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Old Dominion University

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Articles 31 - 60 of 273

Full-Text Articles in Genetics and Genomics

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 Jan 2025

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 …


A Survey On Deep Learning For Drug-Target Binding Prediction: Models, Benchmarks, Evaluation, And Case Studies, Kusal Debnath, Pratip Rana, Preetam Ghosh Jan 2025

A Survey On Deep Learning For Drug-Target Binding Prediction: Models, Benchmarks, Evaluation, And Case Studies, Kusal Debnath, Pratip Rana, Preetam Ghosh

Computer Science Faculty Publications

Conventional drug discovery is expensive, time-consuming, and prone to failure. Artificial intelligence has become a potent substitute over the last decade, providing strong answers to challenging biological issues in this field. Among these difficulties, drug-target binding (DTB) is a key component of drug discovery techniques. In this context, drug-target affinity and drug–target interaction are complementary and essential frameworks that work together to improve our comprehension of DTB dynamics. In this work, we thoroughly analyze the most recent deep learning models, popular benchmark datasets, and assessment metrics for DTB prediction. We look at the paradigm shift in the development of drug …


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 Jan 2025

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 Jan 2025

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 …


Electrochemical Strategies For Microrna Quantification Leveraging Amplification And Nanomaterials: A Review, Alexander Hunt, Gymama Slaughter Jan 2025

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 …


Anthropocene Genetic Diversity Loss In The Marine Tropics, René D. Clark, Brendan N. Reid, Eric Garcia, Marial Malabag, Robin S. Waples, Rene A. Abesamis, Jemelyn Grace P. Baldisimo, Abner A. Bucol, Kyra S. Fitz, Sharon F. Magnuson, Richard N. Muallil, Cleto L. Nanola Jr., Roy Roberts, John C. Whalen, Christopher E. Bird, Kent E. Carpenter, Malin L. Pinsky Jan 2025

Anthropocene Genetic Diversity Loss In The Marine Tropics, René D. Clark, Brendan N. Reid, Eric Garcia, Marial Malabag, Robin S. Waples, Rene A. Abesamis, Jemelyn Grace P. Baldisimo, Abner A. Bucol, Kyra S. Fitz, Sharon F. Magnuson, Richard N. Muallil, Cleto L. Nanola Jr., Roy Roberts, John C. Whalen, Christopher E. Bird, Kent E. Carpenter, Malin L. Pinsky

Biological Sciences Faculty Publications

Genetic diversity is a crucial component of biodiversity, and as such, its maintenance and preservation is of high conservation concern. Tropical environments are undergoing intense rates of environmental change, and these changes may be driving large declines in genetic diversity. However, data on genetic diversity are highly skewed towards temperate regions. The degree to which diversity loss has occurred in tropical species, particularly marine species, remains an open and important question. Here, we directly compare genomic data from modern and museum collections of two commercially-harvested nearshore marine fishes (Equulites laterofenestra and Gazza minuta) gathered from a single location …


Preservation Of Genetic Diversity And Selection Over A Century In A Coral Reef Fish (Taeniamia Zosterophora) In The Philippines, Kyra S. Fitz, Rene A. Abesamis, Jemelyn Grace P. Baldisimo, Abner A. Bucol, René D. Clark, Eric Garcia, Ivan R. Lopez, Sharon F. Magnuson, Marial J. Malabag, Richard N. Muallil, Lynne R. Parenti, Brendan R. Reid, Mudjekeewis D. Santos, Christopher E. Bird, Kent E. Carpenter, Malin L. Pinsky Jan 2025

Preservation Of Genetic Diversity And Selection Over A Century In A Coral Reef Fish (Taeniamia Zosterophora) In The Philippines, Kyra S. Fitz, Rene A. Abesamis, Jemelyn Grace P. Baldisimo, Abner A. Bucol, René D. Clark, Eric Garcia, Ivan R. Lopez, Sharon F. Magnuson, Marial J. Malabag, Richard N. Muallil, Lynne R. Parenti, Brendan R. Reid, Mudjekeewis D. Santos, Christopher E. Bird, Kent E. Carpenter, Malin L. Pinsky

