Genetics and Genomics Commons^™

From Genes To Streams: Mitochondrial Approaches To Population Monitoring Of The Santa Ana Sucker Catostomus Santaanae, Mariana Antonio

Electronic Theses, Projects, and Dissertations

This study was developed to use aquatic environmental DNA (eDNA) as a tool to detect the presence of the Santa Ana sucker (Catostomus santaanae), a federally threatened fish species, across the Santa Ana River in Southern California. Environmental DNA is any genetic material that an organism sheds into the environment. We can get an idea of what aquatic species are present when sampling water at a given site. We sequenced the complete mitochondrial genome (mitogenome) of the Santa Ana sucker and designed custom DNA primers to improve eDNA detection accuracy. These primers were selected based on high genetic …

Biologically Informed Negative Samplingfor Antibody Chain Pairing Classification, Ishita Singh

Computer Science Senior Theses

Antibody heavy and light chain (H/L) pairing is fundamental to antigen recognition and stability. While single-cell sequencing preserves native pairing information, widely used bulk repertoire and spatial transcriptomics platforms do not, motivating the need for efficient ML methods to infer H/L pairing. Training a binary classifier for this task faces the methodological challenge of a lack of true biological negatives, since natural selection eliminates B cells with incompatible H/L pairs.

In this thesis, I introduce a biologically informed negative sampling strategy for H/L pairing classification, drawing on known V-gene biases in heavy and light chain pairing. Pseudo-negatives are constructed by …

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

UROP Posters

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

A Persistent Homology Framework For Scrna-Seq: Assessing Clustering Robustness And Quantifying Preprocessing And Integration Effects On Topological Features., Jonah Daneshmand

Electronic Theses and Dissertations

As single-cell RNA sequencing (scRNA-seq) data expands, robust methods for integrating diverse datasets are critical. This dissertation applies Persistent Homology (PH), a technique from Topological Data Analysis (TDA), to a collection of scRNA-seq datasets spanning eight tissue types to quantify how data integration affects topological features and biological interpretability. We assessed global topological structure using Betti curves, Euler characteristics, and persistence landscapes across raw, normalized, and integrated data representations. Our analysis revealed a performance inversion: while conventional methods excelled on unintegrated data, high-granularity topological methods, particularly those sensitive to global data structure, became superior after integration. This suggests a synergy …

Bioinformatic Analysis Of Pogz Variants In Relation To White Sutton Syndrome, Hannah Rollins

Theses

White-Sutton syndrome (WHSUS) is a rare neurodevelopmental disorder caused by mutations in the Pogo Transposable Element with ZNF Domain (POGZ) gene, which encodes pogo-transposable element with ZNF domain, a chromatin regulator essential for proper mitotic progression and DNA repair. This study uses a bioinformatic framework to evaluate the structural and functional impact of missense mutations in the conserved amino acid region (positions 500–800) of the POGZ protein. Protein modeling, variant effect prediction, conservation analysis, and molecular dynamics simulations were employed to gain an understanding of the effects of POGZ missense mutations on protein structure and movement with specific emphasis on …

Cazyme Gene Cluster Diversity In Human Gut Microbiome, Yi Xing

Department of Food Science and Technology: Dissertations, Theses, and Student Research

In gut microbiome research, carbohydrate-active enzyme gene clusters (CGCs) have emerged as key functional units for understanding microbial glycan degradation. Unlike taxonomic or broad pathway annotations, CGCs offer gene-cluster-level resolution and capture substrate-specific microbial functions. However, their diversity and distribution in relation to host metabolic phenotypes, such as obesity, remain poorly characterized. This study tests the hypothesis that the composition and abundance of fiber-targeting CGCs vary between obese and healthy human gut microbiomes, reflecting distinct microbial carbohydrate utilization strategies. To examine this, we constructed a high-quality reference CGC dataset comprising 94,019 clusters from the Unified Human Gastrointestinal Genome and profiled …

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 …

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 …

Discovery Of Suitable Habitat For Freshwater Mussel Species In The Appomattox River Through The Use Of Environmental Dna., Nicholas Duellman

