Computational Biology Commons^™

Phenotypic And Transcriptomic Characterization Of Colonial Phase Variation In The Cholera Pathogen Reveals A Novel Smooth Biofilm-Defective Form, Bliss Nicole Lambert

LSU Doctoral Dissertations

Biofilm formation, through the production of Vibrio polysaccharide (VPS), greatly enhances the environmental fitness and pathogenic success of Vibrio cholerae. As a result of phase variation, V. cholerae can switch from a smooth form to rugose, whose cells produce excess VPS, resulting in highly structured biofilms and greater resistance to stress. To further characterize the reversible process of phase variation, we isolated three colonial lineages. Each lineage began with a smooth parent, N16961, and contained a rugose variant derived from the parent, N16961R, as well as a smooth revertant of the rugose, N16961SD. We found clear phenotypic and transcriptomic …

Red Panda: A Novel Method For Detecting Variation In Single-Cell Rna Sequencing, Adam Cornish

Theses & Dissertations

Single-cell sequencing enables the rapid acquisition of genomic and transcriptomic data from individual cells to better understand genetic diseases, such as cancer or autoimmune disorders, which are often affected by changes in rare cells. Currently, no existing software is aimed at identifying single nucleotide variations or micro (1-50bp) insertions and deletions in single-cell RNA sequencing (scRNA-seq) data. However, generating high quality data is vital to the study of the aforementioned diseases, among others. Our goal is to create such a tool and use in-house sequencing to validate its effectiveness. Our software employs the unique information found in scRNA-seq data to …

Physella Acuta, Comparative Immunology And Evolutionary Aspects Of Gastropod Immune Function, Jonathan H. Schultz

Biology ETDs

Gastropod immunobiology has benefitted from investigations focused on the planorbid snail Biomphalaria glabrata, intermediate host for the human parasite Schistosoma mansoni. Though such concentrated efforts have elucidated fascinating aspects of invertebrate immunity, they have not provided full knowledge regarding the evolution of immune function among other gastropod species. This dissertation presents the importance of making strategic choices regarding which organisms to select for comparative immunology. Herein, the choice was made to investigate the immunobiology of Physella acuta, a freshwater snail species of the Physidae, a sister family to Planorbidae to which B. glabrata belongs. Benefiting greatly from …

Acetylation Profiles Of Histone And Non-Histone Proteins In Breast Cancer, Alla Karpova

McKelvey School of Engineering Graduate Student Theses & Dissertations

This study evaluates the impact of protein acetylation on breast cancer gene expression and the regulation of metabolism. Acetylation is the second abundant post-translational modification after phosphorylation, regulating protein activity and function. The alterations in acetylation of both histone and non-histone proteins is known to be related to many human diseases, including cancer. Acetylation and deacetylation of histones is closely associated with the regulation of gene expression, while acetylation of non-histone proteins may have a broad effect on major cellular processes, such as proliferation, metabolism, cell cycle and apoptosis, imbalanced regulation of which is essential for cancer development. Therefore, it’s …

Improving Dbnsfp, Mingyao Lu

Dissertations and Theses (Open Access)

IMPROVING dbNSFP

Mingyao Lu, B.S.

Advisory Professor: Xiaoming Liu, Ph.D.

The analysis and interpretation of DNA variation are very important for the Whole Exome studies (WES). Genome research has focused on single nucleotide variants (SNVs). Since indels are as important as SNVs, especially indels in coding regions are often candidates of disease-causing variants, thus, it is necessary to expand the focus to include indel mutations.

The goal of my project is to provide an automatic annotation pipeline to the WES based disease studies project by extending the dbNSFP with a tool for automated indel annotation and deleteriousness prediction. The current …

Stochastic Difference Model For Evolutional Dynamics Of Large Antigen Repertoires In African Trypanosomes, Fan Yu

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Future Of Biodiversity Assessment: Using Environmental Dna And Next-Generation Sequencing To Characterize Biological Communities In The Central Highlands Of Arizona, Courtney Turner-Rathbone

