Genomics Commons^™

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

Development Of In-Silico Pipelines For Identification And Characterization Of Biomarker Panels And Therapeutic Interventions In Gastro-Intestinal (Gi) Cancers, Pranita Atri

Theses & Dissertations

Gastro-intestinal (GI) malignancies, including gastric, colorectal, and pancreatic cancers, have maintained their high overall mortality due to a lack of prognostic and diagnostic biomarkers and potential therapeutic modalities. While efforts have been made to improve both early detection and therapeutic interventions in these cancers, failure of conventional approaches have proven to be a big challenge, and alternate approaches are needed. Computational biology approaches owing to lesser time and more per target success rate offer a unique solution here. The current study explored the use of computational biology techniques to study the various aspects relating to GI malignancies. First, we sought …

Genomics, Exometabolomics, And Metabolic Probing Reveal Conserved Proteolytic Metabolism Of Thermoflexus Hugenholtzii And Three Candidate Species From China And Japan, Scott C. Thomas, Devon Payne, Kevin O. Tamadonfar, Cale O. Seymour, Jian Yu Jiao, Senthil K. Murugapiran, Dengxun Lai, Rebecca Lau, Benjamin P. Bowen, Leslie P. Silva, Katherine B. Louie, Marcel Huntemann, Alicia Clum, Alex Spunde, Manoj Pillay, Krishnaveni Palaniappan, Neha Varghese, Natalia Mikhailova, I. Min Chen, Dimitrios Stamatis, T. B.K. Reddy, Ronan O’Malley, Chris Daum, Nicole Shapiro, Natalia Ivanova, Nikos C. Kyrpides, Tanja Woyke, Emiley Eloe-Fadrosh, Trinity L. Hamilton, Paul Dijkstra, Brian P. Hedlund

Life Sciences Faculty Research

Thermoflexus hugenholtzii JAD2 , the only cultured representative of the Chloroflexota order Thermoflexales, is abundant in Great Boiling Spring (GBS), NV, United States, and close relatives inhabit geothermal systems globally. However, no defined medium exists for T. hugenholtzii JAD2 and no single carbon source is known to support its growth, leaving key knowledge gaps in its metabolism and nutritional needs. Here, we report comparative genomic analysis of the draft genome of T. hugenholtzii JAD2 and eight closely related metagenome-assembled genomes (MAGs) from geothermal sites in China, Japan, and the United States, representing “Candidatus Thermoflexus japonica,” “Candidatus Thermoflexus tengchongensis,” and “Candidatus …

Has Maize Overtaken Our Reality? A Personal Briefing, Biochemical Comparison, Agrigenomics, And History Of Maize, Nader Pahlevan

Honors Theses

Maize (Zea mays ssp. Mays) is a revolutionary cereal grain that has raced to the world’s most popular staple crop, transforming societies and impacting history. This paper aims to build and portray the story maize has created through its journey to world domination. The important details that encompass this literature are maize’s cultural significance in my life’s story, the comparison of various starches broken down into amylose and amylopectin ratios, a summative historical account on maize’s spread throughout numerous parts of the old world, and the genetical analysis of maize that explains the key features that have led …

Validation Of Anti-Oxidative Stress Genes From Genome-Wide Screening Of Escherichia Coli, Carson Ercanbrack

Chemistry & Biochemistry Undergraduate Honors Theses

The primary purpose of this project is to evaluate the genes that play a role in the oxidative stress response in Escherichia coli. In doing so, the entire genome of E. coli was subject to throughput in which individual genes were determined to have a role in the bacteria’s oxidative stress response. Moreover, this project focused on the validation of the genes that were able to pass the initial throughput stage. The genes were subject to two forms of validation. In the first validation technique, candidate genes were overexpressed and minimum inhibitory concentrations of hypochlorous acid were taken. Following, a …

Involvement Of The Ino80 Chromatin Remodeling Complex In Cell Division And Genomic Stability, Ethan Chen

Biomedical Engineering Undergraduate Honors Theses

Cell division is a vital biological process for growth and development in both single and multi-cellular organisms—whereby the cell must duplicate its organelles and genome in entirety and appropriately distribute the copied contents to the daughter cells. Cells undergo a cycle of two distinct phases: interphase and mitosis. During interphase, the cell replicates its genomic DNA (in the form of chromosomes) located within the nucleus. DNA replication is carried out in a euchromatin state, where the chromosome structure is loose and easily accessible by DNA polymerase and other replication enzymes. Upon the completion of replication, chromatin is condensed into highly …

