Medical Molecular Biology Commons^™

Bayesian Covariate-Dependent Circadian Modeling Of Rest-Activity Rhythms, Beniamino Hadj-Amar, Vaishnav Krishnan, Marina Vannucci

Faculty, Staff and Students Publications

We propose a Bayesian covariate-dependent anti-logistic circadian model for analyzing activity data collected via wrist-worn wearable devices. The proposed approach integrates covariates into the modeling of the amplitude and phase parameters, facilitating cohort-level analysis with enhanced flexibility and interpretability. To promote model sparsity, we employ an l1-ball projection prior, enabling precise control over complexity while identifying significant predictors. We assess performances on simulated data and then apply the method to real-world actigraphy data from people with epilepsy. Our results demonstrate the model’s effectiveness in uncovering complex relationships among demographic, psychological, and medical factors influencing rest-activity rhythms, offering insights for …

Epilepsy Clinic Analytics: Leveraging Emr Reporting Tools To Characterize Center Volume And Complexity, Vanuli Arya, Arindam Ghosh Mazumder, Muna Nnamani, Mark A Abboud, Samuel C Lee, Michael S Guzman, Vaishnav Krishnan

Faculty, Staff and Students Publications

Introduction: Epilepsy centers connect patients to multidisciplinary provider groups that can coordinate surgical interventions and/or investigational treatments. Automated techniques to cross-sectionally review patient volume and complexity may reveal objective metrics to assign appropriate personnel and resources. Here, we leveraged an electronic medical record (EMR) reporting tool to examine how patient and visit volumes, antiseizure medication (ASM) prescriptions and neuromodulation use evolved over an 11-year epoch at a single level 4 adult epilepsy center in Texas, USA.

Methods: Using Epic Workbench Reporting, we acquired the dates of (i) all clinic visits (office or telemedicine), (ii) CPT codes for neuromodulation interrogation/programming, and …

Id-Gba: Subgraph Extension With Information Distance Guilt By Association In Complex Networks, Predrag Obradovic, Vladimir Kovacevic, Aleksandar Milosavljevic, Varduhi Petrosyan

Faculty, Staff and Students Publications

Here, we introduce the ID-GBA (Information Distance Guilt By Association) method to expand highly connected sets of nodes by deploying a novel algorithm for subgraph extension based on the guilt-by-association principle and information distance. In this study, ID-GBA was utilized to expand disease clusters, and identify novel disease genes. We first validate its ability to expand related disease sets from disease/disease graphs built using Open Targets' gene association scores. We then analyze disease/control gene expression networks and show that ID-GBA recaptures known disease genes in nine disease/control graphs. Compared to existing methods such as Random Walk with Restarts and Personalized …

Heterologous Prime-Pull Mucosal Vaccination With An Adjuvanted Rbd Vaccine Elicits Robust Iga Production And Protects Against Sars-Cov-2, Allyson H Hirsch, Calder R Ellsworth, William A Lewis, Ryan Craig, Amy E Meyer, Jonatan Maldonado, Frania Ramirez Lopez, Syamala Rani Thimmiraju, James B Mclachlan, Xuebin Qin, Nicholas J Maness, Jeroen Pollet, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Lisa A Morici

Faculty, Staff and Students Publications

Despite the efficacy of approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in preventing severe disease and death, breakthrough infections continue to occur in vaccinated individuals, contributing to further viral mutation and spread. These limitations may be attributable to the poor induction of mucosal immunity by parenteral vaccination. Mucosal adjuvants, such as T-vant, can enhance vaccine-induced immune responses through the generation of antigen-specific antibodies and T cells in the respiratory tract. In this study, we evaluated the protective efficacy of adjuvanted SARS-CoV-2 receptor binding domain (RBD) subunit vaccines administered by homologous and heterologous routes. Immunized mice were challenged with …

The Dna Demethylase Tet1 Modifies The Impact Of Maternal Folic Acid Status On Embryonic Brain Development, Lehua Chen, Bernard K Van Der Veer, Qiuying Chen, Spyridon Champeris Tsaniras, Wannes Brangers, Harm H M Kwak, Rita Khoueiry, Yunping Lei, Robert Cabrera, Steven S Gross, Richard H Finnell, Kian Peng Koh

Faculty, Staff and Students Publications

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1−/− embryos and are resistant to FA supplementation across strains. Maternal diets that are either too rich or deficient in FA are linked to an increased incidence of cranial deformities in wild type and Tet1+/− offspring and to …

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 …

Gut Microbial Community Structure Of The Adult Citrus Root Weevil Diaprepes Abbreviatus, Imilce A Rodriguez-Fernandez, Tasha M Santiago-Rodriguez, Paola G Figueroa-Pratts, Keislamarí Cintrón-Berríos, Nichole D Rodriguez-Cornier, Gary A Toranzos