Longwood Senior Thesis Proposal

Freshwater mussels are a keystone species providing crucial ecosystem services and river composition resiliency. Anecdotal evidence suggests the presence of freshwater mussels within the Appomattox river, the specifics of population sizes and suitable habitat remains an open question. Environmental DNA (eDNA) usage in conservation ecology has exploded in use within the past two decades, being far less invasive and cost-demanding than traditional methods. An eDNA metabarcoding pipeline of the 16s mitochondrial ribosomal subunit was built in R v. 4.4.2, using dada2 v. 3.2.1 package to trim MinION single read ASV outputs for freshwater mussel species identification in the interest of …

Examining Genomic Islands To Trace The Evolution Of The Urinary Microbiome, Elena G. Renshaw

Senior Theses

There has been a longstanding misconception that the healthy human urinary tract is sterile; however, increasing evidence demonstrates the presence of a dynamic resident urinary microbiota. Emerging research suggests that the urinary microbiota plays a protective role against urological symptoms and infection, but interactions between urinary bacterial species remain understudied. Genomic islands (GIs) are large DNA segments acquired through horizontal gene transfer between bacteria and can provide fitness advantages, particularly to uropathogens. This research utilizes 1,301 genome sequences isolated from urine samples representing the bacterial diversity found within the human urinary tract. GIs were annotated using IslandViewer 4 and TreasureIsland. …

Using Rna Sequencing To Examine Encephalic Gene Expression In Cactus Mice, Sarah A. Nicholls

Honors Theses and Capstones

Many of the exact mechanisms by which desert-adapted animals avoid dehydration-induced complications are unknown, though there are likely ties to the general mammalian dehydration response, a multisystem process spearheaded by the brain. Peromyscus eremicus, the cactus mouse, can survive its whole life without intaking water and is commonly used as a model to study desert adaptations. In this study, we have used bulk transcriptomics to characterize the differential gene expression across hydrated and dehydrated P. eremicus in five major regions of the brain: the cerebral cortex (referred to throughout much of this paper as the cortex), hippocampus, thalamus, midbrain, …

From Sequencing To Conservation: Genomic Analysis Of Three Sportfish Species In West Virginia, Andrew Johnson

Graduate Theses, Dissertations, and Problem Reports (ETD)

Situated in the Appalachian Mountains, one of the oldest mountain ranges on Earth, West Virginia waters boast rich ichthyofauna including native sportfish species walleye (Sander vitreus), largemouth bass (Micropterus nigricans), and muskellunge (Esox masquinongy). These three species are all native to the contemporary Ohio River watershed and play a major recreational and ecological role in local fisheries. Ecologically, all three species are apex predators and play a key role in ecosystems by directly influencing local fish assemblages. As dominant apex predators all three species are highly sought after in recreational fisheries with largemouth bass …

Methods In Statistics, Machine Learning, And Deep Learning For Combining Multi-Omics Dataset, Md Mutasim Billah

Dissertations, Master's Theses and Master's Reports

Transcriptome-wide association studies (TWAS) have emerged as a powerful strategy to bridge genome-wide association studies (GWAS) with gene regulatory mechanisms by integrating genotypic data with gene expression data. While early TWAS methods typically rely on linear models and single-tissue expression references, recent advances underscore the need for flexible, multi-tissue approaches that can capture heterogeneous regulatory architectures and tissue-specific expression patterns. This dissertation introduces a three‑part research project that advances multi‑tissue transcriptome‑wide association studies (TWAS) along complementary axes of methodology, statistical power, and modelling flexibility.

