Genetics and Genomics Commons^™

Genomic Epidemiology Of Staphylococcus Aureus Sequence-Type 72, Sachitaa Senthilkumar

Honors Undergraduate Theses

Staphylococcus aureus (S. aureus, SA) is a gram-positive bacterial colonizer and pathogen commonly carried on the skin and in the anterior nares of humans. SA colonization may lead to a variety of non-invasive (e.g., skin and soft tissue infections, SSTIs) and invasive (e.g., bacteremia and osteomyelitis) infections. The SA population is comprised of multiple lineages that can be delineated through multi-locus sequence typing (MLST), which compares nucleotide sequences within seven housekeeping genes. Strains belonging to an MLST share a common evolutionary history and phenotypic characteristics like antibiotic resistance or virulence. As a result, the epidemiology of lineages can be …

“Regression To The Mean”: The Confluence Of Eugenics And Statistics In The 19th And 20th Centuries, Emrys G. King

Pomona Senior Theses

The work of this thesis is twofold — first, qualitatively characterizing the confluence between the British eugenics and statistics movements in the late 19th and early 20th centuries, and second, quantitatively analyzing the effect of this foundation on pedagogical materials in the growing field of statistics between 1880 and 1970. Towards the first goal, the history of the method of least squares, state statistics, and positive and negative eugenics are outlined, followed by a close reading of the foundational texts authored by Francis Galton and Karl Pearson that introduced linear regression. Towards the latter goal, English-language statistics textbooks published between …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M. Kusminski, Terry D. Hinds Jr., Philipp E. Scherer

Markey Cancer Center Faculty Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

Urobilin Derived From Bilirubin Bioconversion Binds Albumin And May Interfere With Bilirubin Interacting With Albumin: Implications For Disease Pathology, Kevin I. Williams, Priyanka Suryadevara, Chang-Guo Zhan, Terry D. Hinds Jr., Zachary A. Kipp

Markey Cancer Center Faculty Publications

Background/Objectives: Bilirubin is a hydrophobic molecule that binds the carrier protein albumin for transport through systemic circulation. Bilirubin is cleared from the body through the liver and excreted into the intestines, where the microbiota modifies the chemical structure, forming urobilin, which can be reabsorbed into circulation by the hepatic portal vein. Urobilin has no known function. It is also unknown whether urobilin binds albumin for transport in circulation. We hypothesized that because of the likeness of their chemical structures, urobilin would also bind albumin like bilirubin does. Methods: First, we used in silico docking to predict if urobilin would bind …

Dissecting The Biophysical Mechanisms Of Oleate Hydratase Association With Membranes, William A. Lathram, Robert J. Neff, Ashley N. Zalla, James D. Brien, Vivekanandan Subramanian, Christopher D. Radka

Markey Cancer Center Faculty Publications

This study investigates the dynamics of oleate hydratase (OhyA), a bacterial flavoenzyme from Staphylococcus aureus, and its interactions with lipid membranes, focusing on the factors influencing membrane binding and oligomerization. OhyA catalyzes the hydration of unsaturated fatty acids, playing a key role in bacterial pathogenesis by neutralizing host antimicrobial fatty acids. OhyA binds the membrane bilayer to access membrane-embedded substrates for catalysis, and structural studies have revealed that OhyA forms oligomers on membrane surfaces, stabilized by both protein-protein and protein-lipid interactions. Using fluorescence correlation spectroscopy (FCS), we examined the effects of membrane curvature and lipid availability on OhyA binding to …

Pattern Integration And Differentiation: Dual Process Model Of Episodic Memory, Hallvard Røe Evensmoen, Lars M. Rimol, Henning Stople Rise, Tor Ivar Hansen, Hamed Nili, Anderson M. Winkler, Asta K. Håberg

