Genomics Commons^™

Integrative Analysis Of Multi-Omics Kinome Data And Virtual Screening Of Identified Targets With Pan-Cancer Application, Siddesh Southekal

Theses & Dissertations

Cancer is a heterogeneous disease characterized by the uncontrolled growth and dissemination of abnormal cells. Unfortunately, it is also challenging to treat due to the heterogeneous nature of the tumors and the lack of known drugs that are effective against all tumor subpopulations.

The human protein kinases represent an essential and diverse family of enzymes and are often dysregulated in cancer. The human kinome comprises only around 2% of all coding genes of the human genome but phosphorylates about 30% of cellular proteins critical for regulating various biological processes such as cell proliferation, cell cycle progression, apoptosis, motility, growth, differentiation, …

Rare And Low Frequency Genomic Variants Impacting Neuronal Functions Modify The Dup7q11.23 Phenotype, Farah Qaiser, Yue Yin, Carolyn B. Mervis, Colleen A. Morris, Bonita P. Klein-Tasman, Elaine Tam, Lucy R. Osborne, Ryan K.C. Yuen

School of Medicine Faculty Research

© 2021, The Author(s). Background: 7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers: nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD). Results: We identified three rare variants of potential clinical relevance for ASD: a 1q21.1 microdeletion (Dup7-non-ASD) and two deletions which …

Genomic Epidemiology Of Clostridium Difficile Colonization And Transmission In An Intensive Care Unit Cohort, Brianne Ciferri

Dissertations and Theses

Abstract

Genomic epidemiology of Clostridium difficile colonization and transmission in an intensive care unit cohort

by Brianne Ciferri, MPH

Advisor: C. Mary Schooling, PhD

Introduction: Clostridiodes difficile (C. difficile) is a leading cause of healthcare associated infections (HAI) in the United States and responsible for an estimated incidence of 223,900 cases and 12,800 deaths per year^1,2. C. difficile can cause gastrointestinal illness with symptoms ranging from mild diarrheal illness to a life-threatening condition. C. difficile is an opportunistic pathogen in which spores can live in an undisturbed dormant state within the intestinal tract and become …

Comparative Genome Analysis Of Fungal Antagonists Marinomonas Ostreistagni 398 And M. Spartinae 468., Jessie L. Fields

Honors Theses

Under certain conditions, the Spartina alterniflora and Juncus roemerianus grasses in marshes undergo progressive decline in an event known as Saltwater Marsh Dieback, which may be attributed to the presence of the plant pathogenic fungi Fusarium. The microbiomes of S. alterniflora and J. roemerianus from Deer Island, MS were characterized and Fusarium suppressing bacteria were identified. Among isolates capable of antagonizing Fusarium were Marinomonas ostreistagni 398 and M. spartinae 468. Despite the progress in understanding the diversity of Marinomonas, our ability to explain ecological, metabolic, and biochemical traits of marinomonads at the genomic sequence level remains limited. Analysis …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Phylogenomics Of Alligator Lizards Elucidate Diversification Patterns Across The Mexican Transition Zone And Support The Recognition Of A New Genus, Christopher Blair, Robert W. Bryson Jr, Uri O. García-Vázquez, Adrián Nieto-Montes De Oca, David Lazcano, John E. Mccormack, John Klicka

Publications and Research

Genomic data continue to advance our understanding of species limits and biogeographic patterns. However, there is still no consensus regarding appropriate methods of phylogenomic analysis that make the best use of these heterogeneous data sets. In this study, we used thousands of ultraconserved element (UCE) loci from alligator lizards in the genus Gerrhonotus to compare and contrast species trees inferred using multiple contemporary methods and provide a time frame for biological diversification across the Mexican Transition Zone (MTZ). Concatenated maximum likelihood (ML) and Bayesian analyses provided highly congruent results, with differences limited to poorly supported nodes. Similar topologies were inferred …

Genomics Of Postprandial Lipidomics In The Genetics Of Lipid-Lowering Drugs And Diet Network Study, Marguerite R. Irvin, May E. Montasser, Tobias Kind, Sili Fan, Dinesh K. Barupal, Amit Patki, Rikki M. Tanner, Nicole D. Armstrong, Kathleen A. Ryan, Steven A. Claas, Jeffrey R. O’Connell, Hemant K. Tiwari, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled …

Investigation Of Arabidopsis Extremophyte Relatives, Schrenkiella Parvula And Eutrema Salsugineum Reveals Different Roads Leading To Salt Stress Tolerance, Kieu-Nga Thi Tran