Faculty, Staff and Students Publications

Diaprepes abbreviatus is an agricultural pest known to affect around 270 plant species across the Caribbean and the United States, posing significant challenges to pest management. Chemical control dominates management, but environmental and health concerns motivate microbiome-informed alternatives. However, limited information exists on the gut anatomy, physicochemical environment, and microbial composition of D. abbreviatus. In this study, we provide the first comprehensive characterization of the gut morphology, pH, and microbiota of adult D. abbreviatus in both females and males collected in Puerto Rico. Using dye-based gut tracing, we identified foregut, midgut, and hindgut or posterior gut compartments, and confirmed the …

Transposable Element Activity Captures Human Pluripotent Cell States, Florencia Levin-Ferreyra, Srikanth Kodali, Yingzhi Cui, Alison R S Pashos, Patrizia Pessina, Justin Brumbaugh, Bruno Di Stefano

Faculty, Staff and Students Publications

Human pluripotent stem cells (hPSCs) exist in multiple, transcriptionally distinct states and serve as powerful models for studying human development. Despite their significance, the molecular determinants and pathways governing these pluripotent states remain incompletely understood. Here, we demonstrate that transposable elements act as sensitive indicators of distinct pluripotent cell states. We engineered hPSCs with fluorescent reporters to capture the temporal expression dynamics of two state-specific transposable elements, LTR5_Hs, and MER51B. This dual reporter system enables real-time monitoring and isolation of stem cells transitioning from naïve to primed pluripotency and further towards differentiation, serving as a more accurate readout of pluripotency …

Age-Related Variations In Hba1c Improvemecnts: Insights From A Telehealth-Supported Community-Based Intervention, Laura Porterfield, Xiaoying Yu, Amber B Amspoker, Craig A Johnston, Aanand D Naik, Salim S Virani, Christie M Ballantyne, Ashok Balasubramanyam, Elizabeth M Vaughan

Faculty, Staff and Students Publications

Background and objectives: We previously demonstrated that a telehealth-supported community health worker (CHW) intervention significantly improved clinical outcomes in diabetes care. However, the extent to which these benefits vary across different age groups remains unclear. This study evaluated the effectiveness of a CHW-led multidimensional diabetes intervention in reducing HbA1c across age groups.

Research design and methods: We conducted a retrospective analysis of 10 studies (n = 301) that focused on low-income Hispanic adults with or at risk for type 2 diabetes. The intervention included CHW-participant coaching via mobile Health (mHealth), monthly CHW-led group education, and bidirectional mHealth feedback among …

Reliable Rna-Seq Analysis From Ffpe Specimens As A Means To Accelerate Cancer-Related Health Disparities Research, Mitchell J Frederick, Dannelys Perez-Bello, Pedram Yadollahi, Patricia Castro, Alan Frederick, Andrew Frederick, Rashid A Osman, Fonma Essien, Imelda Yebra, Ashley Hamlin, Thomas J Ow, Heath D Skinner, Vlad C Sandulache

Faculty, Staff and Students Publications

Whole transcriptome sequencing (WTS/ RNA-Seq) is a ubiquitous tool for investigating cancer biology. RNA isolated from frozen sources limits possible studies for analysis of associations with phenotypes or clinical variables requiring long-term follow-up. Although good correlations are reported in RNA-Seq data from paired frozen and formalin fixed paraffin embedded (FFPE) samples, uncertainties regarding RNA quality, methods of extraction, and data reliability are hurdles to utilization of archival samples. We compared three different platforms for performing RNA-seq using archival FFPE oropharyngeal squamous carcinoma (OPSCC) specimens stored up to 20 years, as part of an investigation of transcriptional profiles related to health …

Inhibition Of Ribosome Biogenesis In Vivo Causes P53-Dependent Death And P53-Independent Dysfunction, Charles J Cho, Thanh Nguyen, Amala K Rougeau, Yang-Zhe Huang, Sarah To, Xiaobo Lin, Supuni Thalalla Gamage, Jordan L Meier, Jason C Mills

Faculty, Staff and Students Publications

Background & aims: Although it is well-known that ribosomes are critical for cell function, and their synthesis (known as ribosome biogenesis [RiBi]) is energy-intensive, surprisingly little is known about RiBi in vivo in adult tissue.

Methods: Using a mouse model with conditional deletion of Nat10, an essential gene for RiBi and subsequent translation of mRNA, we investigated the effects of RiBi blockade in vivo, with a focus on pancreatic acinar cells during homeostasis and tumorigenesis.

