Genetics and Genomics Commons^™

Topodino: Self-Supervised Topological Representation Learning For Neuronal Morphologies, Yasser Binbisher

Master's Theses

Neuronal cell types are categorized by transcriptomic identity, yet their morphological heterogeneity defies this classification. In response, researchers have adopted unsupervised graph representation learning as a tool to reveal morphological variation within single-class transcriptomic types. However, the complex geometry of neuronal morphology—especially long axons and dense dendrites—challenges graph neural networks, which struggle with message propagation across extended structures. To mitigate this, current approaches enforce sub-sampling on neuronal graphs and omit axons entirely, sacrificing critical biological features for computational efficiency. To overcome this trade-off, this thesis introduces TopoDINO, a self-supervised, topology-aware representation learning model designed to preserve the full hierarchical organization …

Investigating A Link Between Dna Repair And Dna Replication In Escherichia Coli Using A Bacterial Two-Hybrid System, Lo Cooper

University Honors Theses

Cells rely on nucleotide excision repair (NER) to remove bulky DNA lesions, such as those caused by UV light. In Escherichia coli, NER involves the UvrABC complex, and includes two main pathways, global genomic repair and transcription-coupled repair (TCR). While TCR, which preferentially removes lesions that block RNA polymerase on the transcribed strand of active genes, is well studied, less is known about whether a similar coupling between repair proteins and replisomes blocked by damaged DNA exists. Such a process has been suggested by a high throughput interactome study, using the replisome subunit HolC as bait and the damage …

Genetic Analysis Of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk And Unique Genomic Associations, Cuihua Xia, Ney Alliey Rodriguez, Carol A. Tamminga, Matcheri S. Keshavan, Godfrey Pearlson

School of Medicine Publications

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples. Applied to schizophrenia PRS, we found the Khera AAPRS method to show superior portability and comparable prediction accuracy as compared with the Ge method. The three Biotypes of psychosis disorders had similar AAPRSs across ancestries. In genomic analysis of Biotypes, 12 genes, …

Exploring Natural Competence Of Escherichia Coli Through Biofilm Formation, Thulni Liyanaarachchi

University Honors Theses

Escherichia coli is a species not known for natural competence; however, specific growth conditions can induce the process in this bacterium due to the presence of homologous competence genes. These conditions could be met with biofilm formation through an active growth phase in the two-layer architecture. Therefore, my thesis examined whether natural competence is exhibited in E. coli during biofilm formation as determined by the genetic transfer of ampicillin and chloramphenicol-resistance genes between two separate strains. The experiments were broken into three aims to determine the morphology of the biofilm in inter-strain co-cultures and cell-DNA mixes, the effect of …

A Scan Of Pleiotropic Immune Mediated Disease Genes Identifies Novel Determinants Of Baseline Fviii Inhibitor Status In Hemophilia A, Marcio Almeida, Vincent P. Diego, Kevin R. Viel, Bernadette W. Luu, Eron G. Manusov, Juan M. Peralta, Satish Kumar, Sarah Williams-Blangero, John Blangero, Tom Howard

School of Medicine Publications

Hemophilia-A (HA) is the X-linked bleeding disorder caused by heterogeneous factor (F)VIII gene (F8)-mutations and deficiencies in plasma-FVIII-activity that prevent intrinsic-pathway mediated coagulation-amplification. Severe-HA patients (HAPs) require life-long infusions of therapeutic-FVIII-proteins (tFVIIIs) but ~30% develop neutralizing-tFVIII-antibodies called “FVIII-inhibitors (FEIs)”. We investigated the genetics underlying the variable risk of FEI-development in 450 North American HAPs (206 and 244 respectively self-reporting black-African- or white-European-ancestry) by analyzing the genotypes of single-nucleotide-variations (SNVs) in candidate immune-mediated-disease (IMD)-genes using a binary linear-mixed model of genetic association with baseline-FEI-status, the dependent variable, while simultaneously accounting for their genetic relationships and heterogeneous-F8-mutations to …