Biological Sciences Faculty Publications

Evaluating the evolutionary impacts of anthropogenic activity on populations is key to understanding species resiliency and to designing effective conservation strategies. Sequencing DNA from historical specimens provides the opportunity to establish a historical baseline and empirically assess changes in genetic diversity, changes in effective population size, and selection over time. Here, we sequenced historical and contemporary samples of the cardinalfish Taeniamia zosterophora collected in 1908 and in 2021-2022 across two sites with differing human impact in the Philippines. At both sites, genetic diversity increased over time, with contemporary samples having significantly higher Watterson's Θ than historical samples. This diversity increase …


Symbiodiniaceae Shifts Over The Last Decade On The Hottest Coral Reefs On Earth, Anna Fiesinger, Rachel Alderdice, Luigi Colin, Hannah Manns, Gabriela Perna, Kathryn H. Stankiewicz, Jacob J. Valenzuela, Line K. Bay, Daniel J. Barshis, Nitin S. Baliga, Iliana B. Baums, John A. Burt, Christian R. Voolstra Jan 2025

Symbiodiniaceae Shifts Over The Last Decade On The Hottest Coral Reefs On Earth, Anna Fiesinger, Rachel Alderdice, Luigi Colin, Hannah Manns, Gabriela Perna, Kathryn H. Stankiewicz, Jacob J. Valenzuela, Line K. Bay, Daniel J. Barshis, Nitin S. Baliga, Iliana B. Baums, John A. Burt, Christian R. Voolstra

Biological Sciences Faculty Publications

Corals in the Persian/Arabian Gulf (PAG) are resilient to various stressors, whose levels exceed those of coral reefs globally. These corals thereby offer insight into mechanisms underlying thermal resilience, e.g., regarding the role of endosymbiotic microalgae in the family Symbiodiniaceae. Previous studies have identified the thermotolerant species Cladocopium thermophilum as broadly associated with corals in the southern PAG. However, algal-host specificity at the within-species level and the temporal stability of these associations are not well understood. Here we sampled two dominant stony corals (Porites harrisoni, n = 119 and Platygyra daedalea, n = 79) at three sites …


Heterogeneous Clustering Of Multiomics Data For Breast Cancer Subgroup Classification And Detection, Joseph Pateras, Musaddiq Lodi, Pratip Rana, Preetam Ghosh Jan 2025

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 Jan 2025

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 …


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 Jan 2025

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 Jan 2025

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 …


Codon Composition In Human Oocyters Reveals Age-Associated Defects In Mrna Decay, Pavla Brachova, Lane K. Christenson, Nehemiah S. Alvarez Jan 2025

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 …


Exploration Of Potential Broad-Spectrum Antiviral Targets In The Enterovirus Replication Element: Identification Of Six Distinct 5' Cloverleaves, Morgan G. Daniels, Meagan E. Werner, Rockwell T. Li, Steven M. Pascal Jan 2024

Exploration Of Potential Broad-Spectrum Antiviral Targets In The Enterovirus Replication Element: Identification Of Six Distinct 5' Cloverleaves, Morgan G. Daniels, Meagan E. Werner, Rockwell T. Li, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human health-related serotypes from the enterovirus genus, including enterovirus and rhinovirus species. Phylogenetic analysis indicates six distinct 5′CL serotypes that only partially correlate with the species definition. Additional findings include that 5′CL sequence conservation is higher between the EV species than between the RV species, the 5′CL of EVA and EVB are nearly identical, and RVC has the …


Electrophysiological And Clinical Fundamentals Of Qtc Prolongation Induced By Antipsychotic Medications, Zaid Naseer, Minaal Khan, Najeeb Manalai, Allison Foroobar, Patricia Harrison, Charles Scercy, Beth Yanoff, Partam Manalai Jan 2024

Electrophysiological And Clinical Fundamentals Of Qtc Prolongation Induced By Antipsychotic Medications, Zaid Naseer, Minaal Khan, Najeeb Manalai, Allison Foroobar, Patricia Harrison, Charles Scercy, Beth Yanoff, Partam Manalai

