Genomics Commons^™

Mucosal Genomics Implicate Lymphocyte Activation And Lipid Metabolism In Refractory Environmental Enteric Dysfunction, Najeeha Talat Iqbal, Najeeb Rahman, Kamran Sadiq, Zubair Ahmad, Romana Idress, Junaid Iqbal, Sheraz Ahmed, Aneeta Hotwani, Fayyaz Umrani, Sana Syed, Syed Asad Ali

Department of Paediatrics and Child Health

Background & aims: Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.
Methods: The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome was determined in 52 undernourished SEEM participants and 42 North American controls and celiac disease patients.
Results: After accounting for growth at study entry, circulating IGF-1 and ferritin predicted …

Up-Regulation Of Apoptotic- And Cell Survival-Related Gene Pathways Following Exposures Of Western Corn Rootworm To B. Thuringiensis Crystalline Pesticidal Proteins In Transgenic Maize Roots, Brad S. Coates, Emeline Deleury, Aaron J. Gassmann, Bruce E. Hibbard, Lance Meinke, Nicholas J. Miller, Jennifer L. Petzold-Maxwell, B. Wade French, Thomas W. Sappington, Blair D. Siegfried, Thomas Guillemaud

Department of Entomology: Faculty Publications

Background: Resistance of pest insect species to insecticides, including B. thuringiensis (Bt) pesticidal proteins expressed by transgenic plants, is a threat to global food security. Despite the western corn rootworm, Diabrotica virgifera virgifera, being a major pest of maize and having populations showing increasing levels of resistance to hybrids expressing Bt pesticidal proteins, the cell mechanisms leading to mortality are not fully understood.

Results: Twenty unique RNA-seq libraries from the Bt susceptible D. v. virgifera inbred line Ped12, representing all growth stages and a range of different adult and larval exposures, were assembled into a reference transcriptome. Ten-day exposures …

Genetic Diversity & Connectivity Of Chasmanthium Latifolium (Poaceae) In Pennsylvania & The Effect On Conservation Status Of A Rare Species, Jonathan D. Hayes

Honors Theses

Chasmanthium latifolium (Michx.) Yates (Poaceae) is a loosely colonial, rhizomatous, perennial grass species that lives in riparian habitats, making it fittingly referred to as river oats. Native to the southern Midwest and the eastern half of the United States, C. latifolium reaches the northeastern edge of its range in Pennsylvania. Within Pennsylvania, eleven extant C. latifolium populations are found along four waterways: the Monongahela River, the Susquehanna River, and two tributaries to the Susquehanna River. This limited state distribution exhibits an east-west disjunct distribution, where western populations are largely separated from eastern populations with one centrally located population. Between the …

Comparative Conservation Genomics Of A Suite Of Imperiled Freshwater Mussels, Scott C. Meyer

College of Graduate Studies: Theses & Dissertations

Maintenance of genetic diversity is a critical component to the management and recovery of imperiled species. By ensuring that a species’ genetic diversity is maintained, issues like inbreeding depression and loss of local adaptation can be prevented. However, the genetic diversity of many species are not well-characterized, and the factors that influence a species’ genetic diversity are often not well understood. In the case of imperiled unionid freshwater mussels, it is important to conduct conservation genetic assessments to aid in their management and preserve genetic diversity. This is the first study to conduct a comparative conservation genomic assessment for eight …

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 …

Novel Computational Methods For Cancer Genomics Data Analysis, Jinpeng Liu

Theses and Dissertations--Computer Science

Cancer is a genetic disease responsible for one in eight deaths worldwide. The advancement of next-generation sequencing (NGS) technology has revolutionized the cancer research, allowing comprehensively profiling the cancer genome at great resolution. Large-scale cancer genomics research has sparked the needs for efficient and accurate Bioinformatics methods to analyze the data. The research presented in this dissertation focuses on three areas in cancer genomics: cancer somatic mutation detection; cancer driver genes identification and transcriptome profiling on single-cell level.

NGS data analysis involves a series of complicated data transformation that convert raw sequencing data to the information that is interpretable by …

Applications Of Machine Learning In Microbial Forensics, Ryan B. Ghannam

Dissertations, Master's Theses and Master's Reports

Microbial ecosystems are complex, with hundreds of members interacting with each other and the environment. The intricate and hidden behaviors underlying these interactions make research questions challenging – but can be better understood through machine learning. However, most machine learning that is used in microbiome work is a black box form of investigation, where accurate predictions can be made, but the inner logic behind what is driving prediction is hidden behind nontransparent layers of complexity.