Human Genetics Publications

The role of precise timing in episodic memory remains obscure. We showed 139 participants episodes consisting of objects, and tested subsequent memory for the precise timing and order of the objects and episodes. Temporal compression of the episode enhanced memory for relative but not absolute timing of the objects’ presentation and their order. Conversely, temporal expansion between neighboring episodes was associated with successful memory for episode order. fMRI in 36 participants revealed that temporal compression of the episode was associated with more similar activation patterns within episodes in several brain regions including the posterior hippocampus. However, the activation pattern in …

Enhancing Clinical Trial Matching In Molecular Diagnostics: Using Natural Language Processing And Clustering Approaches In Hematological Malignancies, Gillian Fanning

Theses and Dissertations

Clinical trial matching is a critical component of personalized medicine, particularly in the management of hematologic malignancies. At Virginia Commonwealth University (VCU) Health, the Molecular Diagnostics (MDX) Lab produces somatic variant reports and recommends clinical trials based on the presence of clinically significant mutations. However, the current manual trial recommendation process is time-intensive and lacks scalability.

This study introduces a computational framework to streamline and standardize clinical trial matching using natural language processing (NLP) and unsupervised clustering. Trial brief descriptions were analyzed to extract frequent terms, and trials were grouped based on term similarity using joint dimensionality reduction and clustering. …

Identification Of Benzothiophene-Derived Inhibitors Of Flaviviruses By Targeting Rna-Dependent Rna Polymerase, Leah Liu Wang, Shazeed-Ul Karim, Aidan Hand, Ryan Brunkhorst, Mackenna Petersen, Sarah Altam, Yi Liu, Luwen Zhang, Fengwei Bai, Shi-Hua Xiang

School of Biological Sciences: Faculty Publications

Flaviviruses such as Dengue, West Nile, and Zika viruses are mosquito-borne RNA viruses that can cause serious diseases in humans. To develop effective drugs for treating these viruses’ infections, we create a new approach for developing common or shared drugs that may work for several different viral species of flaviviruses. It is based on the conserved RNA-dependent RNA polymerase (RdRp), which is the key enzyme for viral replication. We built up a common structure of RdRps (POLcon) from their consensus sequence. A conserved Triple-D structural motif was identified at the active site of POLcon that has been used for virtual …

Cath-Ddg: Towards Robust Mutation Effect Prediction On Protein-Protein Interactions Out Of Cath Homologous Superfamily, Guanglei Yu, Xuehua Bi, Teng Ma, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Protein-protein interactions (PPIs) are fundamental aspects in understanding biological processes. Accurately predicting the effects of mutations on PPIs remains a critical requirement for drug design and disease mechanistic studies. Recently, deep learning models using protein 3D structures have become predominant for predicting mutation effects. However, significant challenges remain in practical applications, in part due to the considerable disparity in generalization capabilities between easy and hard mutations. Specifically, a hard mutation is defined as one with its maximum TM-score < 0.6 when compared to the training set. Additionally, compared to physics-based approaches, deep learning models may overestimate performance due to potential data leakage.

Results: We propose new training/test splits that mitigate data leakage according to the CATH homologous superfamily. Under the constraints of physical …

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

UROP 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 …

Determination Of Structural Factors Contributing To Protection Of Zinc Fingers In Estrogen Receptor Α Through Molecular Dynamic Simulations, Patricia B. Lutz, Wesley R. Coombs, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

The ERα transcription factor that induces tumor growth is a potential target for breast cancer treatment. Each monomer of the ERα DNA-binding domain (ERαDBD) homodimer has two conserved (Cys)₄-type zinc fingers, ZF1 (N-terminal) and ZF2 (C-terminal). Electrophilic agents release Zn²⁺ by oxidizing the coordinating Cys of the more labile ZF2 to inhibit dimerization and DNA binding. Microsecond-length molecular dynamics (MD) simulations show that greater flexibility of ZF2 in the ERαDBD monomer leaves its Cys more solvent accessible and less shielded from electrophilic attack by sulfur-centered hydrogen bonds than ZF1 which is buried in the protein. In the …