Undergraduate Research Symposium - Prescott

Historically ecological surveys require significant man hours in the field, utilizing methods which can stress species being observed. In using environmental DNA (eDNA) gathered from air, soil, and water, traditional methods may be supplemented or reduced in order to more efficiently utilize funding and reduce or eliminate stress on surveyed species. Water was collected in replicates using aseptic technique from two different sites, 60 miles apart, along the Verde River. Samples were vacuum filtered within 24 hours through 0.45 μm cellulose nitrate (CN) filters to collect eDNA. DNA extraction from the filters was performed. The polymerase chain reaction (PCR) was …

Open-Source Tools For Dense Facial Tissue Depth Mapping (Ftdm) Of Computed Tomography Models, Terrie Simmons-Ehrhardt, Catyana Falsetti, Anthony B. Falsetti, Christopher J. Ehrhardt

Human Biology Open Access Pre-Prints

Computed tomography (CT) scans provide anthropologists with a resource to generate three- dimensional (3D) digital skeletal material to expand quantification methods and build more standardized reference collections. The ability to visualize and manipulate the bone and skin of the face simultaneously in a 3D digital environment introduces a new way for forensic facial approximation practitioners to access and study the face. Craniofacial relationships can be quantified with landmarks or with surface processing software that can quantify the geometric properties of the entire 3D facial surface. This paper describes tools for the generation of dense facial tissue depth maps (FTDMs) using …

Provenance And Risk In Transfer Of Biological Materials, Jane Nielsen, Tania M. Bubela, Don R C. Chalmers, Amber Johns, Linda Kahl, Joanne Kamens, Charles Lawson, John Liddicoat, Rebekah Mcwhirter, Ann Monott

Office of the Provost

Whereas biological materials were once transferred freely, there has been a marked shift in the formalisation of exchanges involving these materials, primarily through the use of Material Transfer Agreements (MTAs). This paper considers how risk aversion dominates MTA negotiations and the impact it may have on scientific progress. Risk aversion is often based on unwarranted fears of incurring liability through the use of a material or loss of control or missing out on commercialisation opportunities. Evidence to date has suggested that complexity tends to permeate even straightforward transactions despite extensive efforts to implement simple, standard MTAs. We argue that in …

Genetic Architecture Of Gene Expression Traits Across Diverse Populations, Lauren S. Mogil, Angela Andaleon, Alexa Badalamenti, Scott P. Dickinson, Xiuqing Guo, Jerome I. Rotter, W. C. Johnson, Hae Kyung Im, Yongmei Liu, Heather E. Wheeler

Bioinformatics Faculty Publications

For many complex traits, gene regulation is likely to play a crucial mechanistic role. How the genetic architectures of complex traits vary between populations and subsequent effects on genetic prediction are not well understood, in part due to the historical paucity of GWAS in populations of non-European ancestry. We used data from the MESA (Multi-Ethnic Study of Atherosclerosis) cohort to characterize the genetic architecture of gene expression within and between diverse populations. Genotype and monocyte gene expression were available in individuals with African American (AFA, n = 233), Hispanic (HIS, n = 352), and European (CAU, n = 578) ancestry. …

The Transcriptome Of The Bermuda Fireworm Odontosyllis Enopla (Annelida: Syllidae): A Unique Luciferase Gene Family And Putative Epitoky-Related Genes, Mercer R. Brugler, M. Teresa Aguado, Michael Tessler, Mark Siddall

Publications and Research

The Bermuda fireworm Odontosyllis enopla exhibits an extremely tight circalunar circadian behavior that results in an impressive bioluminescent mating swarm, thought to be due to a conventional luciferase-mediated oxidation of a light-emitting luciferin. In addition, the four eyes become hypertrophied and heavily pigmented, and the nephridial system is modified to store and release gametes and associated secretions. In an effort to elucidate transcripts related to bioluminescence, circadian or circalunar periodicity, as well as epitoky-related changes of the eyes and nephridial system, we examined the transcriptomic profile of three female O. enopladuring a bioluminescent swarm in Ferry Reach, Bermuda. …

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, …

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …

Quantitative Studies Of Amyloidogenic Protein Residue Interaction Networks And Abnormal Ammonia Metabolism In Neurotoxicity And Disease, Jeddidiah Griffin

