Bioinformatics Commons^™

Insights To Protein Pathogenicity From The Lens Of Protein Evolution, Janelle Nunez-Castilla

FIU Electronic Theses and Dissertations

As protein sequences evolve, differences in selective constraints may lead to outcomes ranging from sequence conservation to structural and functional divergence. Evolutionary protein family analysis can illuminate which protein regions are likely to diverge or remain conserved in sequence, structure, and function. Moreover, nonsynonymous mutations in pathogens may result in the emergence of protein regions that affect the behavior of pathogenic proteins within a host and host response. I aimed to gain insight on pathogenic proteins from cancer and viruses using an evolutionary perspective. First, I examined p53, a conformationally flexible, multifunctional protein mutated in ~50% of human cancers. Multifunctional …

In Silico Characterization Of Protein-Protein Interactions Mediated By Short Linear Motifs, Heidy Elkhaligy

FIU Electronic Theses and Dissertations

Short linear motifs (SLiMs), often found in intrinsically disordered regions (IDPs), can initiate protein-protein interactions in eukaryotes. Although pathogens tend to have less disorder than eukaryotes, their proteins alter host cellular function through molecular mimicry of SLiMs. The first objective was to study sequence-based structure properties of viral SLiMs in the ELM database and the conservation of selected viral motifs involved in the virus life cycle. The second objective was to compare the structural features for SliMs in pathogens and eukaryotes in the ELM database. Our analysis showed that many viral SliMs are not found in IDPs, particularly glycosylation motifs. …

A Machine Learning Framework For Identifying Molecular Biomarkers From Transcriptomic Cancer Data, Md Abdullah Al Mamun

FIU Electronic Theses and Dissertations

Cancer is a complex molecular process due to abnormal changes in the genome, such as mutation and copy number variation, and epigenetic aberrations such as dysregulations of long non-coding RNA (lncRNA). These abnormal changes are reflected in transcriptome by turning oncogenes on and tumor suppressor genes off, which are considered cancer biomarkers.

However, transcriptomic data is high dimensional, and finding the best subset of genes (features) related to causing cancer is computationally challenging and expensive. Thus, developing a feature selection framework to discover molecular biomarkers for cancer is critical.

Traditional approaches for biomarker discovery calculate the fold change for each …

Taxonomy And Systematics Of Plumeria L. (Apocynaceae) In The Caribbean Islands, Nichole M. Tiernan

FIU Electronic Theses and Dissertations

Plumeria L. (Apocynaceae) is a genus of flowering trees and shrubs that are often cultivated in tropical gardens worldwide. The majority of its species occur in the Greater Antilles with many as single-island endemics. The only comprehensive revision for the genus was done by Robert E. Woodson Jr. (1937) who recognized only seven species and created a ‘Plumeria obtusa complex’ with a plethora of synonyms. The first study provides an overview of the Caribbean Island members of the genus with a focus on Plumeria filifolia Griseb., a thin-leaved species endemic to Cuba that is featured because of its incredible …

Connections In The Underworld: A Morphological And Molecular Study Of Diversity And Connectivity Among Anchialine Shrimp., Robert Eugene Ditter

FIU Electronic Theses and Dissertations

This research investigates the distribution and population structure of crustaceans, endemic to anchialine systems in the tropical western Atlantic focusing on cave-dwelling shrimp from the family Barbouriidae. Taxonomic and molecular tools (genetic and genomic) are utilized to examine population dynamics and the presence of phenotypic hypervariation (PhyV) of the critically endangered species Barbouria cubensis (von Martens, 1872). The presence of PhyV and its geographic distribution is investigated among anchialine populations of B. cubensis from 34 sites on Abaco, Eleuthera, and San Salvador, Bahamas. Examination of 54 informative morphological characters revealed PhyV present in nearly 90% (n=463) of specimens with no …

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 …

Computational Analysis Of Large-Scale Trends And Dynamics In Eukaryotic Protein Family Evolution, Joseph Boehm Ahrens

FIU Electronic Theses and Dissertations

The myriad protein-coding genes found in present-day eukaryotes arose from a combination of speciation and gene duplication events, spanning more than one billion years of evolution. Notably, as these proteins evolved, the individual residues at each site in their amino acid sequences were replaced at markedly different rates. The relationship between protein structure, protein function, and site-specific rates of amino acid replacement is a topic of ongoing research. Additionally, there is much interest in the different evolutionary constraints imposed on sequences related by speciation (orthologs) versus sequences related by gene duplication (paralogs). A principal aim of this dissertation is to …