Department Surgery Faculty Publications

Patients with psychiatric disorders undergoing antipsychotic treatment are at an elevated risk for adverse cardiovascular events, including arrhythmias and sudden cardiac death. While the precise mechanisms linking cardiovascular diseases and psychiatric conditions remain unclear, QTc prolongation is suspected to be a contributing factor. The human ether-à-go-go-related gene (hERG, or KCNH2), which affects potassium channels, is implicated in the cardiotoxicity of various medications, including antipsychotics. This gene plays a critical role in determining whether a drug will be approved for market use. This paper elucidates the electrophysiological basis of QTc prolongation and reviews the evidence concerning which antipsychotics may exacerbate QTc …


Integrative Machine Learning Approaches For Enhanced Classification Of Genomic Sequences: A Next-Generation Sequencing Perspective, Sujatha Alla, Nagesh Bheesetty, Sai Gireesh Komaragiri, Prasanthi Chidipudi, Joshit Mohanty, Sathish Kumar Chintala, Jubin Thomas, Jayapal Vummadi, Hemanth Volikatla, Navin Kamuni Jan 2024

Integrative Machine Learning Approaches For Enhanced Classification Of Genomic Sequences: A Next-Generation Sequencing Perspective, Sujatha Alla, Nagesh Bheesetty, Sai Gireesh Komaragiri, Prasanthi Chidipudi, Joshit Mohanty, Sathish Kumar Chintala, Jubin Thomas, Jayapal Vummadi, Hemanth Volikatla, Navin Kamuni

Engineering Management & Systems Engineering Faculty Publications

The advent of Next-Generation Sequencing (NGS) techniques has revolutionized genomic research by enabling the rapid sequencing of DNA and RNA. This data can be used for various applications, including genome sequencing, transcriptome profiling, metagenomics, and epigenetics studies. For this study, DNA classifier dataset was extracted from UCI repository of machine learning databases. This vast amount of genomic data necessitates the development of sophisticated machine learning (ML) models for effective classification and analysis. This study presents a comprehensive comparison of various ML models, including Support Vector Machines (SVM), Random Forests (RF), and Neural Networks (NNs), approaches, in classifying genomic data. We …


Identifying New Cancer Genes Based On The Integration Of Annotated Gene Sets Via Hypergraph Neural Networks, Chao Deng, Hong-Dong Li, Li-Shen Zhang, Yiwei Liu, Yaohang Li, Jianxin Wang Jan 2024

Identifying New Cancer Genes Based On The Integration Of Annotated Gene Sets Via Hypergraph Neural Networks, Chao Deng, Hong-Dong Li, Li-Shen Zhang, Yiwei Liu, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation

Identifying cancer genes remains a significant challenge in cancer genomics research. Annotated gene sets encode functional associations among multiple genes, and cancer genes have been shown to cluster in hallmark signaling pathways and biological processes. The knowledge of annotated gene sets is critical for discovering cancer genes but remains to be fully exploited.

Results

Here, we present the DIsease-Specific Hypergraph neural network (DISHyper), a hypergraph-based computational method that integrates the knowledge from multiple types of annotated gene sets to predict cancer genes. First, our benchmark results demonstrate that DISHyper outperforms the existing state-of-the-art methods and highlight the advantages of …


Refining The Scope Of Genetic Influences On Alcohol Misuse Through Environmental Stratification And Gene-Environment Interaction, Jeanne E. Savage, Christiaan A. De Leeuw, Josefin Werme, Spit For Science Working Group, Danielle M. Dick, Danielle Posthuma, Sophie Van Der Sluis Jan 2024

Refining The Scope Of Genetic Influences On Alcohol Misuse Through Environmental Stratification And Gene-Environment Interaction, Jeanne E. Savage, Christiaan A. De Leeuw, Josefin Werme, Spit For Science Working Group, Danielle M. Dick, Danielle Posthuma, Sophie Van Der Sluis

Psychology Faculty Publications

Background

Gene-environment interaction (G X E) is likely an important influence shaping individual differences in alcohol misuse (AM), yet it has not been extensively studied in molecular genetic research. In this study, we use a series of genome-wide gene-environment interaction (GWEIS) and in silico annotation methods with the aim of improving gene identification and biological understanding of AM.