The Importance Of Solution Studies For The Structural Characterization Of The Enterovirus 5' Cloverleaf, Morgan G. Daniels, Meagan E. Werner, Xiaobing Zuo, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enteroviruses initiate genomic replication via a highly conserved mechanism that is controlled by an RNA platform, also known as the 5' cloverleaf (5'CL). Here, we present a biophysical analysis of the 5'CL conformation of three enterovirus serotypes under various ionic conditions, utilizing CD spectroscopy, size-exclusion chromatography, and small-angle X-ray scattering. In general, a tendency toward a smaller monomeric hydrodynamic radius in the presence of salts was observed, but the exact structural signature of each 5'CL varied depending upon the serotype. Rhinovirus B14 (RVB14) exhibited at least two monomeric conformations and a low propensity for dimerization, while poliovirus 1 (PV1) showed …

Influence Of Multi-Species Data On Gene-Disease Associations In Substance Use Disorder Using Random Walk With Restart Models, Erich J. Baker, Everest U. Castaneda, Sharon Moore, Jason A. Bubier, Stephen K. Grady, Michael A. Langston, Elissa J. Chessler

Funded Scholarship

A major challenge lies in discovering, emphasizing, and characterizing human gene-disease and gene-gene associations. The limitations of data on the role of human gene products in substance use disorder (SUD) makes it challenging to transition from genetic associations to actionable insights. The integration of data from multiple diverse sources, including information-dense studies in model organisms, has the potential to address this gap. We demonstrate a modified performance of the Random Walk with Restart algorithm when multi-species data is integrated in the heterogeneous network within the context of SUD. Additionally, our approach distinguishes among disparate pathways derived from the Kyoto Encyclopedia …

Electrochemical Strategies For Microrna Quantification Leveraging Amplification And Nanomaterials: A Review, Alexander Hunt, Gymama Slaughter

Center for Bioelectronics Publications

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression and have emerged as critical biomarkers in various diseases, including cancer. Their stability in bodily fluids and role as oncogenes or tumor suppressors make them attractive targets for non-invasive diagnostics. However, conventional detection methods, such as Northern blotting, RT-PCR, and microarrays, are limited by low sensitivity, lengthy protocols, and limited specificity. Electrochemical biosensors offer a promising alternative, providing high sensitivity, rapid response times, portability, and cost-effectiveness. These biosensors translate miRNA hybridization events into quantifiable electrochemical signals, often leveraging redox-active labels, mediators, or intercalators. Recent advancements in nanomaterials and signal amplification …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

The Effects Of Plx 3397 On Fentanyl Escalation In Male And Female Sprague-Dawley Rats, Jakob Shaykin

Theses and Dissertations--Psychology

Purpose: A hallmark characteristic of opioid use disorder (OUD) is a persons’ ‘loss of control’, which leads to the compulsion to seek and obtain opioids, resulting in increased consumption. This phenomenon is known as ‘escalation of drug intake’. Chronic opioid use causes microglial reactivity and subsequent release of proinflammatory cytokines leading to neuroinflammation, weakening one’s executive control over drug taking and ultimately leading to greater use. Previous research in our laboratory has explored heterogeneity of fentanyl intake in extended access (6-hr) sessions and identified distinct endophenotypes of fentanyl intake. Moreover, we have observed a positive correlation between Treml1 expression …

General Kernel Machine Methods For Multi-Omics Integration And Genome-Wide Association Testing With Related Individuals, Amarise Little, Ni Zhao, Anna Mikhaylova, Angela Zhang, Wodan Ling, Florian Thibord, Andrew D. Johnson, Laura M. Raffield, Joanne E. Curran, John Blangero

School of Medicine Publications

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.g. genotypes and gene expression levels) on a phenotype, particularly while accommodating routine issues, such as having related subjects' data in analyses. In this paper, we extend an existing composite kernel machine regression model to integrate two multi-omics data types, while accommodating for general correlation structures amongst outcomes. Due …

