Life Sciences Commons^™

Physiologic And Pathologic Profiling Of Clonal Variations, Wing Hing Wong

Arts & Sciences Electronic Theses and Dissertations

This thesis sought to provide a better understanding of clonality in various malignant and non-malignant settings using a variety of genomic analytical tools. Clonality is pre-defined as the presence of a mixed population of cells in which each sub-population has distinct somatic mutation profile. It is a common feature in cancers where subpopulations of cells arise as a result of independent, yet continual acquisition of somatic mutations. The clonal architecture of cancers can be used as a diagnostic and prognostic biomarker as well as to monitor disease progression or resolution. Besides cancer, clonal variability and expansion is also implicated in …

Promises And Challenges Of Eco-Physiological Genomics In The Field: Tests Of Drought Responses In Switchgrass. Plant Physiology, John T. Lovell, Eugene V. Shakirov, Scott Schwartz, David B. Lowry, Michael J. Aspinwall, Samuel H. Taylor, Jason Bonnette, Juan Diego Palacio-Mejia, Christine V. Hawkes, Philip A. Fay, Thomas E. Juenger

Yevgeniy (Eugene) Shakirov

Identifying the physiological and genetic basis of stress tolerance in plants has proven to be critical to understanding adaptation in both agricultural and natural systems. However, many discoveries were initially made in the controlled conditions of greenhouses or laboratories, not in the field. To test the comparability of drought responses across field and greenhouse environments, we undertook three independent experiments using the switchgrass reference genotype Alamo AP13. We analyzed physiological and gene expression variation across four locations, two sampling times, and three years. Relatively similar physiological responses and expression coefficients of variation across experiments masked highly dissimilar gene expression responses …

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

Yong Chen

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 …

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

Yong Chen

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 …

Integrated Omics Study Delineates The Dynamics Of Lipid Droplets In Rhodococcus Opacus Pd630., Yong Chen, Yunfeng Ding, Li Yang, Jinhai Yu, Guiming Liu, Xumin Wang, Shuyan Zhang, Dan Yu, Lai Song, Hangxiao Zhang, Congyan Zhang, Linhe Huo, Chaoxing Huo, Yang Wang, Yalan Du, Huina Zhang, Peng Zhang, Huimin Na, Shimeng Xu, Yaxin Zhu, Zhensheng Xie, Tong He, Yue Zhang, Guoliang Wang, Zhonghua Fan, Fuquan Yang, Honglei Liu, Xiaowo Wang, Xuegong Zhang, Michael Q Zhang, Yanda Li, Alexander Steinbüchel, Toyoshi Fujimoto, Simon Cichello, Jun Yu, Pingsheng Liu

Yong Chen

Rhodococcus opacus strain PD630 (R. opacus PD630), is an oleaginous bacterium, and also is one of few prokaryotic organisms that contain lipid droplets (LDs). LD is an important organelle for lipid storage but also intercellular communication regarding energy metabolism, and yet is a poorly understood cellular organelle. To understand the dynamics of LD using a simple model organism, we conducted a series of comprehensive omics studies of R. opacus PD630 including complete genome, transcriptome and proteome analysis. The genome of R. opacus PD630 encodes 8947 genes that are significantly enriched in the lipid transport, synthesis and metabolic, indicating a super …

Rare Degs1 Variant Significantly Alters De Novo Ceramide Synthesis Pathway, Nicholas B. Blackburn, Laura F. Michael, Peter J. Meikle, Juan M. Peralta, Marian Mosior, Scott Mcahren, Hai H. Bui, Melissa A. Bellinger, Corey Giles, Satish Kumar, Ana C. Leandro, Marcio Almeida, Jacquelyn M. Weir, Michael C. Mahaney, Thomas D. Dyer, Laura Almasy, John L. Vandeberg, Sarah Williams-Blangero, David C. Glahn, Ravindranath Duggirala, Mark Kowala, John Blangero, Joanne E. Curran

School of Medicine Publications and Presentations

The de novo ceramide synthesis pathway is essential to human biology and health but genetic influences remain unexplored. The core function of this pathway is the generation of biologically active ceramide from its precursor, dihydroceramide. Dihydroceramides have diverse, often protective, biological roles; conversely, increased ceramide levels are biomarkers of complex disease. To explore the genetics of the ceramide synthesis pathway, we searched for deleterious nonsynonymous variants in the genomes of 1,020 Mexican Americans from extended pedigrees. We identified a Hispanic ancestry−specific rare functional variant, L175Q, in DEGS1, a key enzyme in the pathway that converts dihydroceramide to ceramide. This amino …

Validity Evaluation Of The Genetics And Genomics In Nursing Practice Survey, Alexandra Plavskin, William E. Samuels, Kathleen A. Calzone

Publications and Research

Aim: To psychometrically test the Genetics and Genomics Nursing Practice Survey (GGNPS) for evidence of content, face and construct validity.