Electronic Theses and Dissertations

Investigating similarities among neurological diseases can provide insight into disease processes. Two prominent commonalities of neurological diseases are the formation of amyloid deposits and altered ammonia and glutamate metabolism. Computational techniques were used to explore these processes in several neurological diseases. Residue interaction networks (RINs) abstract protein structure into a series of nodes (representing residues) and edges (representing connections between residues likely to interact). Analyzing the RINs of monomeric forms of amyloidogenic proteins for common network features revealed similarities not previously known. First, amyloidogenic variants of lysozyme were used to demonstrate the usefulness of RINs to the study of amyloidogenic …

Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez

KGI Theses and Dissertations

Prostate cancer (PCa) is the most common cancer of men in the United States and is third only to lung and colon as a cause of cancer death. Clinical behavior of the disease is variable and the combination of prostate-specific antigen (PSA) screening and Gleason score staging are currently the best available molecular and pathology tools to predict outcomes. Cancer biology research establishes microRNAs (miRNAs) as key molecular components in both normal and pathological states. Thus, elucidating miRNAs perturbed by genomic alterations will expand our understanding of the molecular taxonomy of PCa with the aim to complement current practices in …

Computational Analysis Of Papionini Evolution Using Alu Insertions, Vallmer Edward Jordan Ii

LSU Doctoral Dissertations

Alu elements are primate specific retrotransposons that have remained active throughout the course of primate evolution. As a result of this sustained mobilization. Alu elements are present in greater copy number in primate genomes than any other transposable element. An average of over one million Alu elements has been identified in every sequenced haplorrhine genome to date. These characteristics qualify Alu elements as ideal characters for studying evolutionary relationship among primates.

The increasing availability of whole genome sequencing data presents novel challenges and opportunities for comparative genomic analyses. Genomic data is now publicly available for most primate species. Such an …

Transcriptional Profiling Reveals Extraordinary Diversity Among Skeletal Muscle Tissues, Erin E. Terry, Xiping Zhang, Christy Hoffmann, Laura D. Hughes, Scott A. Lewis, Jiajia Li, Matthew J. Wallace, Lance A. Riley, Collin M. Douglas, Miguel A. Gutierrez-Monreal, Nicholas F. Lahens, Ming C. Gong, Francisco H. Andrade, Karyn A. Esser, Michael E. Hughes

Physiology Faculty Publications

Skeletal muscle comprises a family of diverse tissues with highly specialized functions. Many acquired diseases, including HIV and COPD, affect specific muscles while sparing others. Even monogenic muscular dystrophies selectively affect certain muscle groups. These observations suggest that factors intrinsic to muscle tissues influence their resistance to disease. Nevertheless, most studies have not addressed transcriptional diversity among skeletal muscles. Here we use RNAseq to profile mRNA expression in skeletal, smooth, and cardiac muscle tissues from mice and rats. Our data set, MuscleDB, reveals extensive transcriptional diversity, with greater than 50% of transcripts differentially expressed among skeletal muscle tissues. We detect …

Characterization Of An N-Terminal Non-Core Domain Of Rag1 Gene Disrupted Syrian Hamster Model Generated By Crispr Cas9, Jinxin Miao, Baoling Ying, Rong Li, Ann E. Tollefson, Jacqueline F. Spencer, William S.M. Wold, Seok-Hwan Song, Il-Keun Kong, Karoly Toth, Yaohe Wang, Zhongde Wang

Animal, Dairy, and Veterinary Science Faculty Publications

The accumulating evidence demonstrates that Syrian hamsters have advantages as models for various diseases. To develop a Syrian hamster (Mesocricetus auratus) model of human immunodeficiency caused by RAG1 gene mutations, we employed the CRISPR/Cas9 system and introduced an 86-nucleotide frameshift deletion in the hamster RAG1 gene encoding part of the N-terminal non-core domain of RAG1. Histological and immunohistochemical analyses demonstrated that these hamsters (referred herein as RAG1-86nt hamsters) had atrophic spleen and thymus, and developed significantly less white pulp and were almost completely devoid of splenic lymphoid follicles. The RAG1-nt86 hamsters had barely detectable CD3+ and CD4+ T cells. The …

Modeling And Analyzing An Optogenetic System For Photoactivatable Protein Dissociation, Anvin Thomas, James Schaff