LSU Doctoral Dissertations

How plants adapt to salt stress has been a central question in plant biology for decades. Yet we have not been able to fully understand the molecular networks and genetic mechanisms underlying this complex trait. Most of the genetic work on salinity stress has focused on understanding salt stress responses in the leading, yet a salt-sensitive model Arabidopsis thaliana. With the recent availability of genomes for wild-relatives of A. thaliana, we can now investigate how naturally salt adapted plants may have evolved modified or novel molecular networks to adapt to salt stress. Therefore, my research utilizes a comparative …

Genetic Structuring And Community Assembly In Neotropical Birds, Oscar Johnson

LSU Doctoral Dissertations

The factors that influence how species form is of fundamental interest to biology. Under the framework of the speciation cycle, the process begins by population subdivision creating structured populations that then diverge until two new species form. Following speciation, however, continued divergence is necessary for these new species to be able to coexist without adverse interactions, known as the transition to secondary sympatry. At this point the speciation cycle is complete and the process can begin anew. Many of the factors influencing these processes remain poorly understood. Here, I explore the factors that influence speciation and community assembly in Neotropical …

Decoding The Equine Genome: Lessons From Encode, Sichong Peng, Jessica L. Petersen, Rebecca R. Bellone, Theodore S. Kalbfleisch, N. B. Kingsley, Alexa M. Barber, Eleonora Cappelletti, Elena Giulotto, Carrie J. Finno

Veterinary Science Faculty Publications

The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data …

Complete Genome Sequences Of Cluster A6 And Cluster G1 Mycobacterium Smegmatis Phages Hoot And Jolene, Jon Thompson, Asli Özdemir, Arsen M. Topchyan, Maxwell Torosian, Victoria Z. Thymianos, Angelica Eagle, Juliana Mccormick, Leon Kyle G. Boyles, Azucena A. Benito, Kurt Regner, Christy Strong, Philippos K. Tsourkas

Life Sciences Faculty Research

We present the complete genome sequences of Mycobacterium smegmatis phages Hoot and Jolene, isolated in Las Vegas, NV. The phages were isolated and annotated by students enrolled in an undergraduate research course at the University of Nevada, Las Vegas. Hoot is a cluster A6 mycobacteriophage, while Jolene is in cluster G1.

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 …

Determining Effective Drug Concentrations For Selection And Counterselection Genetics In Drosophila Melanogaster, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick, Koen J T Venken

Faculty, Staff and Students Publications

We recently integrated into fly genetics a set of four selection and two counterselection markers and their corresponding drugs that can be used individually or in combination. These markers eliminate the need to visually screen progeny. Before using these markers in new genetic backgrounds, effective selection/counterselection concentrations should be established for each marker/drug combination. This protocol describes how to set up, perform, and analyze a drug titration curve to determine the effective selection/counterselection drug concentrations for their corresponding markers. For complete details on the use and execution of this protocol, please refer to Matinyan et al., 2021.

Multiplexed Drug-Based Selection And Counterselection Genetic Manipulations In Drosophila, Nick Matinyan, Mansi S Karkhanis, Yezabel Gonzalez, Antrix Jain, Alexander Saltzman, Anna Malovannaya, Alejandro Sarrion-Perdigones, Herman A Dierick, Koen J T Venken

Faculty, Staff and Students Publications

The power of Drosophila melanogaster as a model system relies on tractable germline genetic manipulations. Despite Drosophila's expansive genetics toolbox, such manipulations are still accomplished one change at a time and depend predominantly on phenotypic screening. We describe a drug-based genetic platform consisting of four selection and two counterselection markers, eliminating the need to screen for modified progeny. These markers work reliably individually or in combination to produce specific genetic outcomes. We demonstrate three example applications of multiplexed drug-based genetics by generating (1) transgenic animals, expressing both components of binary overexpression systems in a single transgenesis step; (2) dual selectable …

Assesment Of Antibiotic Resistant Gene Expression In Clinical Isolates Of Pseudomonas Aeruginosa, Dustin Esmond

Biology Theses

Increasing prevalence of nosocomial infections by antimicrobial resistant pathogens resulting in higher mortality rates and financial burden is of great concern. Pseudomonas aeruginosa represents one of six highly virulent “ESKAPE” pathogens that exhibit considerable intrinsic drug resistance as well as mechanisms for acquiring further resistance. As many of these mechanisms are regulated through gene expression, we sought to identify regulatory strategies and patterns at play in 23 clinical isolates collected from Baku, Azerbaijan and Tyler, Texas, USA. Real-time quantitative polymerase chain reaction was performed on six gene targets implicated in resistance and contrasted with antibiotic phenotypes. We found AmpC cephalosporinase …

