Computational Biology Commons^™

Sparse Forward-Backward Alignment For Sensitive Database Search With Small Memory And Time Requirements, David H. Rich

Graduate Student Theses, Dissertations, & Professional Papers

Sequence annotation is typically performed by aligning an unlabeled sequence to a collection of known sequences, with the aim of identifying non-random similarities. Given the broad diversity of new sequences and the considerable scale of modern sequence databases, there is significant tension between the competing needs for sensitivity and speed, with multiple tools displacing the venerable BLAST software suite on one axis or another. In recent years, alignment based on profile hidden Markov models (pHMMs) and associated probabilistic inference methods have demonstrated increased sensitivity due in part to consideration of the ensemble of all possible alignments between a query and …

Analysis Of Subtelomeric Rextal Assemblies Using Quast, Tunazzina Islam, Desh Ranjan, Mohammad Zubair, Eleanor Young, Ming Xiao, Harold Riethman

Computer Science Faculty Publications

Genomic regions of high segmental duplication content and/or structural variation have led to gaps and misassemblies in the human reference sequence, and are refractory to assembly from whole-genome short-read datasets. Human subtelomere regions are highly enriched in both segmental duplication content and structural variations, and as a consequence are both impossible to assemble accurately and highly variable from individual to individual. Recently, we developed a pipeline for improved region-specific assembly called Regional Extension of Assemblies Using Linked-Reads (REXTAL). In this study, we evaluate REXTAL and genome-wide assembly (Supernova) approaches on 10X Genomics linked-reads data sets partitioned and barcoded using the …

Applications Of Machine Learning In Microbial Forensics, Ryan B. Ghannam

Dissertations, Master's Theses and Master's Reports

Microbial ecosystems are complex, with hundreds of members interacting with each other and the environment. The intricate and hidden behaviors underlying these interactions make research questions challenging – but can be better understood through machine learning. However, most machine learning that is used in microbiome work is a black box form of investigation, where accurate predictions can be made, but the inner logic behind what is driving prediction is hidden behind nontransparent layers of complexity.

Accordingly, the goal of this dissertation is to provide an interpretable and in-depth machine learning approach to investigate microbial biogeography and to use micro-organisms as …

Leveraging Chemical And Computational Biology To Probe The Cellulose Synthase Complex, B. Kirtley Amos

Theses and Dissertations--Plant and Soil Sciences

Cellular expansion in plants is a complex process driven by the constraint of internal cellular turgor pressure by an expansible cell wall. The main structural element of the cell wall is cellulose. Cellulose is vital to plant fitness and the protein complex that creates it is an excellent target for small molecule inhibition to create herbicides. In the following thesis many small molecules (SMs) from a diverse library were screened in search of new cellulose biosynthesis inhibitors (CBI). Loss of cellular expansion was the primary phenotype used to search for putative CBIs. As such, this was approached in a forward …

Molecular Mechanisms Regulating Optic Fissure Fusion During Zebrafish Eye Development, Megan Weaver

Theses and Dissertations--Biology

Vertebrate retinal development requires timely and precise fusion of the optic fissure. Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed optic fissure fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a^-/- embryos fail to accumulate F-actin in the optic fissure prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a^-/- embryos. When examining the connection …

Leveraging Transcriptomic Approaches To Identify Differences In Genetic Programming Driving Two Distinct Wound Healing Mechanisms, Regeneration And Fibrosis, In Acomys And Mus, Shishir K. Biswas

Theses and Dissertations--Biology

Why can some animals and others cannot? This fundamental question has fueled scientists studying regeneration for hundreds of years since early observations in crayfish, salamanders and many other organisms. While most contemporary work in regeneration is done in a handful of species including salamanders, zebrafish and flatforms, these organisms lack a closely-related, non-regenerating sister species from which unique genetic differences can be identified. Additionally, while much has been learned from these organisms, they do not share fundamental biological traits with mammals (endothermy, metabolism and immune system) which limits the ability to translate this research for clinical medicine. To this end, …

Circadian Rhythmicity And Melatonin Sensitivity In The Human Gut Commensal Bacterium Klebsiella Aerogenes, Kinga Graniczkowska

Theses and Dissertations--Biology

While the expression of circadian rhythms is nearly universal among multicellular eukaryotic organisms, demonstration of this phenomenon in prokaryotes has been largely restricted to photosynthetic cyanobacteria until very recently. Further, growing interest in gastrointestinal microbiomes has revealed a complex temporal relationship between the gastrointestinal clock and the bacterial microbiome within. At least one member of the gut microbiome, Klebsiella (née Enterobacter) aerogenes, responds to the indoleamine hormone melatonin, secreted by the gastrointestinal system itself. Further research revealed that K. aerogenes also expresses a circadian rhythm in motility and gene expression that is temperature compensated. Although rhythmicity is unaltered …

Identification And Optimization Of Mirna Biomarkers For Body Mass Index (Bmi) Estimation In Forensic Samples, Jennifer J. Shealy

Master of Science in Forensic Science Directed Research Projects

DNA profiles do not provide as much evidentiary value when either all known samples can be excluded or when there is no known suspect. DNA phenotyping is a technique used for investigative purposes to predict externally visible characteristics (EVCs) based on specific markers found in the genome. Most phenotyping panels are currently restricted to markers stable over a lifetime within an individual and are not able to predict environmental or metabolic impacts on EVCs. It is known that miRNA expression levels change due to environmental and metabolic factors, such as BMI, and research has proven associations between circulating plasma miRNAs …

Statistical Methods In Genetic Studies, Cheng Gao

Dissertations, Master's Theses and Master's Reports

This dissertation includes three Chapters. A brief description of each chapter is organized as follows.

In Chapter 1, we proposed a new method, called MF-TOWmuT, for genome-wide association studies with multiple genetic variants and multiple phenotypes using family samples. MF-TOWmuT uses kinship matrix to account for sample relatedness. It is worth mentioning that in simulations, we considered hidden polygenic effects and varied the proportion of variance contributed by it to generate phenotypes. Simulation studies show that MF-TOWmuT can preserve the type I error rates and is more powerful than several existing methods in different simulation scenarios, MFTOWmuT is also quite …

Ensemble Protein Inference Evaluation, Kyle Lee Lucke

Graduate Student Theses, Dissertations, & Professional Papers

The Protein inference problem is becoming an increasingly important tool that aids in the characterization of complex proteomes and analysis of complex protein samples. In bottom-up shotgun proteomics experiments the metrics for evaluation (like AUC and calibration error) are based on an often imperfect target-decoy database. These metrics make the inherent assumption that all of the proteins in the target set are present in the sample being analyzed. In general, this is not the case, they are typically a mix of present and absent proteins. To objectively evaluate inference methods, protein standard datasets are used. These datasets are special in …

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 …