Genomics Commons^™

Characterization Of Microrna Expression In Neuron-Enriched Extracellular Vesicles During Early Life, Allison Molen

Theses and Dissertations

Extracellular vesicles (EVs) are membrane-bound sacs released by cells that carry molecular cargo reflective of their cell of origin. EVs enriched using L1 cell adhesion molecule (L1CAM) as a marker of putative neuronal origin can cross the blood–brain barrier and provide a minimally invasive window into brain-related processes. Exosomal microRNA (miRNA) regulate gene expression and have been implicated in psychiatric disorders, including major depressive disorder (MDD). However, measuring and analyzing miRNA from L1CAM-positive EVs presents substantial analytical challenges due to low abundance and sparse detection across samples.

Plasma samples from participants recruited through the Mid-Atlantic Twin Registry (MATR) were used …

Identifying Rna Splicing Changes During Alcohol Withdrawal Using An Optimized Rna-Seq Analysis Pipeline, Yasaswi Veera, Luana Martins De Carvalho, Amy Lasek

Undergraduate Research Posters

Alcohol use disorder (AUD) causes long-lasting changes in brain gene expression and RNA splicing, particularly in the ventral hippocampus. This study analyzes RNA-Seq data from rats exposed to chronic alcohol and withdrawal to identify transcript-level and splicing alterations. An optimized RNA-Seq pipeline using STAR, FeatureCounts, edgeR, and WGCNA improved efficiency by 25-40% while maintaining consistency across 25 datasets. Results reveal changes in neural signaling and stress-response pathways associated with withdrawal. This work provides both biological insight into AUD and a reproducible computational framework for transcriptomic analysis.

Analysis Of Differential Gene Expression In Androgen-Independent Clones Derived From The Mycap Pca Cell Line, Jessie L. Tignor, Melanie Sinanian, Richard Inho Joh, David Gewirtz, Jason Reed

Undergraduate Research Posters

Androgen deprivation therapy (ADT) is a primary treatment strategy for prostate cancer (PCa), yet many tumors eventually develop androgen independence, leading to treatment resistance. To investigate the molecular changes underlying this transition, we analyzed differential gene expression in four androgen-independent (AI) clones derived from the Myc-CaP prostate cancer cell line using RNA sequencing. Gene expression profiles were compared to the parental Myc-CaP line, and differentially expressed genes (DEGs) were identified using DESeq2 and edgeR. The AI clones exhibited significant downregulation of senescence-associated genes, including Ezh2 and lamin B1, suggesting a loss of senescence-related chromatin repression. Additionally, upregulation of Wnt pathway …

A Standardized Pipeline For Isolation And Assembly Of Genomes From Symbiotic Bacteria In Whole Louse Genomic Sequence Data., Mohammad Mikail I. Bala

Theses and Dissertations

Many insects are known to harbour intracellular and heritable bacteria (endosymbionts), which provide their hosts with adaptive traits. Whole insect gDNA shotgun sequencing projects often sequence the genome of endosymbiont, in addition to the insect’s genome. There are approximately 600 whole genome shotgun libraries from insects available on the public repository (NCBI), which can be mined to obtain endosymbiont genomes. The assembly and annotation of endosymbiont genomes can contribute towards the exploration of their role as obligate symbiotic partners. However, de novo assembly of an endosymbiont genome, continues to be challenging, when the host and/or enteric bacterial gDNA is present …

Genomic Comparison Of Dba/2j And C57bl/6j Strains Of Mus Musculus And Best Practice Of Genome Alignment For Bioinformatics Analyses, Dustin J. Zeliff

Theses and Dissertations

Alcohol use disorder is known to have significant genetic components that contribute to an individual’s susceptibility to the disease. Mouse models are commonly used to study the mechanisms underlying alcohol use disorder, with C57BL/6J (B6) and DBA/2J (D2) being two of the more prominently used inbred strains. Research in the Miles Laboratory has used these two strains, and genetic panels of mice derived from them, to identify potential genes associated with variance in ethanol-related behaviors using quantitative trait loci (QTL) analysis. For example, Ninein (Nin) was identified as a potential candidate gene for the anxiolytic effects of ethanol, discovered because …

Novel Feature Evaluation In Ultra-High Dimensional Right-Censored Data, With Applications To Head And Neck Cancer, Atika Farzana Urmi

Graduate Research Posters

Background: Head and neck cancer is the 6th most common cancer worldwide with an expected 1.08 million new cases each year. Such cancer data are ultra-high dimensional with thousands of clinical features and gene expressions, making it challenging for the traditional analytical tools to extract the potential biomarker for the cancer survival and control false discoveries. In addition, presence of heavy censoring can affect the screening procedures based on Kaplan-Meier (K-M) survival estimates.