Heterogeneous Clustering Of Multiomics Data For Breast Cancer Subgroup Classification And Detection, Joseph Pateras, Musaddiq Lodi, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

The rapid growth of diverse -omics datasets has made multiomics data integration crucial in cancer research. This study adapts the expectation–maximization routine for the joint latent variable modeling of multiomics patient profiles. By combining this approach with traditional biological feature selection methods, this study optimizes latent distribution, enabling efficient patient clustering from well-studied cancer types with reduced computational expense. The proposed optimization subroutines enhance survival analysis and improve runtime performance. This article presents a framework for distinguishing cancer subtypes and identifying potential biomarkers for breast cancer. Key insights into individual subtype expression and function were obtained through differentially expressed gene …

Deepssetracer 2.0: Improved Deep Learning Model Performance For Protein Secondary Structure Segmentation From Cryo-Em Maps, Bryan Hawickhorst, Thu Nguyen, Willy Wriggers, Jiangwen Sun, Jing He

Computer Science Faculty Publications

DeepSSETracer is a method for segmenting protein secondary structure from medium-resolution (5-10Å) cryogenic electron microscopy (cryo-EM) density maps. We conducted experiments and ablation studies to examine the effects of normalization methods, max-pooling, activation functions, and loss calculation region on DeepSSETracer. By combining multiple technical improvements, the performance of the new version, DeepSSETracer 2.0, was significantly enhanced compared to DeepSSETracer 1.1. On a set of 77 test cases, the weighted average per-voxel F1 score increased from 62.1% to 70.3% for helix detection, and from 47.8% to 62.5% for β-sheet detection. While each of the five modifications in the network enhanced the …

Polygenic Risk Scores Of Grip Strength In Men And Women With Or At Risk For Hiv, Sreevidya Sadananda Sadasiva Rao

Electronic Theses & Dissertations (2024 - present)

Background: Adequate hand function among older adults is necessary for the successful completion of activities of daily living and can affect whether an older adult is able to live independently. Current research highlights grip strength, the strength people have in their hands, as a robust predictor of morbidity and mortality, and explores the decline in grip strength over time. A person’s family history and genes (DNA) affect how much grip strength they have. Previous studies have identified genes that affect grip strength, mainly in European ancestry populations. In this study, we examined whether these genetic elements predict grip strength in …

Codon Composition In Human Oocyters Reveals Age-Associated Defects In Mrna Decay, Pavla Brachova, Lane K. Christenson, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Oocytes from women of advanced reproductive age exhibit diminished developmental potential, but the underlying mechanisms remain incompletely defined. Oocyte maturation depends on translational control of maternal mRNA synthesized during growth. We performed a computational analysis on human oocytes from women < 30 versus ≥40 years and observed that mRNA GC content correlates negatively with half-life in oocytes from young (< 30 yr) but positively with oocytes from aged (>40 yr) women. In young oocytes, longer mRNA half-life is associated with lower protein abundance, whereas in aged oocytes GC content correlates positively with protein abundance. During the GV-to-MII transition, codon composition stratifies stability: codons that support rapid translation (optimal) stabilize mRNA, while slow-translating codons (non-optimal) promote decay. With reproductive aging, GC-containing codons become more optimal and align with increased …

Longitudinal Host Transcriptional Responses To Sars-Cov-2 Infection In Adults With Extremely High Viral Load, Vasanthi Avadhanula, Chad J Creighton, Laura Ferlic-Stark, Divya Nagaraj, Yiqun Zhang, Richard Sucgang, Erin G Nicholson, Anubama Rajan, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Ginger A Metcalf, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Richard A Gibbs, Joseph F Petrosino, Pedro A Piedra

Faculty, Staff and Students Publications

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2. We could identify widespread transcriptional host responses to SARS-CoV-2 infection that were initially most strongly manifested in patients with extremely high initial viral loads, then attenuating within the patient over time as viral loads decreased. Genes …

Goldenbraid20 E Coli: A Comprehensive And Characterized Toolkit For Enterics, Matthew B Cooke, Kobie T Welch, Laura D Ramirez, Alice X Wen, David C Marciano, Christophe Herman