The Role Of Id3 And Pcb153 In The Hyperproliferation And Dysregulation Of Lung Endothelial Cells, Mayur Arvind Doke

FIU Electronic Theses and Dissertations

Uncontrolled growth of vascular stem cells as a result of endothelial-mesenchymal transition is considered to cause hyper-proliferative vascular remodeling in severe pulmonary arterial hypertension (PAH) patients. Hyperplastic intimal growth is one of the causes of closure of the lumen of pulmonary arterioles. This abnormal vessel remodeling leads to the progressive increase in pressure of the pulmonary arterioles causing severe PAH; and debilitating harm to patients resulting in mortality from right heart failure. Environmental factors, including polychlorinated biphenyls (PCBs), are considered to be involved in hyper-proliferative vascular remodeling because genetic makeup can only explain about 10% of severe PAH cases. PCB …

Exposure To Estrogenic Endocrine Disrupting Chemicals And Brain Health, Mark Preciados

FIU Electronic Theses and Dissertations

The overall objective of this dissertation was to examine exposures to the estrogenic endocrine disrupting chemicals (EEDCs), phthalates, bisphenol-A (BPA), and the metalloestrogens cadmium (Cd), arsenic (As), and manganese (Mn) in an older geriatric aged-population and examine associations with brain health. Given the evidence that EEDCs affect brain health and play a role in the development of cognitive dysfunction and neurodegenerative disease, and the constant environmental exposure through foods and everyday products has led this to becoming a great public health concern. Using a bioinformatic approach to find nuclear respiratory factor 1 (NRF1) gene targets involved in mitochondrial dysfunction, that …

Transcriptomic And Epigenetic Responses To Environmental Stress In Marine Bivalves With A Focus On Harmful Algal Blooms, Maria Victoria Suarez Ulloa

FIU Electronic Theses and Dissertations

Global change poses new threats for life in the oceans forcing marine organisms to respond through molecular acclimatory and adaptive strategies. Although bivalve molluscs are particularly tolerant and resilient to environmental stress, they must now face the challenge of more frequent and severe Harmful Algal Blooms (HABs) episodes. These massive outbreaks of microalgae produce toxins that accumulate in the tissues of these filter-feeder organisms, causing changes in their gene expression profiles, which in turn modify their phenotype in order to maintain homeostasis. Such modifications in gene expression are modulated by epigenetic mechanisms elicited by specific environmental stimuli, laying the foundations …

Employing Limited Next Generation Sequence Data For The Development Of Genetic Loci Of Phylogenetic And Population Genetic Utility, Lauren Evenstone

FIU Electronic Theses and Dissertations

Massively parallel high throughput sequencers are transforming the scientific research by reducing the cost and time necessary to sequence entire genomes. The goal of this project is to produce preliminary genome assemblies of calliphorid flies using Life Technologies’ Ion Torrent sequencing and Illumina’s MiSeq sequencing. I located, assembled, and annotated a novel mitochondrial genome for one such fly, the little studied Chrysomya pacifica that is central to one hypothesis about blow fly evolution. With sequencing data from Chrysomya megacephala, its forensically relevant sister species, much insight can be gained by alignments, sequence and protein analysis, and many more tools …

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA …

Pseudomonas Aeruginosa Ampr Transcriptional Regulatory Network, Deepak Balasubramanian

FIU Electronic Theses and Dissertations

In Enterobacteriaceae, the transcriptional regulator AmpR, a member of the LysR family, regulates the expression of a chromosomal β-lactamase AmpC. The regulatory repertoire of AmpR is broader in Pseudomonas aeruginosa, an opportunistic pathogen responsible for numerous acute and chronic infections including cystic fibrosis. Previous studies showed that in addition to regulating ampC, P. aeruginosa AmpR regulates the sigma factor AlgT/U and production of some quorum sensing (QS)-regulated virulence factors. In order to better understand the ampR regulon, the transcriptional profiles generated using DNA microarrays and RNA-Seq of the prototypic P. aeruginosa PAO1 strain with its isogenic ampR deletion …