Accordingly, the goal of this dissertation is to provide an interpretable and in-depth machine learning approach to investigate microbial biogeography and to use micro-organisms as …

Metagenomic Identification And Classification Of The Mercury-Methylating Gene Hgca In Response To Water Table And Plant Functional Group Manipulations In Peat Soil, Madeline Peterson

Dissertations, Master's Theses and Master's Reports

Methyl-mercury (MeHg) is a potent neurotoxin that threatens the health of humans and wildlife alike. Climate warming threatens to shift regional precipitation and climate regimes in peatland environments, which could destabilize northern peatlands and accelerate both Hg release from soil and MeHg production. Peatlands are among the leading hotspots for MeHg, yet little is known about the community composition or functional relationship of mercury-methylating microbes in response to varying environmental conditions. The recognized mercury-methylating genes responsible for this activity are the obligatory gene pair hgcA and hgcB. Metagenomic data from the full-factorial peatland mesocosm experiment PEATcosm was obtained to …

Consensus Guidelines For Advancing Coral Holobiont Genome And Specimen Voucher Deposition, Christian R. Voolstra, Kate M. Quigley, Sarah W. Davies, John Everett Parkinson, Raquel S. Peixoto, Manuel Aranda, Andrew C. Baker, Adam R. Barno, Daniel J. Barshis, Francesca Benzoni, Victor Bonito, David G. Bourne, Carol Buitrago-López, Tom C.L. Bridge, Cheong Xin Chan, David J. Combosch, Jamie Craggs, Jörg C. Frommlet, Santiago Herrera, Andrea M. Quattrini, Till Röthig, James D. Reimer, Esther Rubio-Portillo, David J. Suggett, Helena Villela, Maren Ziegler, Michael Sweet

Biological Sciences Faculty Publications

Coral research is being ushered into the genomic era. To fully capitalize on the potential discoveries from this genomic revolution, the rapidly increasing number of high-quality genomes requires effective pairing with rigorous taxonomic characterizations of specimens and the contextualization of their ecological relevance. However, to date there is no formal framework that genomicists, taxonomists, and coral scientists can collectively use to systematically acquire and link these data. Spurred by the recently announced “Coral symbiosis sensitivity to environmental change hub” under the “Aquatic Symbiosis Genomics Project” - a collaboration between the Wellcome Sanger Institute and the Gordon and Betty Moore Foundation …

Lepidopteran Granivory Reduces Seed Counts In A Rare Species Of Riparian Scour Prairies, Cheyenne Moore, Angela J. Mcdonnell, Scott Schuette, Christopher T. Martine

Faculty Journal Articles

In Pennsylvania Baptisia australis var. australis is found along only four waterways: the Allegheny River, Youghiogheny River, Clarion River, and Red Bank Creek. Because of its limited distribution and small number of extant populations, the species is considered state-threatened in Pennsylvania. In addition, the riparian prairie habitat that Pennsylvania Baptisia australis var. australis is restricted to is also in decline and considered vulnerable. Because of these conservation concerns, insights into the natural history of the taxon in the state is valuable and will inform conservation efforts. Field surveys and fruit collections along the Allegheny River and herbarium collections were used …

Dietary Fiber Intake, The Gut Microbiome, And Chronic Systemic Inflammation In A Cohort Of Adult Men, Wenjie Ma, Long H. Nguyen, Mingyang Song, Dong D. Wang, Eric A. Franzosa, Yin Cao, Amit Joshi, David A. Drew, Raaj Mehta, Kerry L. Ivey, Lisa L. Strate, Edward L. Giovannucci, Jacques Izard, Wendy Garrett, Eric B. Rimm, Curtis Huttenhower, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Background: A higher intake of dietary fiber is associated with a decreased risk of chronic inflammatory diseases such as cardiovascular disease and inflammatory bowel disease. This may function in part due to abrogation of chronic systemic inflammation induced by factors such as dysbiotic gut communities. Data regarding the detailed influences of long-term and recent intake of differing dietary fiber sources on the human gut microbiome are lacking.

Methods: In a cohort of 307 generally healthy men, we examined gut microbiomes, profiled by shotgun metagenomic and metatranscriptomic sequencing, and long-term and recent dietary fiber intake in relation to plasma …

Post-Mortem Brain Nuclei Isolation For Single Nucleus Rna Sequencing, Charles J. Tran, Lin Y. Xie, Min Zhao, Edwin Jcg Van Den Oord, Karolina A. Aberg

Undergraduate Research Posters

Abstract

Post-Mortem Brain Nuclei Isolation for Single Nucleus RNA Sequencing

Charles Tran, Dept. of Biology, with Dr. Karolina Aberg, VCU School of Pharmacy

When tissue samples are studied in bulk without consideration for different cell proportions and types, results can be biased due to the attenuation of unique cellular expressions. In order to study cell type specific RNA expression profiles within tissue, single cell RNA sequencing (scRNA-seq) is used. For scRNA-seq studies it is critical to have intact cells. However, when investigating frozen post-mortem brain tissue, it is often challenging to isolate intact whole cells. An alternative solution is to …

Open Problems In Extracellular Rna Data Analysis: Insights From An Ercc Online Workshop, Roger P Alexander, Robert R Kitchen, Juan Pablo Tosar, Matthew Roth, Pieter Mestdagh, Klaas E A Max, Joel Rozowsky, Karolina Elżbieta Kaczor-Urbanowicz, Justin Chang, Leonora Balaj, Bojan Losic, Eric L Van Nostrand, Emily Laplante, Bogdan Mateescu, Brian S White, Rongshan Yu, Aleksander Milosavljevic, Gustavo Stolovitzky, Ryan M Spengler

