Genomics Commons^™

Toward Interpretable Multi-Omics Multimodal Biomedical Artificial Intelligence, Yanjun Lyu

Computer Science and Engineering Dissertations

The complexity of human disease arises from biological processes that unfold across multiple scales, from molecular variation through cellular function, tissue organisation, brain phenotypes, each of which is associated with distinct measurement modalities, regularities, and characteristic. Contemporary biomedical artificial intelligence has brought the opportunity to reveal the complexity with in; however, its methodological default, in which models are trained on most readily available modality, does not adequately engage with the multi-scale connected structure by which biological meaning is constituted. The research area of multi-omics and multi-modal AI for biomedicine remains at an early exploratory stage, and the work presented in …

Regulation Of Chromatin Remodeling By The Post-Hsa Domain Of Brg1, A Subunit The Baf Atp-Dependent Chromatin Remodeling Complex, Min Sze Ewe

Theses & Dissertations

The ATP-dependent chromatin remodeler BAF complex regulates nucleosome positioning, chromatin accessibility, and tissue specific gene expression. Its catalytic subunit, BRG1, contains several regulatory domains including the post-HSA region, proposed to modulate ATPase activity. Multiple cancer-associated mutations map to these regulatory regions underscoring their importance, yet the precise role of the post-HSA region in chromatin remodeling remains poorly understood.

To investigate the function of the post-HSA domain, we ectopically expressed FLAG-tagged BRG1 with post-HSA deletion (Δpost-HSA BRG1) in mouse embryonic stem cells. Western blot analysis confirmed expression of the mutant protein. To determine the effects of mutant protein expression on chromatin …

Genetic Characterization And High-Resolution Total Mrna Sequencing Of The Millipede Cherokia Georgiana Bollman, 1889, Elena Cruz

Biology Theses

There are approximately 12,000 described species within the class Diplopoda. Only six species, falling within four of sixteen orders, have fully sequenced genomes. No whole genomes are available for incredibly diverse families like Xystodesmidae. Many interesting characteristics in this group are poorly defined at the genetic level, such as the production of a defensive hydrogen cyanide secretion and UV fluorescence in the order Polydesmida. Here, we present a genetic characterization of the polydesmid millipede Cherokia georgiana Bollman, 1889. We include tissue-specific sequencing metrics, alignment and assembly of mitochondrial DNA consensus sequence according to tissue type, and phylogenetic tree construction using …

Update To: Advancing Butterfly Systematics Through Genomic Analysis, Jing Zhang, Qian Cong, Jinhui Shen, Leina Song, Nick Grishin

The Taxonomic Report of the International Lepidoptera Survey

In this update, we propose (type species or type localities in parentheses): Lochris Grishin, nom. nov. (Lasaia oileus Godman, 1903; Lepidoptera: Riodinidae) as a new substitute name for Locris Grishin, 2025 preoccupied by Locris Stål, 1866 (Cercopis rubra Fabricius, 1794; Hemiptera: Cercopidae), 5 new species, and 5 new subspecies: Emesis (Mandania) mandarina Grishin, sp. n. (Brazil: Santa Catarina) and Emesis (Mandania) mandela Grishin, sp. n. (Venezuela, Carabobo) in Riodinidae Grote, 1895 (1827); others in Hesperiidae Latreille, 1809: Telegonus (Rhabdoides) flavifimbro Grishin, sp. n. (Colombia), Urbanus (Urbanoides) dolus Grishin, sp. n. (Colombia: …

Elucidating The Multi-Omics Of Early-Onset Colorectal Cancer, Jumanah Alshenaifi

Dissertations and Theses (Open Access)

The incidence and mortality rates of sporadic early-onset colorectal cancer have increased in recent decades, but there is no clear etiological basis for this trend. EOCRC is commonly defined as colon and rectal cancers diagnosed before the age of 50 years. The rising incidence of EOCRC has made it the second most common cancer and the third leading cause of cancer death in this age group. The rising incidence of EOCRC is also documented internationally in more than 20 countries across different continents. Clinically, EOCRC has a distinct, more aggressive clinical profile than LOCRC. While approximately 15% of EOCRC cases …