Dynamics Of Hybrid Zones At A Continental Scale, Bradley T. Martin

Graduate Theses and Dissertations

Hybridization has traditionally been viewed as a happenstance that negatively impacts populations, but is now recognized as an important evolutionary mechanism that can substantially impact the evolutionary trajectories of gene pools, influence adaptive capacity, and contravene or reinforce divergence. Physiographic processes are important drivers of dispersal, alternately funneling populations into isolation, promoting divergence, or facilitating secondary contact of diverged populations, increasing the potential for hybridization. In North America, glacial-interglacial cycles and geomorphological changes have provided a dynamic backdrop over the last two million years that promoted such oscillations of population contraction and expansion. These biogeographic processes have resulted in regional …

The Diversity And Evolution Of Phenazine Biosynthesis Pathways In Enterobacterales, Christian Leise

Honors Theses

Enterobacterales is an order of Gram-negative bacteria that encompasses plant and animal pathogens and organisms of industrial importance. Some of these bacteria produce secondary metabolites classified as phenazines (Phz). Studies in other groups of microorganisms revealed that phenazines are redox-active and exhibit broad antibacterial, antifungal, and antiparasitic activity. Enterobacterales are known to produce phenazines, but details about the diversity, biochemistry, and function of phenazine metabolites in these organisms are missing. In this work, we screened the National Center for Biotechnology Information (NCBI) GenBank for genome sequences of phenazine-producing (Phz+) Enterobacterales. Additionally, genomes of Phz+ strains Pectobacterium carotovorum cc303 and …

Computational Approaches To Delineate Transcriptional And Functional Heterogeneity In Pancreatic Cancer, Sanjana Srinivasan

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is an incurable disease characterized by poor survival, dense desmoplastic stroma and activating mutations in KRAS (>90%). These tumors are highly complex ecosystems composed of molecularly distinct sub-populations that exhibit a spectrum of genetic features and associated phenotypes. Despite recent advances in the transcriptomic characterization of PDAC into at least two tumor subtypes, this alone has been insufficient to define more specific patterns of oncogenic dependency. To fully leverage advancements in next generation sequencing and functional genomics, we have sought to establish computational methodologies to aid in refined target discovery, and to develop a novel …

Mixture Model Approaches To Integrative Analysis Of Multi-Omics Data And Spatially Correlated Genomic Data, Ziqiao Wang

Dissertations and Theses (Open Access)

Integrative genomic data analysis is a powerful tool to study the complex biological processes behind a disease. Statistical methods can model the interrelationships of the involved gene activities through jointly analyzing multiple types of genomic data from different platforms (vertical integration), or improve the power of a study through aggregating the same type of genomic data across studies (horizontal integration). In this dissertation, we propose statistical methods and strategies for integrative multi-omics data in association analysis of disease phenotypes, with an emphasis on cancer applications.

We develop a new strategy based on horizontal integration by leveraging publicly available datasets into …

Understanding The Genetics Of Schizophrenia, Matthew Toohey

Thinking Matters Symposium

Schizophrenia has been considered heritable for a long time, but only with the advent of new technologies such as whole-genome sequencing and genome-wide association studies can we begin to identify specific molecular causes of schizophrenia. This poster will review some of the genetic variants that research groups have associated with schizophrenia. Current research has indicated that schizophrenia is a polygenic disease and has been linked to many genes. Some of these common risk variants are in protein coding sections of the DNA. These proteins are often linked to neurological development or immune system function. Other variants that have been associated …

307— Cooperation Of Selfish Genetic Elements In Stalk-Eyed Flies, Suhani Patel, Ben Mcpherson

GREAT Day Posters

SGEs are selfish genetic elements that increase the likelihood of their own transmission regardless of the host’s best interest. Transposable elements (TEs) and meiotic drivers are both types of SGEs. SGEs subsequently result in genetic conflict as they disrupt functional elements in the genome. We are working to better understand the cooperation of selfish genetic elements in Stalk-Eyed flies. Transposable elements are counteracted by small non-coding RNA molecules called piRNA. These RNA molecules work by reducing the expression of TEs by degrading TE RNA transcripts. Prior work in stalk-eyed flies has shown that TEs are expressed at a higher rate …

Annotation Of The Genome Of Drosophilia Ananassae, Landon Kehr

Celebration of Scholarship 2021

This project involves the use of software to annotate the genome of D. ananassae in collaboration with the Genomics Education Partnership. Annotations include coding regions and transcription start sites for specific genes that are homologous to D. melanogaster genes.

