Genomics Commons^™

Genetic And Clinical Determinants Of Racial/Ethnic Differences In Multiple Myeloma Susceptibility And Outcomes Focusing On Hispanics, Alem Belachew

Dissertations & Theses (Open Access)

Multiple Myeloma (MM) constitutes 10% of diagnosed hematologic malignancies in the US, with over 12,000 deaths recorded each year. Race/ethnicity is a well-known MM risk factor, where individuals of African descent have over 2- to 3-fold increased risk of incidence compared to those of European descent. Additionally, Hispanics are diagnosed approximately three years younger than white American counterparts, for unknown reasons. Differences in clinical phenotype are also present for MM patients by ancestry, including varying rates of common initiation mutations such as IgH translocations and TP53 mutation between patients of European and African descent. Studies have begun to interrogate the …

The Effect Of Nuclear Perturbations On The 3d Organization Of The Genome, Rosela Golloshi

Doctoral Dissertations

Cells in our body experience constant mechanical forces that influence biological functions such as growth and development. The nucleus has been implicated as a key mechanosensor and can directly influence chromatin organization and epigenetic alterations leading to gene expression changes. However, the mechanism by which such mechanical forces lead to genomic alterations and expression of mechanosensitive genes is not fully understood. The work presented in this dissertation investigates the effect of mechanical and epigenetic perturbations on the 3D genome organization. To investigate this 3D genome folding, we use Chromosome Conformation Capture followed by high throughput sequencing (Hi-C) (Chapter-1) which identifies …

3d Genome Architecture Under Stress: A Survey Of Ionizing Radiation, Progeria, And Osmotic Stress, Jacob Tyler Sanders

Doctoral Dissertations

The human nucleus contains 2 meters of DNA which is intricately folded into a three-dimensional (3D) structure. It has become increasingly clear that this 3D structure plays an important role in the expression of genes. Proper gene expression is necessary for cellular homeostasis, cell state, and response to environmental/physical perturbations. Faithful repair of damage DNA damage is necessary to prevent genomic aberrations, such as translocations, which may lead to misregulation of gene expression. Hi-C, a sequencing technique that labels proximal chromatin interactions, provides a clearer picture of how the genome is spatially organized within the nucleus. Here, we discuss the …

Population Structure Of A Federally Endangered Plant (Astragalus Jaegerianus Munz, Fabaceae) With Limited Range Using Microsatellites, Sueann Neal

Electronic Theses, Projects, and Dissertations

Studies on population genetics examine the relationship and effects of population structure, migration, gene flow and demographic history, and are therefore important in the conservation of endangered species. Astragalus jaegerianus, a critically federally endangered species found in a geographically restricted range is investigated to determine population structure and genetic variation. Previous research on A. jaegerianus focused on DNA sequence data for cpDNA and nrDNA showed no variation. Further research on A. jaegerianus utilizing AFLP’s on the whole genome indicated substantial gene diversity and population structure consistent with geographically widespread species. AFLP research is a cost-effective process to identify levels …

P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer

Dissertations & Theses (Open Access)

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations & Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

The Genome-Wide Roles Of The Lung Lineage Transcription Factor Nkx2-1 In The Regulation Of Opposing Cell Fates In Vivo, Danielle Renae Little

Dissertations & Theses (Open Access)

Lineage transcription factors mark, promote, and maintain multiple distinct cell types originating from a common progenitor. Despite their essential role, how such factors function and bind genome wide to orchestrate the epigenetic changes necessary to form and maintain these identities in vivo is unclear. One lineage transcription factor NK Homeobox 2-1 (NKX2-1) is expressed throughout the lung epithelium during development and was thought to be lost in the extraordinarily thin cell type required for gas exchange– the alveolar type 1 (AT1) cell. Complementing precise genetic knockouts with cell type-specific ChIP-seq, ATAC-seq, and scRNA-seq, our study shows that AT1 and AT2 …