Aim: To propose a model free, ultra-high dimensional feature screening method with two-dimensional survival outcome allowing false discovery rate (FDR) control.

Method: 516 primary tumor patients with …

Incorporating A Developmental Perspective Into Gene Identification Models For Alcohol Use Behaviors, Nathaniel S. Thomas

Theses and Dissertations

Frequent alcohol use can lead to alcohol use disorder, which accounts for three million deaths and over 133 million life years lost to disability and death worldwide per year. Alcohol use behaviors unfold across development, beginning with initiation of drinking and progressing through various escalating stages of use. Alcohol use behaviors are also under genetic influence. Genome-wide association represents the state-of-the-science statistical methodology for identifying genes associated with alcohol use outcomes. However, contemporary genome-wide association study (GWAS) methods typically do not account for variability in genetic effects throughout development. In this project, I applied novel multivariate genomic methods to combine …

Evaluating Population Genetic Structure And Potential Genomic Signals Of Natural Selection In A Migratory Songbird (Protonotaria Citrea), Tyler A. Hohenstein

Theses and Dissertations

In this study I attempted to further resolve the population genetic structure in the Prothonotary Warbler (Protonotaria citrea), and conducted an outlier SNP analysis and exploratory gene ontology analysis to investigate potential ongoing natural selection in the species. This analysis of population structure confirms previous work by DeSaix et al. (2019), where weak population structure was observed between eastern sites along the Atlantic Coastal Plain, and western sites in the Mississippi Alluvial Valley, possibly due to a genetic discontinuity across the Appalachian Mountains. I conducted two forms of outlier SNP analyses, a principal component analysis (PCA)-based approach to identify SNPs …

Examination Of Common And Rare Variant Genetic Architecture Of Psychiatric Disorders, Mohammad Ahangari

Theses and Dissertations

Psychiatric disorders are often heterogenous in their manifestation and genome-wide association studies have identified many common risk variants involved in their polygenic architectures with varying degrees of pleiotropy. In recent years, large-scale biobanks have also begun sequencing the genome of their participants to elucidate the role of rare risk variation in the genetic architecture of complex phenotypes, including psychiatric traits. This dissertation sought to better understand the role of both common and rare risk variation in the genetic architecture of psychiatric disorders with a particular focus on schizophrenia and alcohol problems. In the first three analyses, we focused on characterizing …

Quantifying Contributions Of Climate, Geography, And Gene Flow To Divergence: A Case Study For Three North American Pines, Constance E. Bolte

Theses and Dissertations

Long-lived species of trees, especially conifers, often display weak patterns of reproductive isolation, but clear patterns of local adaptation and phenotypic divergence. Discovering the evolutionary history of these patterns is paramount to a generalized understanding of speciation and the processes that confer population persistence versus those that compromise adaptive potential under rapidly changing environments. Forest trees have long generation times and low migratory potential making them especially vulnerable to population fragmentation and reductions of genetic diversity due to insufficient tracking of niche optima and adaptational lags. Within clades of the genus Pinus, evolutionary histories appear to be riddled with hybridization …

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 …

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 …

Statistical Inference Of Adaptation At Multiple Genomic Scales Using Supervised Classification And A Hidden Markov Model, Lauren A. Sugden

Biology and Medicine Through Mathematics Conference

No abstract provided.

Transcriptomic Profiling Of Postmortem Prefrontal Cortex And Nucleus Accumbens From Chronic Alcohol Abusers., Eric S. Vornholt

Theses and Dissertations

Alcohol use disorder (AUD) is a debilitating psychiatric illness that develops from a combination of genetic and environmental factors. While it is well documented that AUD is heritable, the shift from recreational alcohol use to abuse/dependence is poorly understood. In this dissertation, using postmortem brain tissue from individuals with alcohol dependence (AD), we profiled the genome-wide expression of circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) to better understand the impact of gene expression on the development of AUD. To achieve this, we performed two independent studies that explore transcriptome differences between AD cases and controls. The first of …

Novel Strategies To Overcome Carboplatin Resistance In Triple Negative Breast Cancer Using Patient Derived Xenografts, Mohammad A. Al Zubi

Theses and Dissertations

Triple-negative breast cancer (TNBC) patients have a poor prognosis and rely on chemotherapeutic treatment as standard of care. Often, they develop chemotherapy resistance, which leaves them without more therapeutic options, like targeted therapy. New models have been developed to test targeted inhibitors in human tumors, and they are known as patient-derived xenografts (PDX). These tumors are obtained from patients, then established and maintained in mice where they areused for tumor studies. In this work, we characterized 14 PDXs for their primary tumor growth rate and investigated metastatic propensity using spontaneous and experiment metastasis models. We utilized RNA-sequencing to characterize contributions …