Design:This study was a secondary data analysis.

Method: Data collected from the Method for Introducing a New Competency into Nursing Practice (MINC) study were used to evaluate the GGNPS for evidence of construct validity via structural equation modelling and confirmatory factor analysis. Face validity was evaluated via feedback from practicing RNs without specific experience with or knowledge of genetics/genomics. Content validity was evaluated via content expert feedback and assessment of a content validity index.

Results: The thresholds …

Mixing It Up: The Impact Of Episodic Introgression On The Evolution Of High-Latitude Mesocarnivores, Jocelyn P. Colella

Biology ETDs

At high latitudes, climatic oscillations have triggered repeated episodes of organismal divergence by geographically isolating populations. For terrestrial species, extended isolation in glacial refugia – ice-free regions that enable terrestrial species persistence through glacial maxima – is hypothesized to stimulate allopatric divergence. Alternatively, upon glacial recession, divergent populations expanded from independent glacial refugia and often contacted other diverging populations. In the absence of reproductive isolating mechanisms, this biogeographic process may trigger hybridization and ultimately, gene flow between divergent taxa. My dissertation research aims to understand how these episodic periods of isolation and contact have impacted the evolution of high latitude …

A Method For Improving The Accuracy And Efficiency Of Bacteriophage Genome Annotation, Alicia Salisbury, Philippos K. Tsourkas

Life Sciences Faculty Research

Bacteriophages are the most numerous entities on Earth. The number of sequenced phage genomes is approximately 8000 and increasing rapidly. Sequencing of a genome is followed by annotation, where genes, start codons, and functions are putatively identified. The mainstays of phage genome annotation are auto-annotation programs such as Glimmer and GeneMark. Due to the relatively small size of phage genomes, many groups choose to manually curate auto-annotation results to increase accuracy. An additional benefit of manual curation of auto-annotated phage genomes is that the process is amenable to be performed by students, and has been shown to improve student recruitment …

Genome Of The Tropical Plant Marchantia Inflexa: Implications For Sex Chromosome Evolution And Dehydration Tolerance, Rose A. Marks, Jeramiah J. Smith, Quentin Cronk, Christopher J. Grassa, D. Nicholas Mcletchie

Biology Faculty Publications

We present a draft genome assembly for the tropical liverwort, Marchantia inflexa, which adds to a growing body of genomic resources for bryophytes and provides an important perspective on the evolution and diversification of land plants. We specifically address questions related to sex chromosome evolution, sexual dimorphisms, and the genomic underpinnings of dehydration tolerance. This assembly leveraged the recently published genome of related liverwort, M. polymorpha, to improve scaffolding and annotation, aid in the identification of sex-linked sequences, and quantify patterns of sequence differentiation within Marchantia. We find that genes on sex chromosomes are under greater …

Differential Effects Of Influenza Virus Na, Ha Head, And Ha Stalk Antibodies On Peripheral Blood Leukocyte Gene Expression During Human Infection., Kathie-Anne Walters, Ruoqing Zhu, Michael Welge, Kelsey Scherler, Jae-Keun Park, Zainab Rahil, Hao Wang, Loretta Auvil, Colleen Bushell, Min Young Lee, David Baxter, Tyler Bristol, Luz Angela Rosas, Adriana Cervantes-Medina, Lindsay Czajkowski, Alison Han, Matthew J Memoli, Jeffery K Taubenberger, John C Kash

Articles, Abstracts, and Reports

In this study, we examined the relationships between anti-influenza virus serum antibody titers, clinical disease, and peripheral blood leukocyte (PBL) global gene expression during presymptomatic, acute, and convalescent illness in 83 participants infected with 2009 pandemic H1N1 virus in a human influenza challenge model. Using traditional statistical and logistic regression modeling approaches, profiles of differentially expressed genes that correlated with active viral shedding, predicted length of viral shedding, and predicted illness severity were identified. These analyses further demonstrated that challenge participants fell into three peripheral blood leukocyte gene expression phenotypes that significantly correlated with different clinical outcomes and prechallenge serum …

The Relationship Between Uncertainty Tolerance And Oncologists’ Perceptions Of Large-Panel Genomic Tumor Testing, Eric Anderson, Alexandra Hinton, Christine Lary, Kimberly Murray, Leo Waterson, Paul Han, Maine Cancer Genomics Initiative

Maine Medical Center

Introduction:

Large-panel genomic tumor testing (GTT) is a new technology that promises to make cancer treatment more precise, but that currently poses many uncertainties regarding its clinical value and appropriate use. Uncertainty Tolerance (UT), a psychological construct that describes trait-level differences in individuals’ responses to uncertainty, may influence oncologists’ perceptions and attitudes regarding GTT.