Results: We observed an unexpected latency of several weeks between Nat10 deletion and onset of structural and functional abnormalities and p53-dependent acinar cell death. Although …

Relationships Of Personality Traits With The Taxonomic Composition Of The Gut Microbiome Among Psychiatric Inpatients, William Orme, Sandra L Grimm, Divya S N Vella, J Christopher Fowler, B Christopher Frueh, Benjamin L Weinstein, Joseph Petrosino, Cristian Coarfa, Alok Madan

Faculty, Staff and Students Publications

Objective: Through the brain-gut-microbiome axis, myriad psychological functions that affect behavior share a dynamic, bidirectional relationship with the intestinal microbiome. Little is known about the relationship between personality-a stable construct that influences social- and health-related behaviors-and the bacterial ecosystem. The authors of this exploratory study examined the relationship between general and maladaptive personality traits and the composition of the gut microbiome.

Methods: In total, 105 psychiatric inpatients provided clinical data and fecal samples. Personality traits were measured with the five-factor model of personality, the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and the Personality Inventory for DSM-5; 16S …

Experiences From Dual Genome Next-Generation Sequencing Panel Testing For Mitochondrial Disorders: A Comprehensive Molecular Diagnosis, Elizabeth Gorman, Hongzheng Dai, Yanming Feng, William James Craigen, David C Y Chen, Fan Xia, Linyan Meng, Pengfei Liu, Robert Rigobello, Arpita Neogi, Christine M Eng, Yue Wang

Faculty, Staff and Students Publications

Introduction: The molecular diagnosis of mitochondrial disorders is complicated by phenotypic variability, genetic heterogeneity, and the complexity of mitochondrial heteroplasmy. Next-generation sequencing (NGS) of the mitochondrial genome in combination with a targeted panel of nuclear genes associated with mitochondrial disease provides the highest likelihood of obtaining a comprehensive molecular diagnosis. To assess the clinical utility of this approach, we describe the results from a retrospective review of patients having dual genome panel testing for mitochondrial disease.

Methods: Dual genome panel testing by NGS was performed on a cohort of 1,509 unrelated affected individuals with suspected mitochondrial disorders. This test included …

Paternal Upd (15) With Disease-Causing Mutation And Small Supernumerary Ring Chromosome 15: A Case Report, David Lee Curtis, Nasim Bekheirnia, Lorraine Potocki, Ludmila Matyakhina, Mir Reza Bekheirnia

Faculty, Staff and Students Publications

Uniparental disomy (UPD) constitutes an unconventional mode of inheritance that disrupts the typical biparental genetic contribution and may result in phenotypic abnormalities. This report centers on a patient diagnosed with Bartter syndrome Type 1, attributed to a homozygous pathogenic variant in SLC12A1 unmasked by mosaic paternal UPD of chromosome 15. We hypothesize that this pattern (or constellation) emerged from a trisomy rescue event, resulting in two distinct cell lines. Concurrently, the unmasking of a pathogenic paternal SLC12A1 variant by trisomy rescue resulted in the manifestation of Bartter syndrome Type 1. The maternally derived ring chromosome 15 and its impact on …

Autosomal Dominant Hk1-Related Neurodevelopmental Disorder With Visual Defects And Brain Anomalies (Nedviba): An Emerging Mitochondrial Disorder, Bobby G Ng, Erik A Eklund, Jill A Rosenfeld, Abdallah F Elias, Aya Abu-El-Haija, Celine Bris, Magalie Barth, Jong-Hee Chae, Murim Choi, Holly A Dubbs, Carl Fratter, Nicola Foulds, Candace Gamble, Ralitza H Gavrilova, Jaclyn Haven, Trevor L Hoffman, Jill V Hunter, Austin Larson, Timothy Edward Lotze, Pilar Magoulas, Emily C Magness, Debra M Bootin, Eric D Marsh, Victoria Nesbitt, Matthew T Pastore, Joanna Poulton, Shamima Rahman, Fernando Scaglia, Chaya Murali, Jennifer Posey, Joshua Rotenberg, Betsy Schmalz, Deepali N Shinde, Zöe Powis, Rivka Sukenik-Halevy, Kristen V Truxal, Tami Uster, Matheus Vernet Machado Bressan Wilke, Erik Klee, Hyewon Woo, Donald Younkin, Jianhua Zhao, Jorge Granadillo, Seema Lalani, David Chitayat, Wendy K Chung, Hudson H Freeze, Volkan Okur

Faculty, Staff and Students Publications

Purpose: Hexokinase 1 (HK1) encodes a ubiquitously expressed hexokinase, which is responsible for the first step of glycolysis, phosphorylation of glucose to glucose-6-phosphate. Both autosomal recessive and dominant variants in this gene have previously been shown to cause human disease, and presently, there are clinical data available for 27 individuals with the monoallelic neurodevelopmental disorder with visual defects and brain anomalies. Delineation of the entire phenotypic spectrum and genotype-phenotype relations will aid in management and counseling decisions.