A Stakeholder-Informed Conceptual Framework For Evaluating Genomics In Precision Oncology, Julie A. Wiedower

All Dissertations

This dissertation explores the value of genomic testing in precision oncology with an emphasis on how US payers conceptualize and prioritize elements of value. This research aims to address gaps in understanding payer perspectives and proposes a stakeholder-informed framework for evaluating genomic testing in oncology. To achieve this aim, the presented research investigates payer perspectives, value-based cancer care priorities, and the conceptual understanding of the value of a genetic diagnosis to establish a framework for value with the payer audience in mind. Chapter 1 outlines relevant background information relating to the genomic revolution and challenges in translating genomic testing technologies …

Hierarchical Lineage Tracing To Unravel Mechanisms Of Cancer Treatment Resistance, Rachel Danielle Saxe

Dartmouth College Ph.D Dissertations

Cancer cells adapt to treatment, leading to the emergence of clones that are more aggressive and resistant to anti-cancer therapies. We have a limited understanding of the development of treatment resistance as we lack technologies to map the evolution of cancer under the selective pressure of treatment. To address this, we developed a hierarchical, dynamic lineage tracing method called FLARE (Following Lineage Adaptation and Resistance Evolution). We use this technique to track the progression of acute myeloid leukemia (AML) cell lines through exposure to Cytarabine (AraC), a front-line treatment in AML, in vitro and in vivo. We map distinct cellular …

Analysis Of Chromatin Accessibility Changes In Endothelial Cells Exposed To Plastic Contaminants, Mikhail Y. Salnikov, Carly Boye, David B. Witonsky, Gabrielle Garlicki, Adnan Alazizi, Francesca Luca, Roger Pique-Regi

Medical Student Research Symposium

Degradation products from everyday plastic products are known to bioaccumulate and have also been shown to contaminate drinking water and food sources. BPA and phthalates are endocrine disrupting chemicals and plastic components that have previously been associated with endothelial cell dysfunction, atherosclerotic and other adverse cardiovascular events. However, there is a limited understanding of the mechanisms underlying these associations, such as genome-wide chromatin accessibility changes in endothelial cells exposed to these compounds. The purpose of this study is to explore genome-wide changes in chromatin accessibility associated with plastic exposure, as well as the discovery of transcription factor binding motifs dysregulated …

Gene Model For The Ortholog Of Glys In Drosophila Simulans, Madeline L. Gruys, Madison A. Sharp, Zachary Lill, Caroline Xiong, Amy T. Hark, James J. Youngblom, Chinmay P. Rele, Laura K. Reed

Faculty Journal Articles

Gene model for the ortholog of glycogen synthase ( Glys ) in the Drosophila simulans May 2017 (Princeton ASM75419v2/DsimGB2) Genome Assembly (GenBank Accession: GCA_000754195.3 ). This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

Snake Venoms As Models For Understanding The Origins And Evolution Of Gene Regulatory Networks, Siddharth S. Gopalan

Biology Dissertations - Archive

Understanding the relationship between genotype and phenotype is a fundamental goal of biology. However, the vastly complex nature of eukaryotic gene regulation can make deriving precise relationships between genotype and phenotype challenging. The gene regulatory architecture of snake venom systems provide an opportunity to study this problem in a phenotypic system with immense variation in phenotypes and the underlying genetics. Using a set of integrated functional genomic approaches with snake venoms as a central model, in this dissertation, I provide several examples of the regulatory mechanisms by which diversity in phenotypes arises. Specifically, I identify how gene expression heterogeneity between …

A Bayesian Deep Segmentation Framework For Glioblastoma Tumor Segmentation Using Follow-Up Mris, Tanjida Kabir, Kang-Lin Hsieh, Luis Nunez, Yu-Chun Hsu, Juan C Rodriguez Quintero, Octavio Arevalo, Kangyi Zhao, Jay-Jiguang Zhu, Roy F Riascos, Mahboubeh Madadi, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