Analytical Approaches For Identification Of Essential Genomes Of Plasmodium Knowlesi And Babesia Divergens, Sida Ye

Graduate Doctoral Dissertations

Apicomplexa constitute a large phylum of single-celled, obligate intracellular protozoan parasites. Notably, Plasmodium spp. and Babesia spp. are apicomplexan parasites that infect red blood cells. Plasmodium species are the causative agent of malaria and are transmitted by Anopheles mosquitoes, affecting large human populations, whereas Babesia spp., transmitted through the bite of Ixodes ticks cause babesiosis.

In this dissertation, we investigate the essential genome of these parasites using high-throughput transposon mutagenesis. Identifying the essential genome is key to finding new drug targets and understanding resistance mechanisms, a crucial pursuit given the rising resistance to frontline antimalarial drugs and the challenges …

Comparative Methylation Analyses Across Juglans Species To Investigate Epigenetic Contributions To Fungal Resistance, Keertana Chagari

Honors Scholar Theses

Juglans cinerea (butternut) is a critically threatened North American tree species experiencing severe declines due to the fungal pathogen Ophiognomonia clavigignentijuglandacearum. In contrast, its Asian relative, Juglans ailantifolia (Japanese walnut), shows natural resistance. To investigate the genomic and epigenetic factors underlying this difference, we constructed and analyzed high-quality, chromosome-level genome assemblies for both species from long-read sequencing data (J. ailantifolia: 527Mb; J. cinerea: 586Mb), focusing on transposable element (TE) content, DNA methylation patterns, and regulation of pathogen resistance genes (PRGs).

Repeat analysis revealed that J. cinerea has a slightly higher overall transposable element (TE) content, with …

Integrating Radiogenomics And Machine Learning In Musculoskeletal Oncology Care, Rahul Kumar, Kyle Sporn, Akshay Khanna, Phani Paladugu, Chirag Gowda, Alex Ngo, Ram Jagadeesan, Nasif Zaman, Alireza Tavakkoli

Department of Medicine Faculty Papers

Musculoskeletal tumors present a diagnostic challenge due to their rarity, histological diversity, and overlapping imaging features. Accurate characterization is essential for effective treatment planning and prognosis, yet current diagnostic workflows rely heavily on invasive biopsy and subjective radiologic interpretation. This review explores the evolving role of radiogenomics and machine learning in improving diagnostic accuracy for bone and soft tissue tumors. We examine integrating quantitative imaging features from MRI, CT, and PET with genomic and transcriptomic data to enable non-invasive tumor profiling. AI-powered platforms employing convolutional neural networks (CNNs) and radiomic texture analysis show promising results in tumor grading, subtype differentiation …

The Role Of G6pd Variants And 3d Genomic Structure In The Development Of Pulmonary Hypertension, Christina M. Signoretti Ph.D.

NYMC Student Theses and Dissertations

Pulmonary hypertension is an under-recognized global health epidemic which is estimated to affect 1% of the population. It is associated with sustained mean pulmonary artery pressure greater than 20 mmHg, pulmonary artery remodeling, smooth muscle and endothelial cell proliferation and subsequent increased right ventricle hypertrophy due to increased afterload. Glucose-6-phosphate dehydrogenase (G6PD) is one of the key enzymes in the pentose phosphate pathway and has been previously linked to the development of pulmonary hypertension. G6PD deficiency is the most common human enzymopathy which affects approximately 400 million people worldwide and is a result of agricultural and epidemiological evolution in different …

Sexual And Vegetative Recruitment Of Trembling Aspen Following A High-Severity Boreal Wildfire, Denyse A. Dawe, Ellen Whitman, Michael Michaelian, Alan J. Tepley, Marc-André Parisien

Aspen Bibliography

Background High-severity fire is rare in trembling aspen-dominated forests of the boreal region. The post-fire recruitment strategy of aspen, by either vegetative suckering or sexually (i.e., by seed), has considerable implications for subsequent forest structure, genetic diversity, and ecological resilience to shifting climatic and disturbance regimes. In this study, we take advantage of the unique opportunity provided by the Chuckegg Creek Wildfire Fire (310,000 ha) in northern Alberta, Canada, which burned at high severity through aspen stands before and after spring green-up, to document how phenology, fire severity, and stand characteristics affect recruitment one year following the fire.