In chapter One, TWAS‑CTL introduces a two‑stage cross‑tissue learner that trains any user‑chosen single‑tissue imputers (STLs) …

Foundation Models In Bioinformatics, Fei Guo, Renchu Guan, Yaohang Li, Qi Liu, Xiaowo Wang, Can Yang, Jianxin Wang

Computer Science Faculty Publications

With the adoption of foundation models (FMs), artificial intelligence (AI) has become increasingly significant in bioinformatics and has successfully addressed many historical challenges, such as pre-training frameworks, model evaluation and interpretability. FMs demonstrate notable proficiency in managing large-scale, unlabeled datasets, because experimental procedures are costly and labor intensive. In various downstream tasks, FMs have consistently achieved noteworthy results, demonstrating high levels of accuracy in representing biological entities. A new era in computational biology has been ushered in by the application of FMs, focusing on both general and specific biological issues. In this review, we introduce recent advancements in bioinformatics FMs …

Benchmarking Batch-Effect Correction Methods Towards The Construction Of A Triple-Negative Breast Cancer Cell Atlas, Peter Scheible, Amy H. Tang, Jing He, Jiangwen Sun

Computer Science Faculty Publications

Triple-negative breast cancer (TNBC) requires detailed cellular mapping given its aggressive nature, immense tumor heterogeneity and genetic diversity. We integrated 156,794 cells from six scRNA-seq datasets—including tumors, metastases, and cell lines—to build a TNBC scRNA cell atlas, focusing on batch effect mitigation while maintaining biological and molecular details. Preprocessing f ilters noise, normalizes data, and leverages PCA for integration readiness. We utilized scANVI, a semi-supervised tool, to align datasets, preserving TNBC’s complex tumor heterogeneity via marker annotations [1]. UMAPs demonstrate biological clustering in integrated data, contrasted with datasetdriven unintegrated patterns. Assessments verifying effective batch correction. This method aligns with NASA’s …

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 …

Gene-Environment Interactions In Non-Alcoholic Fatty Liver Disease: Insights From Mexican American Populations, Eron G. Manusov, Vincent P. Diego, Marcio Almeida, Jacob Galan, Auwal A. Bala, Marco Arriaga, Natasha Garcia-Rodriguez, Renee Hernandez, Satish Kumar, John Blangero, Sarah Williams-Blangero

School of Medicine Publications

Nonalcoholic Fatty Liver Disease (NAFLD) is a prevalent and complex condition influenced by both genetic and environmental factors. This chapter explores the genotype-by-environment interactions that contribute to the development and progression of NAFLD in the Mexican American population. Using advanced genetic epidemiology and bioinformatics approaches, we investigated how specific genetic variants interact with environmental factors such as depression, acculturation stress, and social determinants of health, to influence NAFLD risk and severity. Our findings reveal significant genotype-by-environment interactions for key NAFLD-related traits, including HbA1c, AST/ALT ratio, and steatosis-controlled attenuation parameter (CAP). We also discuss the application of cutting-edge proteomic and transcriptomic …

Simulation Of Crispr-Cas9 Editing On Evolving Barcode And Accuracy Of Lineage Tracing, Fengshuo Liu, Xiang Zhang, Yipeng Yang

Faculty, Staff and Students Publications

We designed a simulation program that mimics the CRISPR-Cas9 editing on evolving barcode and double strand break repair procedure along with cell divisions. Emerging barcode mutations tend to build upon previously existing mutations, occurring sequentially with each generation. This process results in a unique mutation profile in each cell. We sample the barcodes in leaf cells and reconstruct the lineage, comparing it to the original lineage tree to test algorithm accuracy under different parameter settings. Our computational simulations validate the reasonable assumptions deduced from experimental observations, emphasizing that factors such as sampling size, barcode length, multiple barcodes, indel probabilities, and …

Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations and Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …

Comprehensive Single-Cell Atlas Of The Mouse Retina, Jin Li, Jongsu Choi, Xuesen Cheng, Justin Ma, Shahil Pema, Joshua R Sanes, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cellular heterogeneity by characterizing cell types across tissues and species. While several mouse retinal scRNA-seq datasets exist, each dataset is either limited in cell numbers or focused on specific cell classes, thereby hindering comprehensive gene expression analysis across all retina types. To fill the gap, we generated the largest retinal scRNA-seq dataset to date, comprising approximately 190,000 single cells from C57BL/6J mouse retinas, enriched for rare population cells via antibody-based magnetic cell sorting. Integrating this dataset with public datasets, we constructed the Mouse Retina Cell Atlas (MRCA) for wild-type mice, encompassing …