Background: Glioblastoma (GBM) is the most common malignant brain tumor with an abysmal prognosis. Since complete tumor cell removal is impossible due to the infiltrative nature of GBM, accurate measurement is paramount for GBM assessment. Preoperative magnetic resonance images (MRIs) are crucial for initial diagnosis and surgical planning, while follow-up MRIs are vital for evaluating treatment response. The structural changes in the brain caused by surgical and therapeutic measures create significant differences between preoperative and follow-up MRIs. In clinical research, advanced deep learning models trained on preoperative MRIs are often applied to assess follow-up scans, but their effectiveness in this …

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 …

Project Give: Using A Virtual Genetics Service Platform To Reduce Health Inequities And Improve Access To Genomic Care In An Underserved Region Of Texas, Blake Vuocolo, Roberta Sierra, Daniel Brooks, Christopher Holder, Lauren Urbanski, Keila Rodriguez, Jose David Gamez, Surya Narayan Mulukutla, Ana Hernandez, Alberto Allegre, Humberto Hidalgo, Sarah Rodriguez, Sandy Magallan, Jeremy Gibson, Juan Carlos Bernini, Melanie Watson, Robert Nelson, Lizbeth Mellin-Sanchez, Nancy Garcia, Lori Berry, Hongzheng Dai, Claudia Soler-Alfonso, Kent Carter, Brendan Lee, Seema R Lalani

Faculty, Staff and Students Publications

BACKGROUND: The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley (RGV) at the Texas-Mexico border is predominantly Hispanic/Latino with a high poverty rate and very limited access to genetic services. Funded by the National Center for Advancing Translational Sciences, Project GIVE (Genetic Inclusion by Virtual Evaluation) was launched in 2022 to reduce the time to diagnosis and increase provider knowledge of genomics in this region, with the goal of …

Genomic Data Science Approaches For Understanding Human Diseases, Snehal Shah

All Dissertations

The intricate interplay of genetic predisposition, environmental influences, and lifestyle acts as the multifactorial landscape of diseases. Understanding this complexity presents a significant challenge. Molecular insights into disease mechanisms, particularly the interactions of DNA, RNA, and proteins with environmental and lifestyle factors, have revolutionized disease diagnosis, prognosis, and treatment. High-throughput technologies, such as next-generation sequencing, generate large amounts of molecular data, holding a wealth of knowledge. These datasets unveil the roles of genes and their interactions with various factors through analysis, shedding light on previously unknown molecular mechanisms underlying disease pathogenesis. Furthermore, they facilitate the discovery of biomarkers crucial for …

Isolation Of Gametophytic Selection And Selective Embryo Abortion In Mimulus Guttatus, Desmond C. Willson

University Honors Theses

A lack of genomic studies examining gametophytic selection (GS) and selective embryo abortion (SEA)--which occur during the reproduction of angiosperms--leaves questions regarding the adaptive and evolutionary effects of these processes. Analyzing deviations from Mendelian segregation offers an avenue for identifying loci targeted by GS and SEA, and their contributions to purging of genetic load. However, other selective processes such as meiotic drive and cytonuclear interactions, as well as pollen and ovule abortion, can cause distortion. To distinguish the effects of GS and SEA from other causes of distortion, we will perform reciprocal crosses between highly homozygous and highly heterozygous individuals …

Improving Access To Exome Sequencing In A Medically Underserved Population Through The Texome Project, Blake Vuocolo, Ryan J German, Seema R Lalani, Chaya N Murali, Carlos A Bacino, Stephanie Baskin, Rebecca Littlejohn, John D Odom, Scott Mclean, Carrie Schmid, Morgan Nutter, Melissa Stuebben, Emily Magness, Olivia Juarez, Dina El Achi, Bailey Mitchell, Kevin E Glinton, Laurie Robak, Sandesh C S Nagamani, Lisa Saba, Adasia Ritenour, Lilei Zhang, Haley Streff, Katie Chan, K Jordan Kemere, Kent Carter, Texome Project, Nichole Owen, Liesbeth Vossaert, Pengfei Liu, Hugo Bellen, Michael F Wangler

Faculty, Staff and Students Publications

PURPOSE: Genomic medicine can end diagnostic odysseys for patients with complex phenotypes; however, limitations in insurance coverage and other systemic barriers preclude individuals from accessing comprehensive genetics evaluation and testing.