Interspecific Gene Flow Potentiates Adaptive Evolution In A Hybrid Zone Formed Between Pinus Strobiformis And Pinus Flexilis, Mitra Menon

Theses and Dissertations

Species range margins are often characterised by high degrees of habitat fragmentation resulting in low genetic diversity and higher gene flow from populations at the core of the species range. Interspecific gene flow from a closely related species with abutting range margins can increase standing genetic diversity and generate novel allelic combinations thereby alleviating limits to adaptive evolution in range margin populations. Hybridization driven interspecific gene flow has played a key role in the demographic history of several conifer due to their life history characteristics such as weak crossability barriers and long generation times. Nevertheless, demonstrating whether introgression is adaptive …

Role Of Clic4 And The Synaptic Transcriptome In The Behavioral And Molecular Neurobiology Of Ethanol, Rory M. Weston

Theses and Dissertations

Alcohol use disorder (AUD) is a prevalent neuropsychiatric disease with profound health, social, and economic consequences. With an estimated 50% heritability, identifying genes that engender risk and contribute to the underlying neurobiological mechanisms represents an important first step in developing effective treatments. Gene expression studies are an important source of candidate genes for studying AUD, providing windows into the molecular machinery engaged by the brain in response to ethanol. Published studies have identified chloride intracellular channel 4 (Clic4) as an ethanol-regulated gene in brain capable of modulating sensitivity to sedation in multiple species. The functions of Clic4 are …

The Pseudomonas Aeruginosa Interactome: Insights Into Srna-Mediated Regulatory Networks, Christine M. Van Duyn

Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative bacterium found in various environmental niches including soil, water, hospital environments, and within a broad range of hosts. It is well known for its metabolic versatility and intrinsic and acquired resistance to a variety of antimicrobial agents. Moreover, this bacterium has a remarkable ability to adapt and survive in suboptimal environments by altering its transcriptional profile in response to nutrient deprivation, changes in temperature and pH, osmotic stress, the presence of reactive oxygen species (ROS), and exposure to antibiotics and host defenses. P. aeruginosa colonizes individuals with compromised immune systems and severe burn injuries and …

The Functional Importance Of Methyl Cpg Binding Domain Proteins 2 And 3 In Regulating Fetal Hemoglobin Expression In Human Adult Erythroid Cells, Alexander Azzo

Theses and Dissertations

Humans undergo two developmental switches in the predominantly expressed β-like globin chain during embryogenesis and fetal development. The first switch from embryonic (ε) to fetal (γ) occurs around week 5 of embryonic development, while the second switch from fetal to adult (β) globin occurs shortly after birth. By adulthood, fetal hemoglobin represents only 1-2% of total hemoglobin in the blood. As sufficiently elevated levels of fetal hemoglobin are beneficial for improving clinical outcomes in sickle cell disease and β-thalassemia, the mechanisms that enforce silencing of fetal hemoglobin expression postnatally are of great clinical significance. The methyl-CpG binding domain protein MBD2 …

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 …

Testing For Cryptic Diversity And Inference Of Population Structure In The Cosmopolitan Hoplonemertean Emplectonema Gracile (Nemertea), Paul L. Delaney Iv

Theses and Dissertations

Emplectonema gracile (Johnston 1837) is a hoplonemertean of marine intertidal hard-bottom communities and is distributed throughout the Northern Hemisphere. Although possessing a planktonic larval stage in its life history, the range of such cosmopolitan marine invertebrate species is often explained by cryptic speciation and anthropogenic transport. The purpose of this study is to test for possible cryptic species using mtDNA markers (COI and 16S rDNA) and to investigate population structure in E. gracile over a portion of its geographic range using mtDNA markers and ddRADseq nuclear SNP data. The results of both phylogenetic- and tree-based species delimitation revealed that E. …

Latent Growth Model Approach To Characterize Maternal Prenatal Dna Methylation Trajectories, Dana Lapato

Theses and Dissertations

Background. DNA methylation (DNAm) is a removable chemical modification to the DNA sequence intimately associated with genomic stability, cellular identity, and gene expression. DNAm patterning reflects joint contributions from genetic, environmental, and behavioral factors. As such, differences in DNAm patterns may explain interindividual variability in risk liability for complex traits like major depression (MD). Hundreds of significant DNAm loci have been identified using cross-sectional association studies. This dissertation builds on that foundational work to explore novel statistical approaches for longitudinal DNAm analyses. Methods. Repeated measures of genome-wide DNAm and social and environmental determinants of health were collected up to six …