Results We …

Factors Impacting The Variability Of Post-Fire Forest Regeneration In Central European Pine Plantations, Florent Jouy, Maren Schüle, Yojana Adhikari, Anja Binder, Danica Clerc, Werner Gerwin, Thilo Heinken, Thomas Raab, Frank Repmann, Susanne Rönnefarth, Marina Schirrmacher, Marie-Therese Schmehl, Jens Schröder, Pierre L. Ibisch

Aspen Bibliography

Fire is increasingly posing a risk to forests and plantations, even in the temperate latitudes of central Europe. Little is known about fire ecology in this region, and therefore, appropriate approaches for the management and reforestation of burned sites are mostly lacking. In a Scots pine plantation region in Brandenburg (northeast Germany), the early tree regeneration of two nearby areas that burned 1 year apart was investigated. We observed that 3 years after the fire events, the forest in one study area showed a relatively high regeneration with a mean density of 7765 saplings/ha, clearly dominated by European aspen (93%); …

Network Analysis Of Antimicrobial Resistance In Staphylococcus Aureus: Characterization Of Hub Genes And Their Functional Implications, Md Imran Hasan, Davida Smyth, Jeong Yang, Ashley Teufel

Masters Theses (Archived)

Antimicrobial resistance is a major cause of morbidity and mortality in patients with S. aureus infections. In this study, we analyzed genes, molecular mechanisms, and pathways driving drug resistance in S. aureus using network analysis. Using whole-genome sequencing (WGS) data and systems biology approaches, we identified 229 AMR-associated genes and constructed a protein-protein interaction network among these genes. Through network topology and functional enrichment analyses, we not only confirmed their association with resistance, but also highlighted the central roles of these genes in resistance pathways, such as efflux, target replacement, and target protection, which are directly linked to multiple drug …

A Phylogenomic Investigation Of The Historical Biogeography Of Livebearers (Cyprinodontiformes: Poeciliidae), Sheila Rodríguez Machado

LSU Doctoral Dissertations

The Neotropics contain several biodiversity hotspots and harbor the highest diversity of freshwater fishes globally. Yet, recognizing the patterns and processes driving this richness remains a challenge. Similarly, all groups and subregions have not received the same attention, especially in the genomics era. Addressing these knowledge gaps will help us to better understand the region’s evolutionary and biogeographic complexity. The goal of this dissertation is to examine phylogenetic and biogeographic patterns of Neotropical freshwater fishes, with emphasis on the Greater Antilles, across multiple taxonomic and geographic scales. To achieve this goal, I generated a genomic dataset of hundreds of ultraconserved …

Causes Of Heterozygosity Excess: The Case Of Mexican Populations Of Populus Tremuloides, Javier Hernández-Velasco, José Ciro Hernández-Díaz, Sergio Leonel Simental-Rodríguez, Juan P. Jaramillo-Correa, David S. Gernandt, José Jesús Vargas-Hernández, Ilga Porth, Roos Goessen, M. Socorro Gonzáles-Elizondo, Matthias Fladung, Cuauhtémoc Sáenz-Romero, José Guadalupe Martínez-Ávalos, Artemio Carrillo-Parra, Eduardo Mendoza-Maya, Arnulfo Blanco-García, Christian Wehenkel