Genomics Education Partnership F Element Annotation Report, Amanda Moy

Honors Projects

The Genomics Education Partnership (GEP), headquartered at the University of Alabama, is a collection of over 100 universities that provide training and resources in order to provide students experiential learning in bioinformatics and genomics. The GEP hosts numerous research projects, including the F element project. The F element project has the main focus of annotating the F element genes of the fruit fly species D. ananassae, D. bipectinata, D. kikkawai, and D. takahashii. The Muller F element is the smallest chromosome in Drosophila species. However, the four species listed above have a notably larger F element than other …

A Context-Forward In Vivo Functional Genomics Platform For Target Discovery And Establishing Vulnerability Context In Pancreatic Cancer, Johnathon Rose, Johnathon Lynn Rose

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a very poor patient prognosis (5-year survival of ≤ 7%). While transcriptional profiling has aided in the classification of this disease into at least two broader subtypes, this alone has so far been insufficient to inform on more nuanced patterns of oncogenic dependency. We hypothesized that a more comprehensive and granular characterization of PDAC disease diversity is required to establish relevant context for targeted therapy. To this end, we sought to establish an integrated platform to: i) more comprehensively characterize differential oncogenic signaling across our tumor models, and ii) establish …

Decoding The Evolutionary Response To Prostate Cancer Therapy Using Plasma Genome Sequencing, Naveen Ramesh

Dissertations & Theses (Open Access)

Investigating genome evolution in response to therapy is difficult in human tissue samples due to the difficulty in accessing metastatic tumor sites and logistical challenges of collecting longitudinal samples. To overcome these issues, we developed an unbiased whole-genome plasma DNA sequencing approach called PEGASUS that concurrently measures genomic copy number and exome mutations from archival cryostored plasma samples. This approach was applied to study longitudinal blood plasma samples from prostate cancer patients. A molecular characterization of archival plasma DNA from 233 patients and genomic profiling of 101 patients identified clinical correlations of aneuploid plasma DNA profiles with poor survival, increased …

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

Carbon Metabolism In Cave Subaerial Biofilms, Victoria E. Frazier

Masters Theses

Subaerial biofilms (SABs) grow at the interface between the atmosphere and rock surfaces in terrestrial and subterranean environments around the world. Multi-colored SABs colonizing relatively dry and nutrient-limited cave surfaces are known to contain microbes putatively involved in chemolithoautotrophic processes using inorganic carbon like carbon dioxide (CO₂) or methane (CH₄). However, the importance of CO₂ and CH₄ to SAB biomass production has not been quantified, the environmental conditions influencing biomass production and diversity have not been thoroughly evaluated, and stable carbon and nitrogen isotope compositions have yet to be determined from epigenic cave SABs. …

Whole Genome Sequencing Identified A 16 Kilobase Deletion On Eca13 Associated With Distichiasis In Friesian Horses, E. A. Hisey, H. Hermans, Z. T. Lounsberry, F. Avila, R. A. Grahn, K. E. Knickelbein, S. A. Duward-Akhurst, M. E. Mccue, Theodore S. Kalbfleisch, M. E. Lassaline, W. Back, R. R. Bellone

Veterinary Science Faculty Publications

BACKGROUND: Distichiasis, an ocular disorder in which aberrant cilia (eyelashes) grow from the opening of the Meibomian glands of the eyelid, has been reported in Friesian horses. These misplaced cilia can cause discomfort, chronic keratitis, and corneal ulceration, potentially impacting vision due to corneal fibrosis, or, if secondary infection occurs, may lead to loss of the eye. Friesian horses represent the vast majority of reported cases of equine distichiasis, and as the breed is known to be affected with inherited monogenic disorders, this condition was hypothesized to be a simply inherited Mendelian trait.