Natural And Anthropogenic Drivers Of Tree Evolutionary Dynamics, Brandon M. Lind

Theses and Dissertations

Species of trees inhabit diverse and heterogeneous environments, and often play important ecological roles in such communities. As a result of their vast ecological breadth, trees have become adapted to various environmental pressures. In this dissertation I examine various environmental factors that drive evolutionary dynamics in threePinusspecies in California and Nevada, USA. In chapter two, I assess the role of management influence of thinning, fire, and their interaction on fine-scale gene flow within fire-suppressed populations of Pinus lambertiana, a historically dominant and ecologically important member of mixed-conifer forests of the Sierra Nevada, California. Here, I find evidence …

Using Mathematical Models Of Biological Processes In Genome-Wide Association Studies Of Psychiatric Disorders, Amy Cochran

Biology and Medicine Through Mathematics Conference

No abstract provided.

Oncogenic Nelfe Enhances Myc-Induced Hepatocellular Carcinogenesis, Hien Dang, Atsushi Takai, Marshonna Forgues, Yosawat Pomyen, Haiwei Mou, Wen Xue, Debashish Ray, Kevn Ha, Quiad Morris, Timothy Hughes, Xin Wei Wang

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Investigation On Genetic Modifiers Of Age At Onset Of Major Depressive Disorder, Huseyin Gedik

Theses and Dissertations

Major Depressive Disorder (MDD) is a complex multifactorial disorder, which would lead to disability. Environmental and genetic factors are involved in MDD etiology. The aim of this project was to identify loci modifying age at onset (AAO) of MDD using survival models after adjusting for Childhood Sexual Abuse (CSA). To achieve this aim, a dataset was made available by the China Oxford and VCU Experimental Research on Genetic Epidemiology (CONVERGE) consortium. The study population had 5,220 controls and 5,282 cases with MDD. We performed two univariate association analyses using Cox Proportional Hazard (Cox PH) models. These two are Full Sample …

Power Analysis In Applied Linear Regression For Cell Type-Specific Differential Expression Detection, Edmund Glass

Theses and Dissertations

The goal of many human disease-oriented studies is to detect molecular mechanisms different between healthy controls and patients. Yet, commonly used gene expression measurements from any tissues suffer from variability of cell composition. This variability hinders the detection of differentially expressed genes and is often ignored. However, this variability may actually be advantageous, as heterogeneous gene expression measurements coupled with cell counts may provide deeper insights into the gene expression differences on the cell type-specific level. Published computational methods use linear regression to estimate cell type-specific differential expression. Yet, they do not consider many artifacts hidden in high-dimensional gene expression …

Genomic Comparisons And Genome Architecture Of Divergent Trypanosoma Species, Katie Bradwell

Theses and Dissertations

Virulent Trypanosoma cruzi, and the non-pathogenic Trypanosoma conorhini and Trypanosoma rangeli are protozoan parasites with divergent lifestyles. T. cruzi and T. rangeli are endemic to Latin America, whereas T. conorhini is tropicopolitan. Reduviid bug vectors spread these parasites to mammalian hosts, within which T. rangeli and T. conorhini replicate extracellularly, while T. cruzi has intracellular stages. Firstly, this work compares the genomes of these parasites to understand their differing phenotypes. Secondly, genome architecture of T. cruzi is examined to address the effect of a complex hybridization history, polycistronic transcription, and genome plasticity on this organism, and study its highly …

Investigating The Molecular Etiologies Of Sporadic Als (Sals) Using Rna-Sequencing, David G. Brohawn

Theses and Dissertations

ALS is an often lethal disease involving degeneration of motor neurons in the brain and spinal cord. Current treatments only extend life by several months, and novel therapies are needed. We combined RNA-Sequencing, systems biology analyses, and molecular biology assays to elucidate sporadic ALS group-specific differences in postmortem cervical spinal sections (7 sALS and 8 control samples) that may be relevant to disease pathology. >55 million 2X150 RNA-sequencing reads per sample were generated and processed.

In Chapter 2, we used bioinformatics tools to identify nuclear differentially expressed genes (DEGs) between our two groups. Further, we used Weighted Gene Co-Expression Network …

System Genetic Analysis Of Mechanisms Underlying Excessive Alcohol Consumption, Maren L. Smith

Theses and Dissertations

Increased alcohol consumption over time is one of the characteristic symptoms of Alcohol Use Disorder (AUD). The molecular mechanisms underlying this escalation in intake is still the subject of study. However, the mesocortical and mesolimbic dopamine pathways, and the extended amygdala, because of their involvement in reward and reinforcement are believed to play key roles in these behavioral changes. Multiple gene expression studies have shown that alcohol affects the expression of thousands of genes in the brain. The studies discussed in this document use the systems biology technique of co-expression network analysis to attempt to find

patterns within genome-wide expression …