Foe To Friend: Parallel Domestication Of Ophiocordyceps From Fungal Parasite To Beneficial Symbiont In Cicadas, Jason Vailionis, Eric Rl Gordon, Chris Simon

University Scholar Projects

Nutritional symbioses are integral to the survival and diversity of many insects. The majority of herbivorous insects in the order Hemiptera possess stable, inherited symbionts that produce essential amino acids and vitamins. However, instability has been observed in cicadas, with one bacterial symbiont, Hodgkinia cicadicola, being repeatedly replaced by a new fungal symbiont, Ophiocordyceps. The fungal symbionts are thought to be derived from parasitic Ophiocordyceps species, but little is known about these parasitic ancestors or how the transition from parasite to mutualist occurs. We used a combination of targeted amplified genes and metagenomic sequencing to investigate the evolution …

Higher Entropy Observed In Sars-Cov-2 Genomes From The First Covid-19 Wave In Pakistan, Najia Karim Ghanchi, Asghar Nasir, Kiran I. Masood, Syed Hani Abidi, Syed Faisal Mahmood, Akber Kanji, Safina Abdul Razzak, Waqasuddin Khan, Saba Shahid, Maliha Yameen, Ali Raza, Javaria Ashraf, Zeeshan Ansar Ahmed, Mohammad Buksh Dharejo, Nazneen Islam, Zahra Hasan, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: We investigated the genome diversity of SARS-CoV-2 associated with the early COVID-19 period to investigate evolution of the virus in Pakistan.
Materials and methods: We studied ninety SARS-CoV-2 strains isolated between March and October 2020. Whole genome sequences from our laboratory and available genomes were used to investigate phylogeny, genetic variantion and mutation rates of SARS-CoV-2 strains in Pakistan. Site specific entropy analysis compared mutation rates between strains isolated before and after June 2020.
Results: In March, strains belonging to L, S, V and GH clades were observed but by October, only L and GH strains were present. The …

Insights Into Halophilic Microbial Adaptation: Analysis Of Integrons And Associated Genomic Structures And Characterization Of A Nitrilase In Hypersaline Environments, Sarah Sonbol

Theses and Dissertations

Hypersaline environments are extreme habitats that can be exploited as biotechnological resources. Here, we characterized a nitrilase (NitraS-ATII) isolated from Atlantis II Deep brine pool. It showed higher thermal stability and heavy metal tolerance compared to a closely related nitrilase.

We also studied integrons in halophiles and hypersaline environments. Integrons are genetic platforms in which an integron integrase (IntI) mediates the excision and integration of gene cassettes at specific recombination sites. In order to search for integrons in halophiles and hypersaline metagenomes, we used a PCR-based approach, in addition to different bioinformatics tools, mainly IntegronFinder.

We found that integrons and …

Artificial Image Objects For Classification Of Schizophrenia With Gwas-Selected Snvs And Convolutional Neural Network, Xiangning Chen, Daniel G. Chen, Zhongming Zhao, Justin Zhan, Changrong Ji, Jingchun Chen

School of Medicine Faculty Research

In this article, we propose a new approach to analyze large genomics data. We considered individual genetic variants as pixels in an image and transformed a collection of variants into an artificial image object (AIO), which could be classified as a regular image by CNN algorithms. Using schizophrenia as a case study, we demonstrate the principles and their applications with 3 datasets. With 4,096 SNVs, the CNN models achieved an accuracy of 0.678 ± 0.007 and an AUC of 0.738 ± 0.008 for the diagnosis phenotype. With 44,100 SNVs, the models achieved class-specific accuracies of 0.806 ± 0.032 and 0.820 …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

You Are What You Eat — Exploring The Microbiome Through Inquiry-Based Labs. Microbiome Lesson Plans, Karla S. Fuller

Open Educational Resources

If these commonly used spices have the ability to inhibit pathogenic bacterial growth, could they also potentially inhibit the growth of normal, harmless bacteria that live in your body? In this lab, we will test common bacteria for resistance to food additives.

Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche

Pharmaceutical Sciences (MS) Theses

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells (HMECs) were …

The Sulfur Microbial Diet And Risk Of Colorectal Cancer By Molecular Subtypes And Intratumoral Microbial Species In Adult Men, Daniel R. Sikavi, Long H. Nguyen, Koichiro Haruki, Tomotaka Ugai, Wenjie Ma, Dong D. Wang, Kelsey N. Thompson, Yan Yan, Tobyn Branck, Jeremy E. Wilkinson, Naohiko Akimoto, Rong Zhong, Mai Chan Lau, Kosuke Mima, Keisuke Kosumi, Teppei Morikawa, Eric B. Rimm, Wendy S. Garrett, Jacques Izard, Yin Cao, Mingyang Song, Curtis Huttenhower, Shuji Ogino, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Introduction: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.).

Methods: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012).

Results: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% …

Transcriptional Milestones In Dictyostelium Development, Mariko Katoh-Kurasawa, Karin Hrovatin, Shigenori Hirose, Amanda Webb, Hsing-I Ho, Blaž Zupan, Gad Shaulsky

Faculty, Staff and Students Publications

Dictyostelium development begins with single-cell starvation and ends with multicellular fruiting bodies. Developmental morphogenesis is accompanied by sweeping transcriptional changes, encompassing nearly half of the 13,000 genes in the genome. We performed time-series RNA-sequencing analyses of the wild type and 20 mutants to explore the relationships between transcription and morphogenesis. These strains show developmental arrest at different stages, accelerated development, or atypical morphologies. Considering eight major morphological transitions, we identified 1371 milestone genes whose expression changes sharply between consecutive transitions. We also identified 1099 genes as members of 21 regulons, which are groups of genes that remain coordinately regulated despite …

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 …

Human Population History At The Crossroads Of East And Southeast Asia Since 11,000 Years Ago, Tianyi Wang, Wei Wang, Guangmao Xie, Zhen Li, Xuechun Fan, Qingping Yang, Xichao Wu, Ling Qin, Fajun Li, Melinda A. Yang

Biology Faculty Publications

Past human genetic diversity and migration between southern China and Southeast Asia have not been well characterized, in part due to poor preservation of ancient DNA in hot and humid regions. We sequenced 31 ancient genomes from southern China (Guangxi and Fujian), including two ∼12,000- to 10,000-year-old individuals representing the oldest humans sequenced from southern China. We discovered a deeply diverged East Asian ancestry in the Guangxi region that persisted until at least 6,000 years ago. We found that ∼9,000- to 6,000-year-old Guangxi populations were a mixture of local ancestry, southern ancestry previously sampled in Fujian, and deep Asian ancestry …

Temperature Regulation Of Plant Hormone Signaling During Stress And Development, Christian Castroverde, Damaris Dina

Biology Faculty Publications

Global climate change has broad-ranging impacts on the natural environment and human civilization. Increasing average temperatures along with more frequent heat waves collectively have negative effects on cultivated crops in agricultural sectors and wild species in natural ecosystems. These aberrantly hot temperatures, together with cold stress, represent major abiotic stresses to plants. Molecular and physiological responses to high and low temperatures are intricately linked to the regulation of important plant hormones. In this review, we shall highlight our current understanding of how changing temperatures regulate plant hormone pathways during immunity, stress responses and development. This article will present an overview …

Evolution And Development Of The Seed Coat In Gymnosperms, Cecilia Zumajo

Dissertations, Theses, and Capstone Projects

Gymnosperms and angiosperms are the most abundant plant lineages on earth and constitute a turning point in the evolution of plants because they are at the origin of the seed, a key morphological and developmental novelty in the evolution of land plant. Although the morphological variation of the seed, across seed plants, may on its own, explain the complexity of this structure, the origin, and evolution are even more, the understanding of these topics is still under discussion. Evidence shows that previous studies have often lacked the component of gene expression, particularly in species that are not model species. The …

Genomic And Ecological Dimensions Of Malagasy Reptile And Amphibian Biodiversity, Arianna L. Kuhn

Dissertations, Theses, and Capstone Projects

A long history of isolation coupled with complex topographic and ecological landscapes makes Madagascar ideal for exploring the historical factors that have shaped patterns of population diversity and endemism. Many species-level studies have suggested Late Quaternary climate change may have influenced population dynamics in the tropics, but Madagascar’s ecologically unique biomes or individual species properties may have driven idiosyncratic responses to these shifts. Using community-scale population genetic data I implement a hierarchical approximate Bayesian computation (hABC) approach to evaluate the degree of synchronous population expansion during glacial cycles across herpetofaunal assemblages both within and across discrete biomes and taxonomic groups. …