Aspen Bibliography

The presence of heterozygous individuals in a population is crucial for maintaining genetic diversity, which can positively affect fitness and adaptability to environmental changes. While inbreeding generally reduces the proportion of heterozygous individuals in a population, polyploidy tends to increase the proportion. North American Populus tremuloides is one of the most widely distributed and ecologically important tree species in the Northern Hemisphere. However, genetic variation in Mexican populations of P. tremuloides, including the genetic signatures of their adaptation to a variety of environments, remains largely uncharacterized. The aim of this study was to analyze how inbreeding coefficient (F …

Sex, Skulls, And Selection: An Exploration Of Blakely Island's Deer Population And Their Ecology Through Genetic Sex Differentiation Of Juvenile Crania, Blair P. Graves

Honors Projects

As an isolated landmass with no natural predators, Blakely Island serves as an effective study site for the study of evolutionary factors relating to insular populations of large mammals. A disparity in the adult sex ratio of local deer has been observed, but the demographics of juveniles must still be ascertained through genetic methods. This study aims to further research concerning the development of a replicable and non-toxic procedure through which undergraduate students can identify the sex of numerous juvenile deer crania. Specifically, differing decalcification lengths, DNA extraction kit methods, and amelogenin primer sets were evaluated for relative success in …

Endophenotype-Informed Association Analyses For Liver Fat Accumulation And Metabolic Dysfunction In The Fels Longitudinal Study, Ariana L. Garza, John Blangero, Miryoung Lee, Cici X. Bauer, Stefan A. Czerwinski, Audrey Choh

School of Medicine Publications

The identification of causal genomic regions for liver fat accumulation in the context of metabolic dysfunction remains a challenging goal. This study aimed to identify potential endophenotypes for liver fat content and employ them in bivariate linkage searches for pleiotropic genetic regions where targeted association analysis is more likely to reveal significant variants. Multiple metabolic risk and adiposity distribution traits were assessed using the endophenotype ranking value. The top-ranked endophenotypes were then used in a bivariate linkage analysis, paired with liver fat content. Quantitative trait loci (QTLs) identified as significant or suggestive were targeted for measured genotype association analyses. The …

Diagnostic And Clinical Utility Of Oncoscan Microarray And Ngs-Based Sequencing In Pediatric Solid Tumors: Children’S Mercy Hospital’S Experience, Aravindh Nagarajan, Lisa Lansdon, Midhat Farooqi, Lei Zhang, Elena Repnikova

Research Days

This papers attempts to evaluate the diagnostic and clinical utility of microarray-based OS+ in detecting clinically relevant genetic alterations in FFPE solid tumor samples and to compare the yield of somatic mutation detection by WGS/WES in pediatric solid tumors at Children’s Mercy Hospital - Kansas City.

Generation Of A Transgenic Vector For The Purpose Of Transforming Charcoal Rot Resistance Into Soybeans (Glycine Max), John M. Bear Jr

Electronic Theses & Dissertations

Charcoal rot, caused by Macrophomina phaseolina, is among the most devastating fungal pathogens affecting G. max, particularly in drought-susceptible regions such as the midwestern United States. Traditional agricultural practices have included crop rotation and irrigation, which have proved ineffective or economically unfeasible. Charcoal rot infects over 500 other species of plants and can overwinter as dormant sclerotia which can germinate once soybeans are re-planted and infect young plants. As a result, transgenic solutions have offered a promising alternative for the development of disease-resistant soybeans. This thesis documents the construction of a transgenic vector to express BOZO, a …

Mechanisms That Contribute To Age-Dependent Segregation Errors In Drosophila Oocytes, Zihan Meng

Dartmouth College Ph.D Dissertations

Meiotic chromosome segregation errors in human oocytes are the leading cause of miscarriages and aneuploid pregnancies, and these errors increase dramatically as women age. Using Drosophila oocytes as a model system, this dissertation identifies the NAD⁺-dependent deacetylase Sirt1 as a key regulator of chromosome segregation and meiotic arm cohesion. Loss of Sirt1 activity during meiotic prophase leads to premature loss of arm cohesion and increased segregation errors in Drosophila oocytes. In addition, elevated acetylation of its substrate, histone H4K16, indicates that Sirt1 activity declines in oocytes during aging. Strikingly, dietary administration of the Sirt1 activator SRT1720 preserves Sirt1 deacetylase activity …