Transcriptomic Profiling Of Engineered Human Gene Integration In The Mouse Genome Following In Vitro Gene Editing, Ethan Potts, Made Harumi Padmaswari, Christopher Nelson

Biomedical Engineering Undergraduate Honors Theses

Gene replacement is a promising method of therapy for genetic diseases. However, safety and efficacy are areas that need more research. This experiment aims to use RNA sequencing and bioinformatic techniques to provide answers to these questions and provide direction to future studies to develop a gene replacement therapeutic. C2C12 mouse myoblast cells were transfected with a vector containing a CRISPR-Cas9 system and the Human Factor IX (hF9) gene in order to hijack target genes and integrate the hF9 gene. The two target genes, myoglobin (Mb) and creatine kinase (Ckm), were chosen for their high rate of expression and low …

Archaeal Diversity In The Anna's Hummingbird Microbiome, Lauren E. Chance

Honors Scholar Theses

The microbial communities that are present in and on vertebrates are collectively called the microbiome. The composition of a microbiome is dependent upon the host, the environment, and evolution. There has been extensive research on the bacterial composition of host-associated microbiomes, however, there has been much less work on the archaeal composition of host-associated microbiomes. Archaea have previously been assumed to primarily exist in extreme environments, but this may not be true and has been influenced by their generally low abundance and methodological difficulties in detection. It is possible they are consistent members of diverse host-associated microbiomes.

Archaea-specific PCR primers …

An Investigation Of Information Structures In Dna, Joel Mohrmann

Department of Electrical and Computer Engineering: Dissertations, Theses, and Student Research

The information-containing nature of the DNA molecule has been long known and observed. One technique for quantifying the relationships existing within the information contained in DNA sequences is an entity from information theory known as the average mutual information (AMI) profile. This investigation sought to use principally the AMI profile along with a few other metrics to explore the structure of the information contained in DNA sequences.

Treating DNA sequences as an information source, several computational methods were employed to model their information structure. Maximum likelihood and maximum a posteriori estimators were used to predict missing bases in DNA sequences. …

The Genomics Of Champ1: Insights Into Their Cell-Type Specificity And Developmental Trajectories, Zoe Marie Van Caugherty

MUSC Theses and Dissertations

Chromosome alignment maintaining phosphoprotein 1(CHAMP1) is a gene that encodes a zinc finger protein that is involved in in the maintenance of kinetochore-microtubule attachment and regulating chromosome segregation in mitosis. (Itoh et al., 2011) CHAMP1 mutations have been shown to be major risk factors for neurodevelopmental disorders (NDDs) and autism spectrum disorder (ASD).(Asakura et al., 2021; Isidor et al., 2016; Levy et al., 2022) Although there is information on the link between CHAMP1 mutations and NDD, the role of CHAMP1 in regulating processes of human cortical development, namely, neurogenesis, proliferation, and electrophysiological properties of newly born neurons, is unknown. This …

A Comparative Study Of A Non-Small Cell Lung Cancer Associated Egfr Missense Variant Of Uncertain Significance, Vanessa Mejia

Theses

Non-small cell lung cancer (NSCLC) is a form of lung cancer that can be driven by heightened activity of epidermal growth factor receptor encoded by the EGFR gene. Genetic variants in EGFR have been identified that lead to abnormal cell growth and tumorigenesis. The objectives of this study was to 1) determine if an EGFR variant of uncertain significance (VUS) associated with NSCLC is potentially damaging based on evaluation of the ortholog let-23 in the model organism, C. elegans, and 2) identify conserved missense VUS loci associated with NSCLC. Through ClinVar, the EGFR VUS c.845G>C(p.Gly282Ala) was identified in …