Methods

We carried out GWEIS for four AM phenotypes in the large UK Biobank sample (N = 360,314), with trauma exposure and socioeconomic status (SES) as moderators of the genetic effects. Exploratory analyses compared stratified genome-wide association (GWAS) and GWEIS modeling approaches. …


Ai And Ml-Based Risk Assessment Of Chemicals: Predicting Carcinogenic Risk From Chemical-Induced Genomic Instability, Ajay Vikram Singh, Preeti Bhardwaj, Peter Laux, Prachi Pradeep, Madleen Busse, Andreas Luch, Akihiko Hirose, Christopher J. Osgood, Michael W. Stacey Jan 2024

Ai And Ml-Based Risk Assessment Of Chemicals: Predicting Carcinogenic Risk From Chemical-Induced Genomic Instability, Ajay Vikram Singh, Preeti Bhardwaj, Peter Laux, Prachi Pradeep, Madleen Busse, Andreas Luch, Akihiko Hirose, Christopher J. Osgood, Michael W. Stacey

Biological Sciences Faculty Publications

Chemical risk assessment plays a pivotal role in safeguarding public health and environmental safety by evaluating the potential hazards and risks associated with chemical exposures. In recent years, the convergence of artificial intelligence (AI), machine learning (ML), and omics technologies has revolutionized the field of chemical risk assessment, offering new insights into toxicity mechanisms, predictive modeling, and risk management strategies. This perspective review explores the synergistic potential of AI/ML and omics in deciphering clastogen-induced genomic instability for carcinogenic risk prediction. We provide an overview of key findings, challenges, and opportunities in integrating AI/ML and omics technologies for chemical risk assessment, …


Hite: A Fast And Accurate Dynamic Boundary Adjustment Approach For Full-Length Transposable Element Detection And Annotation, Kang Hu, Peng Ning, Minghua Xu, You Zou, Jianye Chang, Xin Gao, Yaohang Li, Jue Ruan, Bin Hu, Jianxin Wang Jan 2024

Hite: A Fast And Accurate Dynamic Boundary Adjustment Approach For Full-Length Transposable Element Detection And Annotation, Kang Hu, Peng Ning, Minghua Xu, You Zou, Jianye Chang, Xin Gao, Yaohang Li, Jue Ruan, Bin Hu, Jianxin Wang

Computer Science Faculty Publications

Recent advancements in genome assembly have greatly improved the prospects for comprehensive annotation of Transposable Elements (TEs). However, existing methods for TE annotation using genome assemblies suffer from limited accuracy and robustness, requiring extensive manual editing. In addition, the currently available gold-standard TE databases are not comprehensive, even for extensively studied species, highlighting the critical need for an automated TE detection method to supplement existing repositories. In this study, we introduce HiTE, a fast and accurate dynamic boundary adjustment approach designed to detect full-length TEs. The experimental results demonstrate that HiTE outperforms RepeatModeler2, the state-of-the-art tool, across various species. Furthermore, …


Sccad: Cluster Decomposition-Based Anomaly Detection For Rare Cell Identification In Single-Cell Expression Data, Yunpei Xu, Shaokai Wang, Qilong Feng, Jiazhi Xia, Yaohang Li, Hong-Dong Li, Jianxin Wang Jan 2024

Sccad: Cluster Decomposition-Based Anomaly Detection For Rare Cell Identification In Single-Cell Expression Data, Yunpei Xu, Shaokai Wang, Qilong Feng, Jiazhi Xia, Yaohang Li, Hong-Dong Li, Jianxin Wang

Computer Science Faculty Publications

Single-cell RNA sequencing (scRNA-seq) technologies have become essential tools for characterizing cellular landscapes within complex tissues. Large-scale single-cell transcriptomics holds great potential for identifying rare cell types critical to the pathogenesis of diseases and biological processes. Existing methods for identifying rare cell types often rely on one-time clustering using partial or global gene expression. However, these rare cell types may be overlooked during the clustering phase, posing challenges for their accurate identification. In this paper, we propose a Cluster decomposition-based Anomaly Detection method (scCAD), which iteratively decomposes clusters based on the most differential signals in each cluster to effectively separate …


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 Jan 2024

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-Landau (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 (KDM5C). …


Identification And Characterization Of Two Novel Kcnh2 Mutations Contributing To Long Qt Syndrome, Anthony Owusu-Mensah, Jacqueline Treat, Joyce Bernardi, Ryan Pfeiffer, Robert Goodrow, Bright Tsevi, Victoria Lam, Michel Audette, Jonathan M. Cordeiro, Makarand Deo Jan 2024

