Bioinformatics Commons^™

Computational Molecular Coevolution, Russell J. Dickson

Electronic Thesis and Dissertation Repository

A major goal in computational biochemistry is to obtain three-dimensional structure information from protein sequence. Coevolution represents a biological mechanism through which structural information can be obtained from a family of protein sequences. Evolutionary relationships within a family of protein sequences are revealed through sequence alignment. Statistical analyses of these sequence alignments reveals positions in the protein family that covary, and thus appear to be dependent on one another throughout the evolution of the protein family. These covarying positions are inferred to be coevolving via one of two biological mechanisms, both of which imply that coevolution is facilitated by inter-residue …

Characterizing The Human Vaginal Microbiome Using High-Throughput Sequencing, Jean Megan E. Macklaim

Electronic Thesis and Dissertation Repository

The human vaginal microbiome undoubtedly has a significant role in reproductive health and for protection from infectious organisms. Recent efforts to characterize the bacterial species of the vagina using molecular techniques have uncovered an unexpected diversity. Using high-throughput sequencing I sought to describe the structure and function of the vaginal microbiome under different physiological states including healthy, bacterial vaginosis (BV), post-menopausal vaginal atrophy, and acute vulvovaginal candidiasis (VVC).

Partial 16S rRNA gene sequencing revealed that healthy, asymptomatic women most often have vaginal biotas dominated by Lactobacillus iners or L. crispatus. In contrast, BV is a heterogeneous, highly diversified condition …

Role Of Branched-Chain Amino Acid Transporters In Staphylococcus Aureus Virulence, Sameha Omer

Electronic Thesis and Dissertation Repository

Branched-chain amino acids (BCAAs) act as effector molecules that signal a global transcriptional regulator, CodY, to regulate virulence factors in nutrient depleted environments. Staphylococcus aureus contains three putative BCAA transporters (BrnQ1, BrnQ2, BrnQ3) whose role in BCAA uptake is unknown. We hypothesize that BrnQ transporters are involved in BCAA uptake and contribute to virulence in S. aureus by modulating CodY activity. Results from radioactive uptake assays indicate that BrnQ1 is the predominant BrnQ transporter of isoleucine, valine and leucine. Meanwhile, BrnQ2 is more specific for isoleucine. Furthermore, only the lack of BrnQ1 hinders growth of S. aureus in chemically-defined media …

Modeling Leafhopper Populations And Their Role In Transmitting Plant Diseases., Ji Ruan

Electronic Thesis and Dissertation Repository

This M.Sc. thesis focuses on the interactions between crops and leafhoppers.

Firstly, a general delay differential equations system is proposed, based on the infection age structure, to investigate disease dynamics when disease latencies are considered. To further the understanding on the subject, a specific model is then introduced. The basic reproduction numbers $\cR_0$ and $\cR_1$ are identified and their threshold properties are discussed. When $\cR_0 < 1$, the insect-free equilibrium is globally asymptotically stable. When $\cR_0 > 1$ and $\cR_1 < 1$, the disease-free equilibrium exists and is locally asymptotically stable. When $\cR_1>1$, the disease will persist.

Secondly, we derive another general delay differential equations system to examine how different life stages of leafhoppers affect crops. The basic reproduction numbers $\cR_0$ is determined: when …

Array-Based Genomic Diversity Measures Portray Mus Musculus Phylogenetic And Genealogical Relationships, And Detect Genetic Variation Among C57bl/6j Mice And Between Tissues Of The Same Mouse, Susan T. Eitutis

Electronic Thesis and Dissertation Repository

Mouse models lack affordable genomic technologies slowing the identification of candidate variants contributing to complex phenotypes. The Mouse Diversity Genotyping Array (MDGA) is a low cost, high-resolution platform permitting genomic diversity assessment. Using a validated list of >500,000 single nucleotide polymorphisms (SNPs), we applied the first comprehensive analysis of SNP differences to detect genetic distance across 362 Mus musculus samples. Genetic distance measured between distantly and closely related mice correlates with known phylogeny and genealogy. Variation detected between C57BL/6J mice is consistent with previous reports of variants within this strain. Putative genetic variation detected between and within tissues indicates somatic …

Identification Of Cyclophilin Gene Family In Soybean And Characterization Of Gmcyp1, Hemanta Raj Mainali

Electronic Thesis and Dissertation Repository

I identified members of the Cyclophilin (CYP) gene family in soybean (Glycine max) and characterized the GmCYP1, one of the members of soybean CYP. CYPs belong to the immunophilin superfamily with peptidyl-prolyl cis-trans isomerase (PPIase) activity. PPIase catalyzes the interconversion of the cis- and trans-rotamers of the peptidyl-prolyl amide bond of peptides. After extensive data mining, I identified 62 different CYP genes in soybean (GmCYP1 to GmCYP62), of which 8 are multi-domain proteins and 54 are single domain proteins. At least 25% of the GmCYP genes are expressed in soybean. GmCYP1 …

Genetic Approaches To Studying Complex Human Disease, Joseph B. Dube

Electronic Thesis and Dissertation Repository

Common, complex diseases such as cardiovascular disease (CVD) represent an intricate interaction between environmental and genetic factors and now account for the leading causes of mortality in western society. By investigating the genetic component of complex disease etiology, we have gained a better understanding of the biological pathways underlying complex disease and the heterogeneity of complex disease risk. However, the development of high throughput genomic technologies and large well-phenotyped multi-ethnic cohorts has opened the door towards more in-depth and trans-disciplinary approaches to studying the genetics of complex disease pathogenesis. Accordingly, we sought to investigate select complex traits and diseases using …

A Quantitative Method For Measuring And Visualizing Species' Relatedness In A Two-Dimensional Euclidean Space., Abu Sadat Md. Sayem

Electronic Thesis and Dissertation Repository

Representing DNA sequences graphically and evaluating, as well as displaying, species’ relationships have been considered to be an important aspect of molecular biology research. A novel approach is proposed in this thesis that combines three methods: a) Chaos Game Representation (CGR), to portray quantitative characteristics of a DNA sequence as a black-and -white image, b) Structural Similarity (SSIM) index, an image comparison method, to compute pair-wise distances between these images, and c) Multidimensional Scaling (MDS), to visually display each sequence as a point in a two-dimensional Euclidean space. The proposed method produces a visual representation called Genome Distance Map (GDM) …

Interpretation, Stratification And Validation Of Sequence Variants Affecting Mrna Splicing In Complete Human Genome Sequences, Ben C. Shirley

Electronic Thesis and Dissertation Repository

The Shannon Human Splicing Pipeline software has been developed to analyze variants on a genome-scale. Evidence is provided that this software predicts variants affecting mRNA splicing. Variants are examined through information-based analysis and the context of novel mutations as well as common and rare SNPs with splicing effects are displayed. Potential natural and cryptic mRNA splicing variants are identified, and inactivating mutations are distinguished from leaky mutations. Mutations and rare SNPs were predicted in genomes of three cancer cell lines (U2OS, U251 and A431), supported by expression analyses. After filtering, tractable numbers of potentially deleterious variants are predicted by the …