Faculty, Staff and Students Publications

Modular cloning systems streamline laboratory workflows by consolidating genetic 'parts' into reusable and modular collections, enabling researchers to fast-track strain construction. The GoldenBraid 2.0 modular cloning system utilizes the cutting property of type IIS restriction enzymes to create defined genetic 'grammars', which facilitate the reuse of standardized genetic parts and assembly of genetic parts in the right order. Here, we present a GoldenBraid 2.0 toolkit of genetic parts designed to accelerate cloning in the model bacterium

Research For All: Building A Diverse Researcher Community For The All Of Us Research Program, Rubin Baskir, Minnkyong Lee, Sydney J Mcmaster, Jessica Lee, Faith Blackburne-Proctor, Romuladus Azuine, Nakia Mack, Sheri D Schully, Martin Mendoza, Janeth Sanchez, Yong Crosby, Erica Zumba, Michael Hahn, Naomi Aspaas, Ahmed Elmi, Shanté Alerté, Elizabeth Stewart, Danielle Wilfong, Meag Doherty, Margaret M Farrell, Grace B Hébert, Sula Hood, Cheryl M Thomas, Debra D Murray, Brendan Lee, Louisa A Stark, Megan A Lewis, Jen D Uhrig, Laura R Bartlett, Edgar Gil Rico, Adolph Falcón, Elizabeth Cohn, Mitchell R Lunn, Juno Obedin-Maliver, Linda Cottler, Milton Eder, Fornessa T Randal, Jason Karnes, Kitani Lemieux, Nelson Lemieux, Nelson Lemieux, Lilanta Bradley, Ronnie Tepp, Meredith Wilson, Monica Rodriguez, Chris Lunt, Karriem Watson

Faculty, Staff and Students Publications

OBJECTIVES: The NIH All of Us Research Program (All of Us) is engaging a diverse community of more than 10 000 registered researchers using a robust engagement ecosystem model. We describe strategies used to build an ecosystem that attracts and supports a diverse and inclusive researcher community to use the All of Us dataset and provide metrics on All of Us researcher usage growth.

MATERIALS AND METHODS: Researcher audiences and diversity categories were defined to guide a strategy. A researcher engagement strategy was codeveloped with program partners to support a researcher engagement ecosystem. An adapted ecological model guided the ecosystem …

What Are The Genetic Influences Of Alcohol Sensitivity And Alcohol Metabolism? A Narrative Review Of Human Studies, Erwin Murray, Karen G. Chartier Phd, Msw

UROP Posters

Background: Alcohol sensitivity and alcohol metabolism are two phenotypes associated with alcohol use disorder (AUD) influenced by genetics. This narrative review aims to answer “What are the genetic influences of alcohol sensitivity and alcohol metabolism?” to gain a better understanding of the genetic aspects of AUD.

Methods: A database search was performed in PubMed. Empirical human genetic studies published between 2009 and 2025 that focused on alcohol sensitivity (measured by the Self-Rating of the Effects of Alcohol scale) or alcohol-metabolizing genes were eligible for review. Studies were screened to determine inclusion for the current review.