Faculty, Staff and Students Publications

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19–20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop …

Investigation Into The Genetic Provenance Of Three Rare Plants With East-West Disjunction Patterns In Pennsylvania., Scott Schuette, Christopher T. Martine

Other Faculty Research and Publications

Rare plant conservation relies on an understanding of the natural history, biology and ecology, and real and potential threats to their populations to inform state regulations that serve to protect the species from extirpation. This work often involves extensive field surveys over several years to determine population sizes and whether those populations are seeing reductions in number of individuals necessary to maintain the genetic diversity within and between those populations. Species and populations with high genetic diversity are better equipped to withstand sudden changes to their habitats that derive from land use changes and changing climate. There are a variety …

Pharmacogenomics And Ssris Appropriateness In Older Community Dwelling African Americans, Wint War Phyo, Lana Sargent, Elvin T. Price

Graduate Research Posters

Background: Depressive and anxiety disorders are among the most common illnesses experienced by older adults (age > 60). The selective serotonin reuptake inhibitors (SSRIs) are preferred class of antidepressants for these disorders due to their high efficacy and safety profiles among older adults. However, SSRIs are metabolized by highly polymorphic cytochrome P450 enzymes, specifically CYP2D6 and CYP2C19. This can lead to variable dose-response outcomes, especially among older African American population.

Objective: Analyze the frequency of CYP2D6 and CYP2C19 polymorphisms in African American older adults who are taking SSRIs and identify potential inappropriate use of SSRIs in these older adults using the …

Initial And Advanced Stages Of Microbiota Establishment Within The Tsetse Fly, Miguel Eduardo Medina Munoz

Graduate Theses, Dissertations, and Problem Reports (ETD)

Symbiosis is a long-term physical association between two or more species, although little is known regarding its evolutionary origins, particularly at the genetic level. Tsetse flies are the vector of African trypanosomes, causative agents of Human and Animal African Trypanosomiases. Tsetse provide an ideal model for studying initial and advanced stages of symbiosis. Tsetse have a simple digestive tract microbiota primarily consisting of two bacteria; the ancient mutualist Wigglesworthia glossinidia and the recently acquired Sodalis glossinidius. This work presents a chronological study in evolutionary terms of the history of a microbial-insect association. First, I present concepts on symbiosis and …

Maternal Engineered Nanomaterial Inhalation Exposure: Cardiac Molecular Reprogramming In Progeny Through Epigenetic And Epitranscriptomic Mechanisms, Amina Kunovac

Graduate Theses, Dissertations, and Problem Reports (ETD)

Introduction: Nano-titanium dioxide (TiO₂), a prominently utilized engineered nanomaterial (ENM), is being employed for its physiochemical properties in several fields including the food industry, manufacturing, and biomedicine. As the prevalence of this ENM, and other particulate matter grows, so does the concern for antagonistic consequences on long-term heart function in vulnerable populations, which until now have not been investigated. Due to the reliance of the heart on the ATP generating capacity of mitochondria for contraction, understanding the role of mitochondrial bioenergetics and structure is pivotal in understanding the repercussions of particulate matter exposure during gestation. As the mass …

Effects Of 4-Methylcyclohexanemethanol On Stress Response Pathway Regulators, In Saccharomyces Cerevisiae, Suk Lan Ser

Graduate Theses, Dissertations, and Problem Reports (ETD)

Hydrotropes are small molecules capable of inducing liquid-liquid phase separation by altering the solubility and conformation states of organic compounds that are increasingly becoming important in organizing chemical reactions and regulating complexes. They prevent protein aggregation causing these proteins to form condensates. Mediator, a highly conserved multi-subunit complex, plays an important role in transcription. Med15, a subunit found within the tail domain of the Mediator complex, works with stress-induced transcription factors and is regulated by many kinases, including CDKs and the AMP kinase, Snf1. Living cells respond by changing molecular and cellular pathways when they are exposed to stressful conditions. …

Molecular And Genetic Studies On A Sipd/Ipad-Related Virulence Spike Protein From Immune-Suppressive Particles Of A Drosophila Parasitoid, Carlo Miguel A. Sevilla

Dissertations and Theses

Parasitoid wasps are effective biological control agents that have evolved intricate host immune suppression strategies to overcome host immune defenses. The most important anti-parasite defense mechanism is encapsulation, where the host’s blood cells surround the wasp egg. In the Drosophila/Leptopilina host-parasitoid system, extracellular vesicles (EVs) are oviposited along with the wasp egg. The EVs possess spikes and contain hundreds of proteins, some of which enable wasp eggs to escape encapsulation by changing the morphology and function of hemocytes, or killing them. Previous studies have identified an abundant surface/spike protein (SSp40) from Leptopilina heterotoma EVs. While p40, a predicted …

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 …