RESULTS: A genome wide association study (GWAS) …

A Primary Human T-Cell Spectral Library To Facilitate Large Scale Quantitative T-Cell Proteomics., Harshi Weerakoon, Jeremy Potriquet, Alok K Shah, Sarah Reed, Buddhika Jayakody, Charu Kapil, Mukul K Midha, Robert L Moritz, Ailin Lepletier, Jason Mulvenna, John J Miles, Michelle M Hill

Articles, Abstracts, and Reports

Data independent analysis (DIA) exemplified by sequential window acquisition of all theoretical mass spectra (SWATH-MS) provides robust quantitative proteomics data, but the lack of a public primary human T-cell spectral library is a current resource gap. Here, we report the generation of a high-quality spectral library containing data for 4,833 distinct proteins from human T-cells across genetically unrelated donors, covering ~24% proteins of the UniProt/SwissProt reviewed human proteome. SWATH-MS analysis of 18 primary T-cell samples using the new human T-cell spectral library reliably identified and quantified 2,850 proteins at 1% false discovery rate (FDR). In comparison, the larger Pan-human spectral …

Pathway-Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Jem Bagchee-Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan

Biochemistry Publications

No abstract provided.

Quantifying Structure And Variation In Complex Phylogenetic Data, Genevieve Geraldine Mount

LSU Doctoral Dissertations

Identifying the source and structure of variation in nature is crucial to understanding fundamental aspects of evolution. Despite a recent plethora of genetic and morphological data, many interesting questions about the relationships between different groups remain unresolved. My dissertation evaluates three approaches for identifying and quantifying the variation within phylogenetic datasets. Characterizing variation within datasets and across analytical methods gives insight into biologically interesting characters, unusual evolutionary processes, and areas for model improvement.

Network-based community detection approaches offer a powerful tool to describe variation in phylogenetic signal across the genome (i.e., gene tree variation). In Chapter 2, I investigate the …

A Pilot Study Comparing The Efficacy Of Lactate Dehydrogenase Levels Versus Circulating Cell-Free Micrornas In Monitoring Responses To Checkpoint Inhibitor Immunotherapy In Metastatic Melanoma Patients., Matias A Bustos, Rebecca Gross, Negin Rahimzadeh, Hunter Cole, Linh T Tran, Kevin Tran, Ling Takeshima, Stacey L Stern, Steven O'Day, Dave Hoon

Articles, Abstracts, and Reports

Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients' disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients' responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 …

Development Of A Dna Methylation Multiplex Assay For Body Fluid Identification And Age Determination, Quentin Gauthier

FIU Electronic Theses and Dissertations

For forensic laboratories, the determination of body fluid origin of samples collected at a crime scene are typically presumptive and often destructive. However, given that in certain cases the presence of DNA is not in dispute and rather where the DNA came from is of primary concern, new methodologies are needed. Epigenetic modifications, such as DNA methylation, affect gene expression in every cell of every mammal. These DNA methylation patterns typically are observed as the addition of a methyl group on the 5’ carbon of a cytosine followed by guanine (CpG). Methylation patterns have been observed to change in response …

Characterizations Of Sars-Cov-2 Mutational Profile, Spike Protein Stability And Viral Transmission, Sayantan Laha, Joyeeta Chakraborty, Shantanab Das, Soumen Kanti Manna, Sampa Biswas, Raghunath Chatterjee

ISI Best Publications

The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has the capability of gaining rapid mutations as the virus spreads. Whole-genome sequencing data offers a wide range of opportunities to study mutation dynamics. The advantage of an increasing amount of whole-genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity, and to investigate the implications of those mutations in protein stability and viral transmission. We have identified frequently mutated residues by aligning ~660 SARS-CoV-2 genomes …

Denisovan Dna In Late Pleistocene Sediments From Baishiya Karst Cave On The Tibetan Plateau, Dongju Zhang, Huan Xia, Fahu Chen, Bo Li, Viviane Slon, Ting Cheng, Ruowei Yang, Melinda A. Yang

Biology Faculty Publications

A late Middle Pleistocene mandible from Baishiya Karst Cave (BKC) on the Tibetan Plateau has been inferred to be from a Denisovan, an Asian hominin related to Neanderthals, on the basis of an amino acid substitution in its collagen. Here we describe the stratigraphy, chronology, and mitochondrial DNA extracted from the sediments in BKC. We recover Denisovan mitochondrial DNA from sediments deposited ~100 thousand and ~60 thousand years ago (ka) and possibly as recently as ~45 ka. The long-term occupation of BKC by Denisovans suggests that they may have adapted to life at high altitudes and may have contributed such …