Computational Biology Commons^™

Genomic Tools And Models For Investigating The Role Of Germline Diversity In Mouse Antibody Repertoire Development., Justin T. Kos

Electronic Theses and Dissertations

Given the diversity and complexity within immunoglobulin (IG) loci, effective mouse models first require characterization of intra-strain differences and construction of high-quality reference assemblies for IG loci in several representative strains. To understand light chain germline diversity across biomedically significant mouse strains, we profiled the expressed IGK and IGL repertoires of 18 commonly used laboratory mouse strains using AIRR-seq. Across strains, we observed germline IGKV sequences shared by three different IGK haplotypes and a more conserved IGLV germline repertoire among common laboratory strains. Pacific Biosciences (PacBio) Single-Molecule Real-Time (SMRT) sequencing was used to sequence and assemble bacterial artificial chromosomes (BAC) …

Proteomic Analysis Of The Expression Of Masp1 Dragline Silk Protein In E. Coli, Sophie Rae Pazzo, Rajan Amit Patel, Kamrin Athwal, Edward Kim

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Comparative Modeling And Evolutionary Comparison Of Serine Protease, A Timber Rattlesnake Venom Protein, Qawer Ayaz

Theses

The aim of this study is to create a homology model of VG35 serine protease and evaluate the evolutionary comparison of secondary structure on basis of protein model using YASARA. This method was furthermore used to predict the potential epitopes which can help in the investigation of future studies.

The VG35 was used to run a BLAST search which gave most resembled serine protease of different species which was then translated and modeled in YASARA. The modeled protein data was then used to determine the secondary structure. This was then used for evolutionary comparison of all proteins to VG35. Then …

Meta-Analysis Of Two Rnaseq Datasets To Determine Diagnostic Biomarkers And Drug Target Candidates For Periodontitis, Carlos Moreno

Annual Research Symposium

No abstract provided.

The Low Abundance Of Cpg In The Sars-Cov-2 Genome Is Not An Evolutionarily Signature Of Zap, Ali Afrasiabi, Hamid Alinejad-Rokny, Azad Khosh, Mostafa Rahnama, Nigel Lovell, Zhenming Xu, Diako Ebrahimi

Plant Pathology Faculty Publications

The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG …

Identifying Epidermal Enriched Genes Required For Planarian Regeneration- Sp. Schmidtea Mediterranea, Pallob Barai

Theses and Dissertations--Biology

The outer epithelial layer covering an organism, commonly known as the epidermis, is crucial for maintaining homeostasis and for the wound healing processes after injury. The planarian epidermis allows flatworms to heal their wounds and virtually restore any missing tissues. Immediately after amputation, planarians contract their muscle and stretch their epidermis to heal the wound area. However, how the planarian epidermis coordinates with other tissues and mechanisms after the initial wound healing processes begins is not understood in detail. I hypothesized that epidermal cell stretching upon wound healing induces transcriptional changes that are required for effective regeneration. To test this …

Comparative Transcriptomic Analysis Of Cancer Testis Genes In Ovarian Cancer, Zayne Knuth

Dissertations, Master's Theses and Master's Reports

Cancer testis genes are common targets for the development of immunotherapy for cancer treatment. Ovarian cancer is one of the leading causes of death in women cancer patients. Cancer testis genes play a role in tumorigenesis, but it is not clear how these genes are activated. This study utilized differential expression analysis between The Cancer Genome Atlas (TCGA) ovarian cancer data, Genotype-Tissue Expression (GTEx) non-cancerous ovary and testis data, and cell line data to identify a list of cancer testis genes that have a novel expression profile. To identify ovarian cancer testis genes, we obtained normal ovary tissue data and …

Getting To The Root Cause: The Genetic Underpinnings Of Root System Architecture And Rhizodeposition In Sorghum, Farren Smith

Graduate Theses, Dissertations, and Problem Reports (ETD)

Plants are some of the most diverse organisms on earth, consisting of more than 350,000 different species. To understand the underlying processes that contributed to plant diversification, it is fundamental to identify the genetic and genomic components that facilitated various adaptations over evolutionary history. Most studies to date have focused on the underlying controls of above-ground traits such as grain and vegetation; however, little is known about the “hidden half” of plants. Root systems comprise half of the total plant structure and provide vital functions such as anchorage, resource acquisition, and storage of energy reserves. The execution of these key …

Human 5’-Tailed Mirtrons Are Processed By Rnasep, Mohammad Farid Zia

Dissertations

Approximately a thousand microRNAs (miRNAs) are documented from human cells. A third appear to transit non-canonical pathways that typically bypass processing by Drosha, the dedicated nuclear miRNA producing enzyme. The largest class of non-canonical miRNAs are mirtrons which eschew Drosha to mature through spliceosome activity. While mirtrons are found in several configurations, the vast majority of human mirtron species are 5’-tailed. For these mirtrons, a 3’ splice site defines the 3’ end of their hairpin precursor while a “tail” of variable length separates the 5’ base of the hairpin from the nearest splice site. How this tail is removed is …

Understanding Potassium Toxicity Stress Responses Of The Extremophyte Schrenkiella Parvula Using Systems Biology Approaches, Pramod Pantha