Comparative Genomics For D. Ananassae, Hailey Chang, Tia Watkins

Celebration of Scholarship 2021

The purpose of this project is to utilize comparative genomics tools to characterize specific genes in D. Ananassae. This is done in collaboration with the Genomics Education Partnership.

An Ensemble Of The Icluster Method To Analyze Longitudinal Lncrna Expression Data For Psoriasis Patients, Suyan Tian, Chi Wang

Internal Medicine Faculty Publications

BACKGROUND: Psoriasis is an immune-mediated, inflammatory disorder of the skin with chronic inflammation and hyper-proliferation of the epidermis. Since psoriasis has genetic components and the diseased tissue of psoriasis is very easily accessible, it is natural to use high-throughput technologies to characterize psoriasis and thus seek targeted therapies. Transcriptional profiles change correspondingly after an intervention. Unlike cross-sectional gene expression data, longitudinal gene expression data can capture the dynamic changes and thus facilitate causal inference.

METHODS: Using the iCluster method as a building block, an ensemble method was proposed and applied to a longitudinal gene expression dataset for psoriasis, with the …

A Whole-Genome Scan For Association With Invasion Success In The Fruit Fly Drosophila Suzukii Using Contrasts Of Allele Frequencies Corrected For Population Structure, Laure Olazcuaga, Anne Loiseau, Hugues Parrinello, Mathilde Paris, Antoine Fraimout, Christelle Guedot, Lauren M. Diepenbrock, Marc Kenis, Jinping Zhang, Xiao Chen, Nicolas Borowiec, Benoit Facon, Heidrun Vogt, Donald K. Price, Heiko Vogel, Benjamin Prud'homme, Arnaud Estoup, Mathieu Gautier

Life Sciences Faculty Research

Evidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here, we characterized the genome response of the spotted wing drosophila Drosophila suzukii during the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic …

The Giant Axolotl Genome Uncovers The Evolution, Scaling, And Transcriptional Control Of Complex Gene Loci, Siegfried Schloissnig, Akane Kawaguchi, Sergej Nowoshilow, Francisco Falcon, Leo Otsuki, Pietro Tardivo, Nataliya Timoshevskaya, Melissa C. Keinath, Jeramiah J. Smith, S. Randal Voss, Elly M. Tanaka

Biology Faculty Publications

Vertebrates harbor recognizably orthologous gene complements but vary 100-fold in genome size. How chromosomal organization scales with genome expansion is unclear, and how acute changes in gene regulation, as during axolotl limb regeneration, occur in the context of a vast genome has remained a riddle. Here, we describe the chromosome-scale assembly of the giant, 32 Gb axolotl genome. Hi-C contact data revealed the scaling properties of interphase and mitotic chromosome organization. Analysis of the assembly yielded understanding of the evolution of large, syntenic multigene clusters, including the Major Histocompatibility Complex (MHC) and the functional regulatory landscape of the Fibroblast Growth …

Nanopore Guided Regional Assembly, Eleni Adam, Desh Ranjan, Harold Riethman

College of Sciences Posters

The telomeres are the “caps” of the chromosomes and their vital role is to protect them. Possible telomere dysfunction caused by telomere rearrangements can be fatal for the cell and result in age-related diseases, including cancer. The telomeres and subtelomeres are regions that are hard to investigate. The current technology cannot provide their complete sequence, instead the DNA is given in multiple pieces. Current methods of assembling the pieces of these regions are not accurate enough due to the region’s high variability and complex repeated patterns. We propose a hybrid assembly method, the NPGREAT, which utilizes two of the latest …

Variation In The Genome And Transcriptome Associated With Beef Cattle Production And Investigation Of The Metabolic Consequences Of Beta-Adrenergic Agonist Supplementation, Renae L. Sieck