Honors Scholar Theses

Computational modeling of cell-cell interactions can grant clues and can answer questions about an experiment, especially for observations about binding interactions and kinetics. This approach was used to investigate an interaction between a light-oxygen-voltage (LOV) domain and an engineered protein called Zdark (Zdk). The LOV domain is membrane-bound while Zdk is cytosolic. The LOV domain and Zdk bind strongly in dark (K_d 26.2 nM), and weakly upon exposure to blue light (K_d > 4 μM). Total internal reflection fluorescence (TIRF) images are acquired of Zdk, the fluorescent species bound to a mCherry tag, and the loss of fluorescence is …

Isolation, Sequencing, And Characterization Of Four Transmissible Antibiotic Resistance Plasmids Captured From Bacteria In Stream Sediments, Curtis J. Kapsak

Masters Theses, 2010-2019

Self-transmissible plasmids are key vectors in the transfer of resistance, catabolic, and other genes among bacteria native to environments such as streams and wetlands. The evolution of antibiotic resistance in particular is known to be powerfully affected by conjugative plasmid transfer due to the ease in which some plasmids can be horizontally transferred into a broad range of host bacteria and their ability to exchange mobile genetic elements that often contain antibiotic resistance genes.

In this study, we captured tetracycline resistance plasmids from stream sediments impacted by agricultural runoff. We selected for resistance plasmids using tetracycline, an antibiotic commonly used …

Characterizing Epigenetic Regulation In The Developing Chicken Retina, Bejan Abbas Rasoul

Masters Theses, 2010-2019

The retina, the sensory neuronal tissue within the eye, is composed of three layers of neuronal cells connected by two synaptic layers lining the inside of the anterior portion of the eye. Multipotent retinal precursor cells are genetically homogeneous and differentiate into mature retinal neurons due to differential gene expression. Differences in gene expression have been correlated with epigenetic modifications such as DNA methylation. DNA methylation of upstream regulatory elements is associated with transcriptional silencing of gene expression. Years of research in retinal development has identified the numerous genes expressed during the main steps of retinal development, however, it is …

Evolution Of Voltage-Gated Ion Channels, Kevin Gregory Bennett, Kevin Bennett

Master of Science in Integrative Biology Theses

Voltage-gated Ion Channels (VICs) form a superfamily of energy-independent membrane transporters that facilitate the transfer of charged sodium, calcium, and potassium ions across the cell membrane (Hodgkin & Huxley 1952). The channels contain a selective ion-conducting pore along with several other structural and gating features that come together to form a functional hetero- or homotetramer. A comprehensive phylogenetic study of all available proteins aimed at finding unknown distribution and illuminating evolutionary paths would be immensely useful in understanding relationships of structure, function, and organismal distribution. This phylogenetic analysis of VICs will be immensely useful in characterizing functional and structural distribution, …

Region Based Gene Expression Via Reanalysis Of Publicly Available Microarray Data Sets., Ernur Saka

Electronic Theses and Dissertations

A DNA microarray is a high-throughput technology used to identify relative gene expression. One of the most widely used platforms is the Affymetrix® GeneChip® technology which detects gene expression levels based on probe sets composed of a set of twenty-five nucleotide probes designed to hybridize with specific gene targets. Given a particular Affymetrix® GeneChip® platform, the design of the probes is fixed. However, the method of analysis is dynamic in nature due to the ability to annotate and group probes into uniquely defined groupings. This is particularly important since publicly available repositories of microarray datasets, such as ArrayExpress and NCBI’s …

Diversity, Structure And Sources Of Bacterial Communities In Earthworm Cocoons., Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez

Computational Biology Institute

Animals start interactions with the bacteria that will constitute their microbiomes at embryonic stage. After mating, earthworms produce cocoons externally which will be colonized with bacteria from their parents and the environment. Due to the key role bacterial symbionts play on earthworm fitness, it is important to study bacterial colonization during cocoon formation. Here we describe the cocoon microbiome of the earthworms Eisenia andrei and E. fetida, which included 275 and 176 bacterial species, respectively. They were dominated by three vertically-transmitted symbionts, Microbacteriaceae, Verminephrobacter and Ca. Nephrothrix, which accounted for 88% and 66% of the sequences respectively. Verminephrobacter and Ca. …

Efficient Reduced Bias Genetic Algorithm For Generic Community Detection Objectives, Aditya Karnam Gururaj Rao