LSU Doctoral Dissertations

Schrenkiella parvula is an extremophyte model closely related to Arabidopsis thaliana and Brassica crops. Its natural habitat includes shores of saline lakes in the Irano-Turanian region. It has adapted to grow in soils rich in multiple salts including Na⁺ and K⁺. I have investigated the genetic basis for high K⁺ tolerance in plants using S. parvula as a stress tolerant model compared to the premier plant model, Arabidopsis thaliana which is highly sensitive to salt stresses using physiological, ionomic, transcriptomic, and metabolomic approaches. Under high K⁺ stress, root system architecture changes significantly compared to control …

Comparative Genomics Methods And Applications, Emily N. Alden

Biomedical Sciences ETDs

Virtually all fields of biology have benefited from the advancements in comparative genomics technologies, specifically in the study of evolution. In this dissertation I develop and use comparative genomic technologies to investigate the novel SARS-CoV-2 virus, assembly the first genome of the black lace domestic angelfish and identify germline genetic variants associated with altered breast cancer-specific survival. Our genome tiling array for the novel coronavirus presents a rapid and cost-effective method to sequence the entire viral genome and can be used to track the rapid evolution of viral variants in the population. The domestic angelfish is a member of the …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

Rare Variant Association Studies In Crohn’S Disease And Colorectal Cancer: Methods And Applications, Jiun-Sheng Chen

Dissertations and Theses (Open Access)

Genetic factors account for a substantial portion of Crohn’s disease and colorectal cancer (CRC) risk. Patients with Crohn’s disease, a condition that causes chronic inflammation of the gastrointestinal tract, are at increased risk of colorectal cancer morbidity and mortality. Genome-wide association studies using single marker approaches have identified loci responsible for these diseases, but disease susceptibility from rare variants is incompletely understood. This dissertation includes three chapters, two association studies for Crohn’s disease and CRC, and a statistical method to improve the power of statistical tests.

For Crohn’s disease, we performed targeted sequencing of 101 genes in 205 children with …

Stategra: Multi-Omics Data Integration - A Conceptual Scheme With A Bioinformatics Pipeline, Nuria Planell, Vincenzo Lagani, Patricia Sebastian-Leon, Frans Van Der Kloet, Ewoud Ewing, Nestoras Karathanasis, Arantxa Urdangarin, Imanol Arozarena, Maja Jagodic, Ioannis Tsamardinos, Sonia Tarazona, Ana Conesa, Jesper Tegner, David Gomez-Cabrero

Computational Medicine Center Faculty Papers

Technologies for profiling samples using different omics platforms have been at the forefront since the human genome project. Large-scale multi-omics data hold the promise of deciphering different regulatory layers. Yet, while there is a myriad of bioinformatics tools, each multi-omics analysis appears to start from scratch with an arbitrary decision over which tools to use and how to combine them. Therefore, it is an unmet need to conceptualize how to integrate such data and implement and validate pipelines in different cases. We have designed a conceptual framework (STATegra), aiming it to be as generic as possible for multi-omics analysis, combining …

Insights Into Leptopilina Spp. Immune-Suppressive Strategies Using Mixed-Omics And Molecular Approaches, Brian Wey

Dissertations, Theses, and Capstone Projects

Host-parasite interactions influence the biology of each over the course of evolution. Parasite success allows for the passage of potent virulence strategies from generation to generation. Host success passes stronger immunity and resistance strategies to the following generations as well. Only by studying both partners within their natural contexts can we begin to understand the relationship between the two and how immune mechanisms and virulence strategies interact as a molecular arms race.

In this work, we focus on a natural host-parasite pair, the Drosophila-Leptopilina model. Leptopilina species are parasites of several fruit fly species, including Drosophila melanogaster. This model …

Composition And Homology In The Taxonomic Classification Of Escherichia Coli, Tanya Irani

Theses and Dissertations (Comprehensive)

As new techniques have been introduced, specifically the possibility of complete genome sequencing, better methods of defining bacterial species have also been proposed. One of the most recently proposed methods, using bioinformatic techniques, is to calculate the average nucleotide identity (ANI) between the homologous genome segments of different isolates. Another method for species discrimination that has been tested successfully is the similarity of DNA compositional signatures. However, in a recent update, DNA signatures split the available Escherichia coli complete genomes into three groups. To check if this result was consistent with such genomes belonging to different species, we tested methods …

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 …

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 …

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 …

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 …

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 …

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 …

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, …

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 …

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 …

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 …

Chasing The Genetics Of Ascites In Broilers Using Whole Genome Resequencing, Alia Parveen

Graduate Theses and Dissertations

We are using whole genome resequencing to identify chromosomal regions associated with resistance or susceptibility to ascites, a form of pulmonary hypertension syndrome, meat-type chickens. Previous Genome Wide Association Studies (GWAS) based on Single Nucleotide Polymorphisms (SNPs) have identified regions on chromosomes 2, 9 and Z. Despite several GWAS and further genotyping, there are no reliable or potential markers for ascites phenotype. We have completed screening of Copy Number Variations (CNVs) and Single Nucleotide Polymorphisms in ascites resistant and susceptible birds from the relaxed, REL, line derived from a commercial elite broiler line. DNA samples from resistant and susceptible birds …