Department of Animal Science: Dissertations, Theses, and Student Research

Beta-adrenergic agonists (β-AA) are widely used supplements in livestock production to improve feed efficiency and increase lean muscle mass. Heat stress is one of the largest economic burdens to the livestock industry due to production efficiency losses and morbidity and mortality of animals. Both β-AA and catecholamines released in response to heat stress bind to β-adrenoceptors on the skeletal muscle cell surface to activate downstream signaling pathways. The purpose of this study was to determine if β-AA supplementation and heat stress have an additive effect on the skeletal muscle transcriptome. 3’ RNA sequencing of samples of the longissimus dorsi was …

Genomic Studies Of Beaf-32 In Drosophila, John Keller Mckowen Iii

LSU Doctoral Dissertations

Compared to humans, the model organism Drosophila melanogaster is particularly gene dense and encodes several insulator binding proteins (IBP) to aid in its genome organization. Our focus of research is a particular IBP, Boundary Element-Associated Factor of 32kD (BEAF). BEAF primarily binds near the promoters of constitutively active housekeeping genes. It is thought to help maintain the active state of these genes by preventing the spread of repressive chromatin. Additionally, the enhancer blocking activity of BEAF is thought to prevent aberrant activation or silencing of genes. BEAF appears to be ubiquitously expressed among cells and tissues, albeit at varying levels. …

Phenotypic Characters And Expression Of Cytokinin Oxidase 2 (Osckx2) Gene In Rice Genotypes With Enhanced Grain Filling Traits, Cielo Luz C. Mondejar, Maria Genaleen Q. Diaz, Teresita H. Borromeo, Tonette P. Laude, Arlen A. Dela Cruz, Roel Rodriguez Suralta

The Philippine Agricultural Scientist

Poor grain filling is still a major problem in rice production. Recent attention in crop varietal improvement is focused on heritable delayed foliar senescence, enhanced root system, and fast-synchronous grain filling pattern. Nine genotypes were characterized for these three enhanced grain-filling traits to determine the role of these traits on grain yield. Based on heritable delayed foliar senescence, NSIC Rc436 and NSIC Rc512 were characterized as Type A, while PSB Rc18 and NSIC Rc514 as Type B. These genotypes had a significantly higher yield than IR64, owing to their high spikelets number. Data suggested a positive correlation between the delayed …

16s Rrna Gene Sequence Analysis Of Acetic And Lactic Acid Bacteria Isolated From Philippine Sugarcane Wine (Basi) [Research Note], John Russel G. Sevilla, Michael Angelo S. Esteban, Honey Bhabes R. Iñigo, Audrey May V. Orillaza, Baby Richard R. Navarro

The Philippine Agricultural Scientist

Basi, a traditional sugarcane wine of the Philippines, was studied. Here, we used molecular- and cultural-based methods to isolate, identify and characterize acid-producing bacteria, specifically acetic and lactic acid bacteria, from basi. Acid producers were focused on owing to the rapid spoilage of basi via acidification with air exposure. Two strains each of acetic and lactic acid bacteria were isolated. DNA was extracted from these isolates. PCR-amplified DNA products were subjected to 16S rRNA gene sequencing. The sequences of the isolates were then aligned with BLAST database sequences and found to have high similarities to Acetobacter malorum (99%), …

Micro- And Macroevolution Of Drab Plumage Color In Birds, Rafael Marcondes

LSU Doctoral Dissertations

I address the evolution of drab bird colors at micro- and macroevolutionary scales. I use as a study system the Furnariida, a clade of >600 Neotropical passerine species that, despite tremendous ecological and morphological diversity, are colored almost exclusively in shades of brown and grey produced by melanin pigments.

In chapters two and three, I took a macroevolutionary approach and showed that (1) plumage colors in the Furnariida evolve at similar rates in a monochromatic clade, males of a dichromatic clade, and females of a dichromatic clade; (2) ventral plumage color evolves faster than dorsal; (3) bird species that occupy …

Synthesis, Structure-Activity Relationships, And Antiviral Activity Of Allosteric Inhibitors Of Flavivirus Ns2b-Ns3 Protease, Shenyou Nie, Yuan Yao, Fangrui Wu, Xiaowei Wu, Jidong Zhao, Yuanda Hua, Jingyu Wu, Tong Huo, Yi-Lun Lin, Alexander R Kneubehl, Megan B Vogt, Josephine Ferreon, Rebecca Rico-Hesse, Yongcheng Song