Identification And Characterization Of Two Novel Kcnh2 Mutations Contributing To Long Qt Syndrome, Anthony Owusu-Mensah, Jacqueline Treat, Joyce Bernardi, Ryan Pfeiffer, Robert Goodrow, Bright Tsevi, Victoria Lam, Michel Audette, Jonathan M. Cordeiro, Makarand Deo

Electrical & Computer Engineering Faculty Publications

We identified two different inherited mutations in KCNH2 gene, or human ether-a-go-go related gene (hERG), which are linked to Long QT Syndrome. The first mutation was in a 1-day-old infant, whereas the second was in a 14-year-old girl. The two KCNH2 mutations were transiently transfected into either human embryonic kidney (HEK) cells or human induced pluripotent stem-cell derived cardiomyocytes. We performed associated multiscale computer simulations to elucidate the arrhythmogenic potentials of the KCNH2 mutations. Genetic screening of the first and second index patients revealed a heterozygous missense mutation in KCNH2, resulting in an amino acid change (P632L) in the …


Landscape Genetics Of The Gulf Coast Tick, Amblyomma Maculatum, Sara Simmons Benham May 2023

Landscape Genetics Of The Gulf Coast Tick, Amblyomma Maculatum, Sara Simmons Benham

Biological Sciences Theses & Dissertations

Connectivity among populations helps to maintain genetic diversity, population stability, and resilience. The Gulf Coast tick, Amblyomma maculatum, is a vector of the pathogen Rickettsia parkeri. Persistence of tick populations with high rates of R. parkeri infection poses health risks to humans and animals. Mitochondrial haplotypes were characterized by sequencing a fragment of the mitochondrial 16S rRNA gene. A comparative study of A. maculatum and Amblyomma americanum was conducted to identify similar and unique patterns between the species within the same region. Next, I compared A. maculatum sites across three different regions of the United States. This work …


Margalefidinium Polykrikoides Cyst Resuspension In The Lafayette River, A Sub-Tributary Of The Chesapeake Bay, Gabrielle Greaney, Eduardo Perez Vega, Katherine Crider, Dreux Chappell, Kimberly Powell, Richard Hale, Peter Bernhardt, Margaret Mulholland Mar 2023

Margalefidinium Polykrikoides Cyst Resuspension In The Lafayette River, A Sub-Tributary Of The Chesapeake Bay, Gabrielle Greaney, Eduardo Perez Vega, Katherine Crider, Dreux Chappell, Kimberly Powell, Richard Hale, Peter Bernhardt, Margaret Mulholland

Undergraduate Research Symposium

Harmful Algal Blooms are a collection of algae in a body of water that can cause serious environmental issues and health problems in both people and aquatic organisms. Dinoflagellates are microscopic, unicellular, and eukaryotic organisms that are well known for forming harmful algal blooms because of eutrophication. Coastal Virginia suffers from HABs in the Chesapeake Bay and its tributaries. A common species of dinoflagellate, known as Margalefidinium polykrikoides exists in the Chesapeake Bay. The purpose of this study is to determine if sediment resuspension produced by wind generated surface gravity waves cause cysts (dinoflagellate resting stages) to be suspended into …


Clonal Diversity, Antibiotic Resistance, And Virulence Factor Prevalence Of Community Associated Staphylococcus Aureus In Southeastern Virginia, Katelyn D. Cranmer, Mohan D. Pant, Suzanne Quesnel, Julia A. Sharp Jan 2023

Clonal Diversity, Antibiotic Resistance, And Virulence Factor Prevalence Of Community Associated Staphylococcus Aureus In Southeastern Virginia, Katelyn D. Cranmer, Mohan D. Pant, Suzanne Quesnel, Julia A. Sharp

EVMS School of Health Professions Faculty Publications

Staphylococcus aureus is a significant human pathogen with a formidable propensity for antibiotic resistance. Worldwide, it is the leading cause of skin and soft tissue infections (SSTI), septic arthritis, osteomyelitis, and infective endocarditis originating from both community- and healthcare associated settings. Although often grouped by methicillin resistance, both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) strains are known to cause significant pathologies and injuries. Virulence factors and growing resistance to antibiotics play major roles in the pathogenicity of community-associated strains. In our study, we examined the genetic variability and acquired antibiograms of 122 S. aureus clinical isolates from SSTI, blood, and urinary …


