Life Sciences Commons^™

On The Origin Of Phenotypic Variation: Novel Technologies To Dissect Molecular Determinants Of Phenotype, Francesco Vallania

All Theses and Dissertations (ETDs)

This thesis describes the conception, design, and development of novel computational tools, theoretical models, and experimental techniques applied to the dissection of molecular factors underlying phenotypic variation. The first part of my work is focused on finding rare genetic variants in pooled DNA samples, leading to the development of a novel set of algorithms, SNPseeker and SPLINTER, applied to next-generation sequencing data. The second part of my work describes the creation of a reporter system for DNA methylation for the purpose of dissecting the genetic contribution of tissue-specific patterns of DNA methylation across the genome. Finally the last part of …

Integrating Human Omics Data To Prioritize Candidate Genes., Yong Chen, Xuebing Wu, Rui Jiang

Faculty Scholarship for the College of Science & Mathematics

BACKGROUND: The identification of genes involved in human complex diseases remains a great challenge in computational systems biology. Although methods have been developed to use disease phenotypic similarities with a protein-protein interaction network for the prioritization of candidate genes, other valuable omics data sources have been largely overlooked in these methods.

METHODS: With this understanding, we proposed a method called BRIDGE to prioritize candidate genes by integrating disease phenotypic similarities with such omics data as protein-protein interactions, gene sequence similarities, gene expression patterns, gene ontology annotations, and gene pathway memberships. BRIDGE utilizes a multiple regression model with lasso penalty to …

Pathoscope: Species Identification And Strain Attribution With Unassembled Sequencing Data., Owen E Francis, Matthew Bendall, Solaiappan Manimaran, Changjin Hong, Nathan L Clement, Eduardo Castro-Nallar, Quinn Snell, G Bruce Schaalje, Mark J Clement, Keith A Crandall, W Evan Johnson

Computational Biology Institute

Emerging next-generation sequencing technologies have revolutionized the collection of genomic data for applications in bioforensics, biosurveillance, and for use in clinical settings. However, to make the most of these new data, new methodology needs to be developed that can accommodate large volumes of genetic data in a computationally efficient manner. We present a statistical framework to analyze raw next-generation sequence reads from purified or mixed environmental or targeted infected tissue samples for rapid species identification and strain attribution against a robust database of known biological agents. Our method, Pathoscope, capitalizes on a Bayesian statistical framework that accommodates information on sequence …

Resolving The Genetic Etiology Of Hypercholesterolemia In Familial Combined Hyperlipidemia, Mary A. Bamimore

Electronic Thesis and Dissertation Repository

Hypercholesterolemia is a classical risk factor for cardiovascular disease development. The genetic etiology of hypercholesterolemia in familial combined hyperlipidemia (FCH), one of the most common genetic dyslipidemias, is poorly understood. We aimed at understanding the genetic etiology of hypercholesterolemia in FCH.

Sequencing, genotyping and computational analyses were performed in a case-control setting to better understand the ‘nature’ aspect of hypercholesterolemia in FCH. My findings suggest that FCH more likely has a polygenic basis.

All my findings have shown that the genetic definition of a disease, especially relatively common diseases like FCH that have been previously considered to be monogenic, may …

Phage Cluster Relationships Identified Through Single Gene Analysis., Kyle C Smith, Eduardo Castro-Nallar, Joshua Nb Fisher, Donald P Breakwell, Julianne H Grose, Sandra H Burnett

Computational Biology Institute

BACKGROUND: Phylogenetic comparison of bacteriophages requires whole genome approaches such as dotplot analysis, genome pairwise maps, and gene content analysis. Currently mycobacteriophages, a highly studied phage group, are categorized into related clusters based on the comparative analysis of whole genome sequences. With the recent explosion of phage isolation, a simple method for phage cluster prediction would facilitate analysis of crude or complex samples without whole genome isolation and sequencing. The hypothesis of this study was that mycobacteriophage-cluster prediction is possible using comparison of a single, ubiquitous, semi-conserved gene. Tape Measure Protein (TMP) was selected to test the hypothesis because it …

Engaging Students In A Bioinformatics Activity To Introduce Gene Structure And Function, Barbara J. May

Biology Faculty Publications

Bioinformatics spans many fields of biological research and plays a vital role in mining and analyzing data. Therefore, there is an ever-increasing need for students to understand not only what can be learned from this data, but also how to use basic bioinformatics tools. This activity is designed to provide secondary and undergraduate biology students to a hands-on activity meant to explore and understand gene structure with the use of basic bioinformatic tools. Students are provided an “unknown” sequence from which they are asked to use a free online gene finder program to identify the gene. Students then predict the …

A Comparative Genomics Approach To Using High-Throughput Gene Expression Data To Study Limb Regeneration In Ambystoma Mexicanum And Danio Rerio: Developing A More Completely Annotated Database, Justin Bolinger

Honors College

Axolotl (Ambystoma mexicanum) and the zebrafish (Danio rerio) represent organisms extensively studied because of their remarkable capability of fully regenerating completely functional tissues after a traumatic event takes place. However, the research conducted with regards to the genomics of these two organisms has remained fairly independent of each other. The intent of this study is to bridge this gap and connect genes between axolotl and the zebrafish by use a “Rosetta stone” framework to develop a database comparing gene expression data obtained from both microarraybased experiments and high-throughput DNA sequencing of axolotl and zebrafish mRNA and miRNA. Using gene data …

Tracing Evolutionary Footprints To Identify Novel Gene Functional Linkages., Yong Chen, Li Yang, Yunfeng Ding, Shuyan Zhang, Tong He, Fenglou Mao, Congyan Zhang, Huina Zhang, Chaoxing Huo, Pingsheng Liu

Faculty Scholarship for the College of Science & Mathematics

Systematic determination of gene function is an essential step in fully understanding the precise contribution of each gene for the proper execution of molecular functions in the cell. Gene functional linkage is defined as to describe the relationship of a group of genes with similar functions. With thousands of genomes sequenced, there arises a great opportunity to utilize gene evolutionary information to identify gene functional linkages. To this end, we established a computational method (called TRACE) to trace gene footprints through a gene functional network constructed from 341 prokaryotic genomes. TRACE performance was validated and successfully tested to predict enzyme …

Bayesian Methods For Expression-Based Integration, Elizabeth M. Jennings, Jeffrey S. Morris, Raymond J. Carroll, Ganiraju C. Manyam, Veera Baladandayuthapani

Jeffrey S. Morris

We propose methods to integrate data across several genomic platforms using a hierarchical Bayesian analysis framework that incorporates the biological relationships among the platforms to identify genes whose expression is related to clinical outcomes in cancer. This integrated approach combines information across all platforms, leading to increased statistical power in finding these predictive genes, and further provides mechanistic information about the manner in which the gene affects the outcome. We demonstrate the advantages of the shrinkage estimation used by this approach through a simulation, and finally, we apply our method to a Glioblastoma Multiforme dataset and identify several genes potentially …