METHODS: The Texome Project is a 4-year study that reduces barriers to genomic testing for individuals from underserved and underrepresented populations. Participants with undiagnosed, rare diseases who have financial barriers to obtaining exome sequencing (ES) clinically are enrolled in the Texome Project.

RESULTS: We highlight the Texome Project process and describe the outcomes of the first 60 ES results for study participants. Participants received a genetic evaluation, ES, and return …

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Crossing The Ocean: The Importance Of Gene Flow In Island Evolution, Ethan F. Gyllenhaal

Biology ETDs

Islands have long been a critical arena for the development of ecological and evolutionary theory, particular due to persistent open-water gaps between them. In this dissertation I demonstrates how these caps are permeable, which can be leveraged to understand evolution on islands and more broadly. The first chapter develops this connection between ongoing, overwater gene flow and island biogeographic theory, and tests it on an archipelago species. The second take a three-pronged approach in demonstrating how over-water gene flow can bias phylogenetic inference, and how many phylogeographic metrics in islands are likely shaped by long-term gene flow. The final two …

Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou

Theses & Dissertations

Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …

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 …

Exploring Genomic Convergence For Adaptations To Freezing Environments In Polar Fish, Ethan Talley

Biological Sciences Undergraduate Honors Theses

Convergent evolution provides valuable insights into how natural selection shapes species traits. Genomic analysis of lineages that display convergent traits has the potential to identify candidate genes for environmental adaptations across the scope of entire genomes. One remarkable example of convergent evolution is the independent development of antifreeze proteins (AFPs) in phylogenetically distant polar fish lineages. While AFPs themselves are relatively well studied, the full genomic context of adaptation to freezing conditions in these fish lineages remains largely unexplored. Leveraging the whole genome sequences previously assembled in our lab, along with other high-quality genomes available in GenBank, I examined the …

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 …

Understanding The Origin Of Parthenogenesis Via Crossing And Crispr Gene Editing In Daphnia Pulex, Thinh Pham

Biology Dissertations - Archive

Daphnia has been used as a key model system for studying ecological changes, evolution, and genomics for the past few decades due to its rapid turnover time in reproduction. The organism possesses two fascinating modes of reproduction: obligate parthenogenesis and cyclical parthenogenesis. This dissertation delves into the intricate reproductive strategies of Daphnia pulex, focusing on hybrid F1s from different reproductive modes. The first aim is to investigate 31 hybrid F1s generated from obligate parthenogenesis (OP) and cyclical parthenogenesis (CP) parental lines. Transcriptomic analysis reveals misexpression patterns and regulatory divergences, highlighting meiosis-related genes like CDC6 as potential parthenogenesis regulators. The …

The Influence Of Drd2 Polymorphism Exon 8 C/T (Rs6276) On Manifestations Of Delirium Tremens & Alcohol Withdrawal Seizures, Naomi Schneider

Honors Theses and Capstones

This study explores the correlation between the DRD2 Polymorphism exon 8 C/T (rs6276) and manifestations of delirium tremens (DT). DT is a condition that is clinically diagnosed utilizing two characteristic symptom manifestations: the presence of delirium and severe alcohol withdrawal. It is not entirely understood why DT can occur in some patients, but evidence has suggested that genetic predisposition can play a role. Utilizing the National Institutes of Health (NIH) All of Us Research database and performing a secondary analysis of existing genomic data, this candidate gene association study aims to determine the genotype frequencies within three cohorts: a healthy …

Personalized Molecular Therapies For Advanced Non-Small Cell Lung Cancer: Overcoming Heterogeneity To Optimize Treatment Response And Clinical Outcomes, Zuan-Fu Lim

Graduate Theses, Dissertations, and Problem Reports (ETD)