Enabling The Clinical Application Of Artificial Intelligence In Genomics: A Perspective Of The Amia Genomics And Translational Bioinformatics Workgroup, Nephi A Walton, Radha Nagarajan, Chen Wang, Murat Sincan, Robert R Freimuth, David B Everman, Derek C Walton, Scott P Mcgrath, Dominick J Lemas, Panayiotis V Benos, Alexander V Alekseyenko, Qianqian Song, Ece Gamsiz Uzun, Casey Overby Taylor, Alper Uzun, Thomas Nate Person, Nadav Rappoport, Zhongming Zhao, Marc S Williams

Faculty, Staff and Student Publications

OBJECTIVE: Given the importance AI in genomics and its potential impact on human health, the American Medical Informatics Association-Genomics and Translational Biomedical Informatics (GenTBI) Workgroup developed this assessment of factors that can further enable the clinical application of AI in this space.

PROCESS: A list of relevant factors was developed through GenTBI workgroup discussions in multiple in-person and online meetings, along with review of pertinent publications. This list was then summarized and reviewed to achieve consensus among the group members.

CONCLUSIONS: Substantial informatics research and development are needed to fully realize the clinical potential of such technologies. The development of …

Assessing The Utility Of Breast Cancer Polygenic Risk Scores And Association With Clinical Factors In A Population Of Breast Cancer Patients, John L. Slunecka

Dissertations and Theses

INTRODUCTION: Breast cancer (BC) is the most common cancer among women and is classified as a complex disease. Advances in population genomics have led to the development of polygenic risk scores (PRSs) with the potential to enhance current risk models, but replication is often limited. OBJECTIVE: We sought to assess the predictive capabilities of two high-powered BC PRSs in a sample population selected for breast cancer. In addition, the capacity of the PRSs to predict clinical variables that could improve BC screening and treatments was explored. METHODS: Two published PRS algorithms (313 vs 3820) were used to score female subjects …

Machine Learning And Rna Bioinformatics, Jason Rafe Miller

Graduate Theses, Dissertations, and Problem Reports (ETD)

The applied science of bioinformatics encompasses computational analysis of molecular biology data. Advances in genomics and DNA sequencing technology have enabled computational analysis of ribonucleic acids (RNAs), which play diverse and critical roles in most cells. To assist the study of human RNA, we trained machine learning models on RNA nucleotide sequences, devoid of domain knowledge. We built models that distinguish long non-coding lncRNA from protein-coding mRNA, and models that predict the cytoplasmic vs. nuclear preferences of lncRNAs. In a review of published lncRNA subcellular localization classifiers, we show that the commonly used validation protocol generates optimistic performance measures, and …

From Code To Crops: Harnessing Bioinformatics And Artificial Intelligence (Ai) In Agricultural Omics, Lakshay Anand

Theses and Dissertations--Plant and Soil Sciences

Global agricultural faces numerous challenges, such as climate change, resource limitations, novel pests and diseases, increasing costs, and the ever-increasing human population. To tackle these challenges, we need innovative strategies that combine new technologies and data analytics approaches to enhance agricultural output, promote sustainable methods, and optimize resource allocation. The key to this innovation lies in understanding the complex molecular web within plants that governs their growth, defense, and adaptability mechanisms. By mastering this molecular network, we can cultivate crops that are more resilient, sustainable, and suitable for different climatic terrains. Moreover, studying the symbiotic relationship between plants and microorganisms …

Genomic Characterization Of Adolescent And Young Adult Cancers: Investigation Of Ewing Sarcoma Susceptibility And Chornobyl Thyroid Tumors, Olivia Lee

Dissertations and Theses (Open Access)

Adolescent and young adult (AYA) cancers, diagnosed between the ages of 15 and 39, can exhibit distinctive genetic and molecular characteristics. Reported epidemiologic findings and treatment outcomes based on pediatric and adult cancer studies are often not suitable for application to the AYA population, underscoring the need for more thorough genomic research. Advances in sequencing technologies have enabled comprehensive analyses of complex genomic characteristics of AYA cancers, crucial for understanding the underlying biology of these malignancies. Here, I have utilized advanced sequencing techniques and integrated analytic approaches to describe important genomic features in two different AYA cancer types: Ewing Sarcoma …