Theses

The problem of community structure identification has been an extensively investigated area for biology, physics, social sciences, and computer science in recent years for studying the properties of networks representing complex relationships. Most traditional methods, such as K-means and hierarchical clustering, are based on the assumption that communities have spherical configurations. Lately, Genetic Algorithms (GA) are being utilized for efficient community detection without imposing sphericity. GAs are machine learning methods which mimic natural selection and scale with the complexity of the network. However, traditional GA approaches employ a representation method that dramatically increases the solution space to be searched by …

Glucocorticoids Modulate Gastrointestinal Microbiome In A Wild Bird., José C Noguera, Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez, Alberto Velando

Computational Biology Institute

It has recently been hypothesized that stress exposure (e.g. via glucocorticoid secretion) may dysregulate the bacterial gut microbiome, a crucial 'organ' in animal health. However, whether stress exposure (e.g. via glucocorticoid secretion) affects the bacterial gut microbiome of natural populations is unknown. We have experimentally altered the basal glucocorticoid level (corticosterone implants) in a wild avian species, the yellow-legged gull

Prediction Of Lncrna-Disease Associations Based On Inductive Matrix Completion, Chengqian Lu, Mengyun Yang, Feng Luo, Fang-Xiang Wu, Min Li, Yi Pan, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play pivotal roles in various biological processes. Mutations and dysregulations of lncRNAs are implicated in miscellaneous human diseases. Predicting lncRNA–disease associations is beneficial to disease diagnosis as well as treatment. Although many computational methods have been developed, precisely identifying lncRNA–disease associations, especially for novel lncRNAs, remains challenging.

Results: In this study, we propose a method (named SIMCLDA) for predicting potential lncRNA– disease associations based on inductive matrix completion. We compute Gaussian interaction profile kernel of lncRNAs from known lncRNA–disease interactions and functional similarity of diseases based on disease–gene and gene–gene onotology …

Copy Number Variation In The Porcine Genome Detected From Whole-Genome Sequence, Rebecca Anderson

Honors Program: Senior Projects (Public)

Copy number variations (CNVs) are large insertions, deletions, and duplications in the genome that vary between individuals in a species. These variations are known to impact a broad range of phenotypes from molecular-level traits to higher-order clinical phenotypes. CNVs have been linked to complex traits in humans such as autism, attention deficit hyperactivity disorder, nervous system disorders, and early-onset extreme obesity. In this study, whole-genome sequence was obtained from 72 founders of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC) in Clay Center, Nebraska. This included 24 boars (12 Duroc and 12 Landrace) and …

Gene-Based Association Study For Lipid Traits In Diverse Cohorts Implicates Bace1 And Sidt2 Regulation In Triglyceride Levels, Angela Andaleon, Lauren S. Mogil, Heather Wheeler

Bioinformatics Faculty Publications

Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted on lipid genetics, they mainly focus on Europeans and thus their transferability to diverse populations is unclear. We performed SNP- and gene-level genome-wide association studies (GWAS) of four lipid traits in cohorts from Nigeria and the Philippines and compared them to the results of larger, predominantly European meta-analyses. Two previously implicated loci met genome-wide significance in our SNP-level GWAS in the Nigerian cohort, rs34065661 in CETP associated with HDL cholesterol (P = 9.0 × 10⁻¹⁰) and …

Benchmark Evaluation Of True Single Molecular Sequencing To Determine Cystic Fibrosis Airway Microbiome Diversity, Andrea Hahn, Matthew L. Bendall, Keylie M. Gibson, Hollis Chaney, Iman Sami, Geovanny F. Perez, Anastassios C. Koumbourlis, Timothy A. Mccaffrey, Robert J. Freishtat, Keith A Crandall

Computational Biology Institute

Cystic fibrosis (CF) is an autosomal recessive disease associated with recurrent lung infections that can lead to morbidity and mortality. The impact of antibiotics for treatment of acute pulmonary exacerbations on the CF airway microbiome remains unclear with prior studies giving conflicting results and being limited by their use of 16S ribosomal RNA sequencing. Our primary objective was to validate the use of true single molecular sequencing (tSMS) and PathoScope in the analysis of the CF airway microbiome. Three control samples were created with differing amounts of Burkholderia cepacia, Pseudomonas aeruginosa, and Prevotella melaninogenica, three common bacteria found in cystic …