Methods: We present molecular and clinical data on 22 additional individuals with heterozygous, mostly de novo, variants in HK1. We …

Monoallelic Expression Can Govern Penetrance Of Inborn Errors Of Immunity, O'Jay Stewart, Conor Gruber, Haley E Randolph, Roosheel Patel, Meredith Ramba, Enrica Calzoni, Lei Haley Huang, Jay Levy, Sofija Buta, Angelica Lee, Christos Sazeides, Zoe Prue, David P Hoytema Van Konijnenburg, Ivan K Chinn, Luis A Pedroza, James R Lupski, Erica G Schmitt, Megan A Cooper, Anne Puel, Xiao Peng, Stéphanie Boisson-Dupuis, Jacinta Bustamante, Satoshi Okada, Marta Martin-Fernandez, Jordan S Orange, Jean-Laurent Casanova, Joshua D Milner, Dusan Bogunovic

Faculty, Staff and Students Publications

Inborn errors of immunity (IEIs) are genetic disorders that underlie susceptibility to infection, autoimmunity, autoinflammation, allergy and/or malignancy1. Incomplete penetrance is common among IEIs despite their monogenic basis2. Here we investigate the contribution of autosomal random monoallelic expression (aRMAE), a somatic commitment to the expression of one allele3,4, to phenotypic variability observed in families with IEIs. Using a clonal primary T cell system to assess aRMAE status of genes in healthy individuals, we find that 4.30% of IEI genes and 5.20% of all genes undergo aRMAE. Perturbing H3K27me3 and DNA methylation alters …

Correction: Genetic Landscape Of Hypertrophic Cardiomyopathy In Hong Kong Chinese Population, Derek P H Lee, Ye Cao, Lilei Zhang

Faculty, Staff and Students Publications

[This corrects the article DOI: 10.3389/fgene.2025.1583838.].

Examining Parents’ Perceptions Of Their Children’S Autism And Completion Of Genetic Testing, Georgina J Sakyi, Sarah S Mire, Robin P Goin-Kochel, Chaya N Murali, Susan X Day

Faculty, Staff and Students Publications

Though genetic testing is recommended for children diagnosed with autism spectrum disorder (ASD), both internal (e.g. parents’ and providers’ valuation of genetic testing) and external (e.g. insurance coverage) barriers exist, and exploration of these factors is required to close the gap between provider recommendations and parent follow-through. In a sample of 290 parents, we explored (a) how parents’ ASD-related etiological beliefs and symptom attributions, as well as income, affected genetic testing completion; and (b) whether these factors influence parents’ hopes or concerns about genetic testing. Principal component analysis (PCA) was used to investigate the factor structure of the ASD attribution …

Whole Exome Sequencing As A Screening Tool In Dogs: A Pilot Study, Fréderique Boeykens, Evelien Bogaerts, Liesbeth Vossaert, Luc Peelman, Filip Van Nieuwerburgh, Jimmy H Saunders, Bart J G Broeckx

Faculty, Staff and Students Publications

Background: Whole-exome sequencing (WES) is used to selectively sequence all exons of protein-coding genes. WES is considered as a cost-effective and direct approach for identifying phenotype-associated variants in protein-coding regions and is as such situated between the traditional Sanger sequencing and whole genome sequencing (WGS). While WES is already widely used as a clinical tool in human and medical genetics, its use in veterinary medicine is currently restricted to research purposes. In this article, we aimed to provide baseline performance characteristics of a WES design to assess its suitability with future applications in veterinary clinical genetics in mind.

Methods: To …

Mixed-Methods Evaluation And Behavior Change Interventions To Improve Hand Hygiene Resources And Practices Among Healthcare Workers In Polyclinics And Health Centers In Belize, 2023, Anh N Ly, Kelsey Mcdavid, Christina Craig, Rosalva Blanco, Vickie Romero, Melissa Diaz-Musa, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Makenzie Towery, Anna Impellitteri, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Background: Hand hygiene (HH) is an effective public health measure to prevent the spread of infections in healthcare settings. A previous study in Belize showed gaps in HH practices in hospitals and large polyclinics; however, there are limited national data assessing access to and use of HH resources in smaller outpatient primary care facilities, especially in rural areas.

Methods: In February 2023, facility assessments were conducted at 26 health centers and polyclinics in Belize to assess the availability of HH resources. Of these, 12 pilot healthcare facilities (HCF) were selected for additional evaluation, which included observation of HH practices, hand …