Gene Expression Under Combined Hypoxia And Acidosis In Chondrosarcoma, Michael Stacey, Kostika Vangjeli, Christopher Osgood Jan 2023

Gene Expression Under Combined Hypoxia And Acidosis In Chondrosarcoma, Michael Stacey, Kostika Vangjeli, Christopher Osgood

Bioelectrics Publications

Chondrosarcomas are the second most common cause of bone cancer and are removed surgically with wide margins. On recurrence, they are resistant to chemo and radiation therapy and new treatment options are critically required. This tumor type produces hyaline cartilage, a cartilage normally formed under hypoxic and acidic environment due to lack of vasculature in cartilage. Paradoxically, chondrosarcomas arise in the well vascularized, oxygen rich environment of the bone. Hypoxia and acidosis are two stressors where the cellular effects are typically reported separately even though cells experience combined effects of hypoxia and acidosis. Given the mechanistic links between hypoxia and …


Extracting High-Molecular Weight Dna From Cyanobacteria Using Promega's Wizard® Hmw Dna Extraction Kit With A Modified Protocol, Metis, Megan A. Hept, Lesley H. Greene Jan 2023

Extracting High-Molecular Weight Dna From Cyanobacteria Using Promega's Wizard® Hmw Dna Extraction Kit With A Modified Protocol, Metis, Megan A. Hept, Lesley H. Greene

Chemistry & Biochemistry Faculty Publications

Extraction of high molecular weight (HMW) DNA for long read sequencing with little to no fragmentation and high purity is difficult to acquire from cyanobacterial species. Here we describe a modified method of extraction using Promega's Wizard® HMW DNA Extraction Kit to acquire high molecular weight DNA from cyanobacterial species. The protocol used in the kit is the “3.D. Isolating HMW DNA from Gram-Positive and Gram-Negative Bacteria” protocol. During a key step in the protocol, the lingering remnants of the mucilage layer of the cyanobacterial species is removed, preventing it from sticking to the DNA pellet produced. This customized modification …


The Practice And Promise Of Temporal Genomics For Measuring Evolutionary Responses To Global Change, René D. Clark, Katrina A. Catalano, Kyra S. Fitz, Eric Garcia, Kyle E. Jaynes, Brendan N. Reid, Allyson Sawkins, Anthony A. Snead, John C. Whalen, Malin L. Pinsky Jan 2023

The Practice And Promise Of Temporal Genomics For Measuring Evolutionary Responses To Global Change, René D. Clark, Katrina A. Catalano, Kyra S. Fitz, Eric Garcia, Kyle E. Jaynes, Brendan N. Reid, Allyson Sawkins, Anthony A. Snead, John C. Whalen, Malin L. Pinsky

Biological Sciences Faculty Publications

Understanding the evolutionary consequences of anthropogenic change is imperative for estimating long-term species resilience. While contemporary genomic data can provide us with important insights into recent demographic histories, investigating past change using present genomic data alone has limitations. In comparison, temporal genomics studies, defined herein as those that incorporate time series genomic data, utilize museum collections and repeated field sampling to directly examine evolutionary change. As temporal genomics is applied to more systems, species and questions, best practices can be helpful guides to make the most efficient use of limited resources. Here, we conduct a systematic literature review to synthesize …


Anti-Tick Vaccine Candidate Subolesin Is Important For Blood Feeding And Innate Immune Gene Expression In Soft Ticks, Krittika Nandy, Comfort Tamakloe, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta Jan 2023

Anti-Tick Vaccine Candidate Subolesin Is Important For Blood Feeding And Innate Immune Gene Expression In Soft Ticks, Krittika Nandy, Comfort Tamakloe, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Subolesin is a conserved molecule in both hard and soft ticks and is considered as an effective candidate molecule for the development of anti-tick vaccine. Previous studies have reported the role of subolesin in blood feeding, reproduction, development, and gene expression in hard ticks. However, studies addressing the role of subolesin in soft ticks are limited. In this study, we report that subolesin is not only important in soft tick Ornithodoros turicata americanus blood feeding but also in the regulation of innate immune gene expression in these ticks. We identified and characterized several putative innate immune genes including Toll, Lysozyme …