Findings: Fifteen …

Zic1 Is A Context-Dependent Medulloblastoma Driver In The Rhombic Lip, John J Y Lee, Ran Tao, Zhen You, Parthiv Haldipur, Anders W Erickson, Hamza Farooq, Liam D Hendriske, Namal Abeysundara, Cory M Richman, Evan Y Wang, Neha Das Gupta, Jennifer Hadley, Melissa Batts, Christopher W Mount, Xiaochong Wu, Alex Rasnitsyn, Swneke Bailey, Florence M G Cavalli, Sorana Morrissy, Livia Garzia, Kulandaimanuvel Antony Michealraj, Abhi Visvanathan, Vernon Fong, Jonelle Palotta, Raul Suarez, Bryn G Livingston, Miao Liu, Betty Luu, Craig Daniels, James Loukides, Anne Bendel, Pim J French, Johan M Kros, Andrey Korshunov, Marcel Kool, Fernando Chico Ponce De León, Mario Perezpeña-Diazconti, Boleslaw Lach, Sheila K Singh, Sarah E S Leary, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji-Yeoun Lee, Teiji Tominaga, William A Weiss, Joanna J Phillips, Shizhong Dai, Gelareh Zadeh, Ali G Saad, László Bognár, Almos Klekner, Ian F Pollack, Ronald L Hamilton, Young-Shin Ra, Wieslawa A Grajkowska, Marta Perek-Polnik, Reid C Thompson, Anna M Kenney, Michael K Cooper, Stephen C Mack, Nada Jabado, Mathieu Lupien, Marco Gallo, Vijay Ramaswamy, Mario L Suva, Hiromichi Suzuki, Kathleen J Millen, L Frank Huang, Paul A Northcott, Michael D Taylor

Faculty, Staff and Students Publications

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma). Overexpression of ZIC1 suppresses the growth of group 3 medulloblastoma models, whereas it promotes the proliferation of SHH medulloblastoma precursor cells. SHH medulloblastoma ZIC1 mutants show increased activity versus wild-type ZIC1, whereas G4 medulloblastoma …

Copula-Based Bayesian Model For Detecting Differential Gene Expression, Prasansha Liyanaarachchi, N. Rao Chaganty

Mathematics & Statistics Faculty Publications

Deoxyribonucleic acid, more commonly known as DNA, is a fundamental genetic material in all living organisms, containing thousands of genes, but only a subset exhibit differential expression and play a crucial role in diseases. Microarray technology has revolutionized the study of gene expression, with two primary types available for expression analysis: spotted cDNA arrays and oligonucleotide arrays. This research focuses on the statistical analysis of data from spotted cDNA microarrays. Numerous models have been developed to identify differentially expressed genes based on the red and green fluorescence intensities measured using these arrays. We propose a novel approach using a Gaussian …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D' Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: von Hippel-Lindau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C …

Late Diagnosis Of Klinefelter Syndrome: Overcoming Phenotypic Variability And Diagnostic Oversights, Amna Kamran, Chinelo Okigbo

Department of Medicine Faculty Publications

We report a case of Klinefelter syndrome (KS) diagnosed in adulthood, emphasizing the impact of phenotypic variability and the declining reliance on physical examination in delayed recognition. A 27-year-old male with obesity, low libido, and biochemical and clinical primary hypogonadism was found to have 47, XXY karyotype, consistent with KS. His hypogonadism was initially attributed to obesity and overlooked, despite classic signs of a micropenis and small testes. The case highlights the importance of physical examination, comprehensive history, and clinician awareness in diagnosing KS, particularly in atypical presentations. KS is associated with increased risks of osteoporosis, cardiovascular disease, and psychosocial …

A Non-Toxic Analgesic Elicits Cell-Specific Genomic And Epigenomic Modulation By Targeting The Pag Brain Region, Hernan A. Bazan, Brian L. Giles, Surjyadipta Bhattacharjee, Scott Edwards, Nicolas G. Bazan

School of Medicine Faculty Publications

Acetaminophen (ApAP) is widely used for pain management, but overuse or overdose leads to hepatotoxicity, making it the leading cause of acute liver failure globally. There is an urgent need for safer pain medications, as other non-opioid analgesics like non-steroidal anti-inflammatory drugs (NSAIDs) are nephrotoxic. We have identified SRP-001 as a safer, non-hepatotoxic, novel analgesic that overcomes ApAP's limitations by avoiding NAPQI formation and preserving hepatic tight junctions. Using coupled RNA and ATAC sequencing, from the periaqueductal gray (PAG) midbrain region, we compared the genetic and epigenetic signatures of SRP-001 and ApAP treatments following complete Freund's adjuvant (CFA)-induced inflammatory pain …