Medicine and Health Sciences Commons^™

Effective Statistical Energy Function Based Protein Un/Structure Prediction, Avdesh Mishra

University of New Orleans Theses and Dissertations

Proteins are an important component of living organisms, composed of one or more polypeptide chains, each containing hundreds or even thousands of amino acids of 20 standard types. The structure of a protein from the sequence determines crucial functions of proteins such as initiating metabolic reactions, DNA replication, cell signaling, and transporting molecules. In the past, proteins were considered to always have a well-defined stable shape (structured proteins), however, it has recently been shown that there exist intrinsically disordered proteins (IDPs), which lack a fixed or ordered 3D structure, have dynamic characteristics and therefore, exist in multiple states. Based on …

Molecular Consequences Of High Taz Expression In Gliomas, Visweswaran Ravikumar

Dissertations & Theses (Open Access)

Diffuse high grade gliomas are complex and lethal neoplasms of the adult central nervous system that are driven by a range of genetic and epigenetic alterations. Molecular classification of these tumors has identified different transcriptional subtypes, the most notable being Proneural (PN) and Mesenchymal (MES) classes. The most aggressive forms of the disease have a Mesenchymal expression signature, with reported PN-to-MES transition occurring with tumor progression. Master regulatory analysis has identified the transcriptional co-activator TAZ (WWTR1) as a major driver of the MES transition. Overexpression of this single protein in glioma stem cells has been shown to drive a transition …

Association Of Copy Number Variations With Chronic Hepatitis B In Chinese Population, Fang Niu

Capstone Experience

With one third of the Hepatitis B virus (HBV) infection population of the world, chronic Hepatitis B (CHB) has become a top burden in China. CHB is a lifelong infection with HBV which can cause serious health problems, like cirrhosis, liver cancer or even death. HBV infection is known to result in various clinical conditions, including asymptomatic HBV carriers to chronic hepatitis and primary hepatocellular carcinoma. Several studies have shown that host genetic susceptibility could be an important factor that determines these various outcomes of HBV infection. Many Single Nucleotide Polymorphisms (SNPs) and Copy Number Variations (CNVs) have been associated …

Distinct Peripheral Blood Rna Responses To Salmonella In Pigs Differing In Salmonella Shedding Levels: Intersection Of Ifng, Tlr And Mirna Pathways, Ting-Hua Huang, Jolita J. Uthe, Shawn M. D. Bearson, Cumhur Yusuf Demirkale, Dan Nettleton, Susan Knetter, Curtis Christian, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Christopher K. Tuggle

Dan Nettleton

Transcriptomic analysis of the response to bacterial pathogens has been reported for several species, yet few studies have investigated the transcriptional differences in whole blood in subjects that differ in their disease response phenotypes. Salmonella species infect many vertebrate species, and pigs colonized with Salmonella enterica serovar Typhimurium (ST) are usually asymptomatic, making detection of these Salmonella-carrier pigs difficult. The variable fecal shedding of Salmonella is an important cause of foodborne illness and zoonotic disease. To investigate gene pathways and biomarkers associated with the variance in Salmonellashedding following experimental inoculation, we initiated the first analysis of the whole …

Unique Genome-Wide Transcriptome Profiles Of Chicken Macrophages Exposed To Salmonella-Derived Endotoxin, Ceren Ciraci, Christopher K. Tuggle, Michael J. Wannemeuhler, Dan Nettleton, Susan J. Lamont

Dan Nettleton

Background: Macrophages play essential roles in both innate and adaptive immune responses. Bacteria require endotoxin, a complex lipopolysaccharide, for outer membrane permeability and the host interprets endotoxin as a signal to initiate an innate immune response. The focus of this study is kinetic and global transcriptional analysis of the chicken macrophage response to in vitro stimulation with endotoxin from Salmonella typhimurium-798.

Results: The 38535-probeset Affymetrix GeneChip Chicken Genome array was used to profile transcriptional response to endotoxin 1, 2, 4, and 8 hours post stimulation (hps). Using a maximum FDR (False Discovery Rate) of 0.05 to declare genes as differentially …

Computational Genomic Models For Spatio-Temporal Investigation Of Early Lung Cancer Pathology, Smruthy Sivakumar

Dissertations & Theses (Open Access)

Lung cancer, of which non-small cell lung cancer (NSCLC) is the most common form, is the second most prevalent cancer and the leading cause of cancer-related deaths. NSCLCs primarily comprise adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). Advances in early detection and prevention have been limited by the lack of early-stage biomarkers and targets. A comprehensive molecular characterization of premalignant lesions and tumor-adjacent normal tissue can aid in better understanding NSCLC pathogenesis. However, these investigations are further challenged by limited tissue availability and low cellular fractions of detectable somatic mutations.

Therefore, there is a dearth of knowledge about the pathogenesis …

Ultramicrobacteria Genome Database Project, Abdullah A. Salim, Tien Tran, Andrew Putt, Terry C. Hazen

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Ultramicrobacteria (UMB) are a largely uncultured, globally abundant, and metabolically active group of bacteria. UMB have cell diameters ≤0.3μm, cell volumes ≤0.1 μm3, and small streamlined genomes. Recent findings indicate that UMB aid in bioremediation and nutrient cycling, but future investigations and comprehension of current findings are skewed by highly variable nomenclature and a lack of databases for functional, genomic, geochemical, or spatial data specific to candidate UMB. We aim to develop a user-friendly open-access database of various UMB candidates linked to an open-access online map where researchers can gather genomic, spatial, and geochemical data. Our comprehensive review of literature …

Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang

Biostatistics Faculty Publications

To analyze gene expression data with sophisticated grouping structures and to extract hidden patterns from such data, feature selection is of critical importance. It is well known that genes do not function in isolation but rather work together within various metabolic, regulatory, and signaling pathways. If the biological knowledge contained within these pathways is taken into account, the resulting method is a pathway-based algorithm. Studies have demonstrated that a pathway-based method usually outperforms its gene-based counterpart in which no biological knowledge is considered. In this article, a pathway-based feature selection is firstly divided into three major categories, namely, pathway-level selection, …

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential …

Exploring The Ipf Lung Through The Lens Of Single Cell Rna Sequencing, Taylor Adams, Jonas Schupp

Yale Day of Data

This poster illustrates the differences between the IPF disease-specific variety of lung macrophages and the two varieties of macrophages known to reside in the normal human lung.

Cyclin C: The Story Of A Non-Cycling Cyclin., Jan Ježek, Daniel G J Smethurst, David C Stieg, Z A C Kiss, Sara E Hanley, Vidyaramanan Ganesan, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit …

Overview Of Direct Thrombin Inhibitors For Use In Staphylococcus Aereus Infections, Joseph C. Risler

Honors Undergraduate Theses

The pathogenicity and intractable nature of the microorganism Staphylococcus aureus (SA) has been long documented and highlighted by many health care agencies, with emphasis on its ability to exploit the human coagulation system to deadly effect. Two drugs from a class of inhibitors known as Direct Thrombin Inhibitors (DTI) have been shown to have a substantial effect on the enzyme secreted by SA known as Staphylocoagulase (SC), but up until now the application of this potential treatment has been limited. This paper strives to supply an overview of these clinical studies and propose a novel protocol for testing DTI's on …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …