triamine Complex With N-Acetyl-L-Methionine And Guanosine 5’Monophosphate, Nitin Tanajirao Katare

Masters Theses & Specialist Projects

Cisplatin and its analogues have been used and tested over decades for cancer treatment, but because of the serious side effects, it is important to find ways to overcome those side effect by synthesizing a novel platinum molecule. We have synthesized triamine complex and conducted its reaction with biomolecules such as 5’GMP and Methionine in the lab as well as conducted molecular mechanics (MM). MM methods are used for predicting and designing new structures and properties, and to model geometries of small molecules. MM and dynamics calculations have been used to study the 9 Ethylguanine and N-Ac-Lmethionine complexes with platinum …

On The Distribution Of Genetic Variation In Ecological Communities, Isaac Overcast

Dissertations, Theses, and Capstone Projects

Biodiversity in ecological communities is structured hierarchically across spatial and temporal scales. Many open questions remain as to how this structure accumulates. For example, what are the relative contributions of dispersal versus in situ speciation? Or, how important are stochastic drift versus deterministic processes? Up to this point, these questions have been investigated by isolated disciplines (e.g. macroecology, comparative phylogeography, macroevolution) using tools and data that tend to focus on only one axis of community scale data (e.g. phylogenies, relative abundances, and/or trait information). Yet we know that there are feedbacks among processes that respond on short, medium, and long …

Machine Learning Prediction Of Glioblastoma Patient One-Year Survival, Andrew Du '20, Warren Mcgee, Jane Y. Wu

Student Publications & Research

Glioblastoma (GBM) is a grade IV astrocytoma formed primarily from cancerous astrocytes and sustained by intense angiogenesis. GBM often causes non-specific symptoms, creating difficulty for diagnosis. This study aimed to utilize machine learning techniques to provide an accurate one-year survival prognosis for GBM patients using clinical and genomic data from the Chinese Glioma Genome Atlas. Logistic regression (LR), support vector machines (SVM), random forest (RF), and ensemble models were used to identify and select predictors for GBM survival and to classify patients into those with an overall survival (OS) of less than one year and one year or greater. With …

Mathematical Models Of Cellular Signaling And Supramolecular Self-Assembly, Pratip Rana

Theses and Dissertations

Synthetic biologists endeavor to predict how the increasing complexity of multi-step signaling cascades impacts the fidelity of molecular signaling, whereby cellular state information is often transmitted with proteins diffusing by a pseudo-one-dimensional stochastic process. We address this problem by using a one-dimensional drift-diffusion model to derive an approximate lower bound on the degree of facilitation needed to achieve single-bit informational efficiency in signaling cascades as a function of their length. We find that a universal curve of the Shannon-Hartley form describes the information transmitted by a signaling chain of arbitrary length and depends upon only a small number of physically …

The Host Gatekeeper: Using The Flagellar Pathway To Understand Symbiont Host Adaptation, Adam R. Pollio

Graduate Theses, Dissertations, and Problem Reports (ETD)

The acquisition of microbial partners is a strategy used by a diverse group of arthropods to overcome ecological barriers that might normally make certain niches uninhabitable. The unique phylogenetic opportunities attainable from the natural experiment of the Sodalis-allied clade allow for better understanding of how molecular structures evolve through time. Here, we focus on the evolution of the flagellar synthesis pathway, due to its complexity and ability to diverge in response to ecological pressures. We used this molecular pathway and natural experiment to show that normal evolutionary outcomes associated with symbiosis (i.e., genome reduction) do not explain the predicted conservation …

Evaluation Of The Performance Of Probabilistic Genotyping Software On Complex Mixture Samples, Kristen Newland

Graduate Theses, Dissertations, and Problem Reports (ETD)

Probabilistic genotyping systems use sophisticated algorithms to aid DNA analysts with complex mixture interpretation. These systems are used to generate a likelihood ration (LR) which is used to provide the analyst with the statistical weight of the match between an evidence profile and a known contributor. Complex mixtures occur from samples consisting of more than two contributors and samples that have experienced degradation or consist of low template quantity.

This study was performed to compare the performance of three mixture analysis software tools on the same set of samples to determine the capabilities of each software, false inclusions, and false …