Investigating The Influence Of Environmental Stressors To Exopolysaccharide Production In Soil Cyanobacteria: Genomic And Physiological Perspectives, Benjy Sedano-Herrera

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cyanobacteria are photosynthetic microbes with essential roles in Earth’s ecosystems. The secretion of long–chain polysaccharides, known as exopolysaccharides (EPS), is a key trait facilitating cyanobacterial adaptation to diverse ecosystems. Genomics studies have shown that aquatic cyanobacteria harbor multiple gene copies encoding EPS export proteins, likely conferring a selective advantage in lakes or oceans. In addition, physiological experiments showed that nutrient limitation in aquatic habitats influences EPS production, affecting cyanobacterial fitness. However, whether terrestrial cyanobacteria also harbor multiple EPS-related genes and how nutrient limitation impacts their EPS production is not well understood.In the first chapter of my thesis, we investigated the …

Identification Of Methylation Patterns, Associated Dna Methylating Proteins, And Methyltransferase Inhibitors On The Promoter Regions Of Dax-1, Brandon Tyler Toy

Master's Theses

The DAX-1 gene (Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1) encodes for an orphan nuclear hormone receptor and its mutation is implicated in multiple diseases including congenital adrenal hypoplasia, adrenal cancer, and breast cancer. Previous research has linked DAX-1 downregulation to tumor initiation in breast tissue, suggesting the gene acts as a tumor suppressor with respect to breast cancer. Additional studies completed by the Tzagarakis-Foster laboratory have shown that methylation of the DAX-1 promoter region is heavily influential in breast cancer development, with release of epigenetic repression resulting in slowing of cellular proliferation …

Early Hematopoietic Differentiation Of An Inducible Pluripotent Stem Cell Model Of Infant Lymphoblastic Leukemia, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Priyanka Kumar, Jay L. Vivian, John M. Perry

Research Days

This abstract describes our work regarding the differentiation of human inducible pluripotent stem cells into hematopoietic stem and progenitor cells as the groundwork for the development of a genomics driven inducible pluripotent stem cell model of KMT2A rearranged infant acute lymphoblastic leukemia.

In The Quest For New Horizons: Evaluating Novel Therapeutic Approaches For Tuberculosis Treatment, Selassie Mawuko, Aminata Traore, Bibi-Sakeena Khemraj, Anna Steto, Richa Gupta

Publications and Research

Tuberculosis (TB) in humans, caused by Mycobacterium tuberculosis, is a significant global health concern, resulting in high disease burden and mortality each year which together make it the world’s topmost infectious killer. The emergence of multidrug-resistant tuberculosis (MDR-TB) in recent decades has further exacerbated the present situation and warrants an urgent need to develop and investigate innovative treatment regimes. This study aims to assess the therapeutic potential of newly identified drug candidates, namely Bedaquiline, Delamanid, and Linezolid, in treating MDR-TB. We adopted a consolidated and integrated approach encompassing a thorough literature review, empirical experimental studies, multiple sequence alignments, and …

The Role Of Presynaptic Proteins In Alcohol Sensitivity And Tolerance, Madhumitha Gundluru

Honors Theses

Mammalian Unc13 (Munc13) and Drosophila Unc13 (Dunc13) are presynaptic active zone proteins essential for synaptic vesicle docking and priming in a neuron. Alcohol binds to the C1 domain of Munc13, which inhibits DAG binding. The reduction in DAG binding by Munc13 decreases the probability of vesicle fusion with the membrane, decreasing neurotransmitter release. Heterozygotes for a Dunc13 loss-of-function allele are behaviorally resistant to alcohol, physiologically resistant to alcohol, molecularly resistant to alcohol, and self-administer significantly more alcohol than control flies. Therefore, genetically reducing Dunc13 mimics a state of alcohol tolerance in the fly. The two main Dunc13 isoforms, Dunc13A and …