Faculty, Staff and Students Publications

Flaviviruses, including Zika, dengue and West Nile virus, are important human pathogens. The highly conserved NS2B-NS3 protease of Flavivirus is essential for viral replication and therefore a promising drug target. Through compound screen followed by medicinal chemistry studies, a novel series of 2,5,6-trisubstituted pyrazine compounds are found to be potent, allosteric inhibitors of Zika virus protease (ZVpro) with IC50 values as low as 130 nM. Their structure-activity relationships are discussed. The ZVpro inhibitors also inhibit homologous proteases of dengue and West Nile virus and their inhibitory activities are correlated. The most potent compounds 47 and 103 potently inhibited Zika virus …

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 …

Multimodal Single-Cell/Nucleus Rna Sequencing Data Analysis Uncovers Molecular Networks Between Disease-Associated Microglia And Astrocytes With Implications For Drug Repurposing In Alzheimer’S Disease, Jielin Xu, Pengyue Zhang, Yin Huang, Yadi Zhou, Yuan Hou, Lynn M. Bekris, Justin Lathia, Chien-Wei Chiang, Lang Li, Andrew A. Pieper, James B. Leverenz, Jeffrey Cummings, Feixiong Cheng

School of Medicine Faculty Research

Because disease-associated microglia (DAM) and disease-associated astrocytes (DAA) are involved in the pathophysiology of Alzheimer's disease (AD), we systematically identified molecular networks between DAM and DAA to uncover novel therapeutic targets for AD. Specifically, we develop a network-based methodology that leverages single-cell/nucleus RNA sequencing data from both transgenic mouse models and AD patient brains, as well as drug-target network, metaboliteenzyme associations, the human protein-protein interactome, and large-scale longitudinal patient data. Through this approach, we find both common and unique gene network regulators between DAM (i.e., PAK1, MAPK14, and CSF1R) and DAA (i.e., NFKB1, FOS, and JUN) that are significantly enriched …

Machine Learning Approaches For The Prediction Of Bone Mineral Density By Using Genomic And Phenotypic Data Of 5130 Older Men, Qing Wu, Fatma Nasoz, Jongyun Jung, Bibek Bhattarai, Mira V. Han, Robert A. Greenes, Kenneth G. Saag

School of Medicine Faculty Research

The study aimed to utilize machine learning (ML) approaches and genomic data to develop a prediction model for bone mineral density (BMD) and identify the best modeling approach for BMD prediction. The genomic and phenotypic data of Osteoporotic Fractures in Men Study (n = 5130) was analyzed. Genetic risk score (GRS) was calculated from 1103 associated SNPs for each participant after a comprehensive genotype imputation. Data were normalized and divided into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and linear regression were used to develop BMD prediction models separately. Ten-fold …

The Genomics Of Ecological Flexibility, Large Brains, And Long Lives In Capuchin Monkeys Revealed With Fecalfacs., Joseph D Orkin, Michael J Montague, Daniela Tejada-Martinez, Marc De Manuel, Javier Del Campo, Saul Cheves Hernandez, Anthony Di Fiore, Claudia Fontsere, Jason A Hodgson, Mareike C Janiak, Lukas F K Kuderna, Esther Lizano, Maria Pia Martin, Yoshihito Niimura, George H Perry, Carmen Soto Valverde, Jia Tang, Wesley C Warren, João Pedro De Magalhães, Shoji Kawamura, Tomàs Marquès-Bonet, Roman Krawetz, Amanda D Melin

Department of Biochemistry and Molecular Biology Faculty Papers

Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to …

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 …

Deep Learning For Multi-Tissue Cancer Classification Of Gene Expressions, Tarek Khorshed

Theses and Dissertations

We contribute in saving the lives of cancer patients through early detection and diagnosis, since one of the major challenges in cancer treatment is that patients are diagnosed at very late stages when appropriate medical interventions become less effective and full curative treatment is no longer achievable. Cancer classification using gene expressions is extremely challenging given the complexity and high dimensionality of the data. Current classification methods typically rely on samples collected from a single tissue type and perform a prerequisite of gene feature selection to avoid processing the full set of genes. These methods fall short in taking advantage …