Lung cancer remains one of the deadliest cancers. Novel, paradigm shifting treatments including immunotherapy and targeted therapies have recently been developed to cull the deadly effects of lung cancer, but many challenges remain. There remains a significant unmet need to accurately predict and optimally select for patients who will respond to immune checkpoint inhibitors (ICI) treatment. In Chapter 2 of this dissertation, we investigated a novel live single cell cytokine profiling lab-on-chip platform, IsoLight, using peripheral CD4+ and CD8+ T-cells for ICI biomarker development. A total of 55,175 single T-lymphocytes were analyzed in this proof-of-concept study. We found that an …

The Influence Of Genes On The Migratory Timing Of Great Reed Warblers, Emily Fackler

Honors Undergraduate Theses

Many organisms migrate; however, there is a lack of knowledge on the mechanisms that drive migration timing, including which genes play a role. The great reed warbler (Acrocephalus arundinaceus), a migratory bird that breeds in Eurasia and overwinters in sub-Saharan Africa, is an excellent model to study the genetics of migration. Each season, some individuals migrate early, whereas others migrate later in the season. In other words, they exhibit differences in their migratory chronotypes. Past research has identified three candidate genes (TOP1, PEAK1, and CPNE4) that influence the migratory chronotypes of another avian species, …

Investigating The Impact Of Transcription On Mutation Rates, Sarah Patterson

Theses and Dissertations

tRNA genes are highly transcribed and perform one of the most fundamental cellular functions. Although a universal pattern observed across all three domains of life is that highly transcribed genes tend to evolve slowly, tRNA genes have been shown previously to evolve rapidly. This rapid sequence evolution could result from relaxed selection, increased mutation rate, or a combination of both. Here, we use mutation-accumulation line sequencing data to show that tRNA genes accumulate more mutations than other gene types. Our results indicate that this elevated mutation rate is a consequence of both elevated transcription-associated mutagenesis and a lack of transcription-coupled …

The Detection Of Putative Recessive Lethal Haplotypes In Irish Sheep Populations, Rory Mcauley

ORBioM (Open Research BioSciences Meeting)

In livestock populations, recessive lethal alleles are a known contributor to poor reproductive performance due to embryonic death in homozygous individuals. Despite their lethal effect in the recessive form, these alleles may be maintained at high frequencies among carrier animals because of their positive pleiotropic effects on economically important traits. Although several such recessive alleles have been identified in cattle and pig populations, limited studies have been completed in sheep, and none within Irish sheep populations. Genotype data for 69,034 animals from five major Irish sheep breeds genotyped on a variety of panels was available for this study. Only animals …

Collagene Enables Privacy-Aware Federated And Collaborative Genomic Data Analysis, Wentao Li, Miran Kim, Kai Zhang, Han Chen, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

Growing regulatory requirements set barriers around genetic data sharing and collaborations. Moreover, existing privacy-aware paradigms are challenging to deploy in collaborative settings. We present COLLAGENE, a tool base for building secure collaborative genomic data analysis methods. COLLAGENE protects data using shared-key homomorphic encryption and combines encryption with multiparty strategies for efficient privacy-aware collaborative method development. COLLAGENE provides ready-to-run tools for encryption/decryption, matrix processing, and network transfers, which can be immediately integrated into existing pipelines. We demonstrate the usage of COLLAGENE by building a practical federated GWAS protocol for binary phenotypes and a secure meta-analysis protocol. COLLAGENE is available at https://zenodo.org/record/8125935 …

Characterization Of The Immunoglobulin Lambda Chain Across Diverse Human Populations., William Gibson

Electronic Theses and Dissertations

The adaptive immune system relies on a diverse set of over one hundred immunoglobulin (IG) genes across three genomic loci that are variably combined to form antibodies (Ab). The IG Lambda locus is one of two loci which encodes the IG light chain. The complexity of the IGL locus severely limits the effective use of standard short-read sequencing, limiting our knowledge of population diversity in these loci. We leveraged single molecule real-time (SMRT) long-read sequencing in conjunction with IGL-targeted DNA capture to develop the method IG-Cap for accurate and high-throughput sequencing of the IGL locus. We benchmarked this method using …