Investigating The Effects Of Transcription Factor Binding And Genetic Variants In The Striatum Of Post-Mortem Cohorts With Opioid Use Disorder, Rajashree Chakraborty

Theses & Dissertations

The opioid crisis has emerged as one of the most pressing public health challenges of our time, with Opioid Use Disorder (OUD) affecting millions of lives across the globe. Studying OUD is not merely an academic pursuit but a critical necessity in addressing this multifaceted epidemic. The urgency of this research is underscored by the staggering prevalence of OUD, with an estimated 3.7% of U.S. adults requiring treatment in 2022 alone. Despite the availability of effective medications for OUD, a significant treatment gap persists, with only a quarter of those in need receiving these life-saving interventions. The far-reaching consequences of …

Mesoderm-Specific Transcript Has A Role In The Systemic Regulation Of Obesity, Maria J. Orellana Rosales

Thinking Matters Symposium

Mesoderm specific transcript (Mest) expression in white adipose tissue (WAT) is variable in genetically identical mice. Previous studies have shown a connection between Mest high expression and propensity for fat mass expansion. WAT and liver crosstalk has been well documented with hormone-like peptides signaling and regulating important metabolic pathways. The aim of this study is to investigate the correlation between these circulating factors and Mest expression in mice after exposure to a high fat diet (HFD). A group of 120 C57B6/J mice, males and females, were exposed to a HFD (Western Diet, 40 kcal% fat) for 4 weeks (8-12 weeks …

Genome Annotation Of Stargaze, Madison R. Murray

Honors Theses

Bacteriophages are viruses which solely infect bacteria. They are one of the most abundant and diverse biological entities, yet there is a limited amount of information on these viruses, including their gene functions. Several previously unknown phages have been discovered including Stargaze, whose bacterial host is Mycobacterium Smegmatis. Characterization of phage genes and their functions deepen our understanding of phages and potentially contribute to the broader biomedical effort associated with phages ability to combat bacterial infections. Stargaze is a G5 subcluster phage and it only has one other related phage in its cluster, that phage is from Madagascar. Using a …

Sirt6 Deficiency Promotes Senescence And Age-Associated Intervertebral Disc Degeneration In Mice, Pranay Ramteke, Bahiyah Watson, Mallory Toci, Victoria Tran, Shira N Johnston, Maria Tsingas, Ruteja Barve, Ramkrishna Mitra, Richard Loeser, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain. While the etiological factors for disc degeneration vary, age is still one of the most important risk factors. Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health, however its role in the intervertebral disc health remains unexplored. We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc (Acan^CreERT2; Sirt6^fl/fl). Histological studies showed a degenerative phenotype in knockout mice …

Performance Of Lasso And Ridge Regression For Variable Selection In Genome-Wide Association Studies Of Maize Flowering Time, Dipok Deb

Data Science and Data Mining

Genome-Wide Association Studies (GWAS) are instrumental in identifying genetic variants linked to complex traits, providing valuable insights into trait heritability and biological mechanisms. This study applies GWAS to investigate flowering time in maize, a critical adaptive trait, using a diverse dataset of 5,000 recombinant inbred lines across eight environments. Traditional GWAS methods often encounter challenges in high-dimensional datasets due to the presence of multiple small-effect genetic loci. To address this, we compared two penalized regression methods—LASSO and Ridge regression—to perform variable selection and regression analysis within a GWAS framework. LASSO effectively reduced the number of predictors by selecting the most …

Lifespan Reference Curves For Harmonizing Multi-Site Regional Brain White Matter Metrics From Diffusion Mri, Alyssa H. Zhu, Talia M. Nir, Shayan Javid, Julio E. Villalón-Reina, Amanda L. Rodrigue, Lachlan T. Strike, Greig I. De Zubicaray, Katie L. Mcmahon, Margaret J. Wright, John Blangero

School of Medicine Publications

Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3–95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data …