Community Oncology Clinicians’ Knowledge, Beliefs, And Attitudes Regarding Genomic Tumor Testing, Eric Anderson, Alexandra Hinton, Kimberly Murray, Hayley Mandeville, Caitlin Gutheil, Leo Waterston, Lee Lucas, Christine Duarte, Christian Thomas, Susan Miesfeldt, Petra Helbig, Andrey Antov, Jens Rueter, Paul Han

Maine Medical Center

Introduction: Genomic tumor testing (GTT) is a new technology that promises to make cancer treatment more precise. However, little is known about clinicians’ knowledge, beliefs, and attitudes regarding GTT, particularly in community oncology settings.

Genomics Based Approaches To Fungal Evolution, Aaron J. Robinson, Donald O. Natvig

Biology ETDs

Advances in DNA sequencing and data analysis make it possible to address questions in population genetics and evolution at the genomic level. Fungi are excellent subjects for such studies, because they are found in diverse environments, have short generation times, can be maintained in culture and have relatively small genomes. My research employed genetic approaches using a variety of sequencing technologies and methods of analysis to explore questions in fungal evolution.

In one study, I explored the genetics behind differences in thermotolerance between isolates of Neurospora discreta from Alaska and New Mexico. Isolates from the two states exhibited differences in …

Cryptic Lineages And A Population Damned To Incipient Extinction? Insights Into The Genetic Structure Of A Mekong River Catfish, Amanda S. Ackiss, Binh T. Dang, Christopher E. Bird, Ellen E. Biesack, Phen Chheng, Latsamy Phounvisouk, Quyen H.D. Vu, Sophorn Uy, Kent E. Carpenter

Biological Sciences Faculty Publications

An understanding of the genetic composition of populations across management boundaries is vital to developing successful strategies for sustaining biodiversity and food resources. This is especially important in ecosystems where habitat fragmentation has altered baseline patterns of gene flow, dividing natural populations into smaller sub-populations and increasing potential loss of genetic variation through genetic drift. River systems can be highly fragmented by dams built for flow regulation and hydropower. We used reduced-representation sequencing to examine genomic patterns in an exploited catfish, Hemibagrus spilopterus, in a hotspot of biodiversity and hydropower development- the Mekong River basin. Our results revealed the …

Shared Heritability And Functional Enrichment Across Six Solid Cancers, Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez

Markey Cancer Center Faculty Publications

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r_g = 0.57, p = 4.6 × 10⁻⁸), breast and ovarian cancer (r_g = 0.24, p = 7 × 10^{−5 …}

Population Structure And Connectivity Of A Groundwater Crustacean Across Northwestern Montana Aquifers, Megan N. Ritter

Master’s Theses

Floodplain aquifer systems are diverse and heterogenous ecosystems that serve many ecological functions, including habitat provision to a range of groundwater species. The Flathead River system of northwestern Montana is home to many floodplain aquifers of great ecological importance to the region. The basic biology, population structure, and dispersal patterns of obligate groundwater organisms that reside within the aquifers of the Flathead are still largely unknown. In this study, we investigate the population structure of one such taxon, an undescribed species of the amphipod genus Stygobromus. For our low-coverage RADseq dataset, we tested the suitability of three different analysis …

Evidence-Based Practice Self-Study Education Program For Staff Nurses On Genomics, Nancy L. Norman-Marzella

Walden Dissertations and Doctoral Studies

Nurses routinely obtain genomic data when collecting family health histories. However, they report low confidence in their knowledge and understanding of genomics and the genetically engineered medications prescribed for their patients. The purpose of this project was the development and implementation of an evidence-based online education program about genetics and genomics to increase the nurses' understanding and ability to provide competent care for their patients receiving treatments based on the science of genomics. Knowles's principles of adult learning theory guided the development and delivery of the online education project to 12 medical-surgical registered nurses employed in a hospital in the …

Intraspecific Variation In Dehydration Tolerance: Insights From The Tropical Plant Marchantia Inflexa, Rose A. Marks

Theses and Dissertations--Biology

Plants are threatened by global change, increasing variability in weather patterns, and associated abiotic stress. Consequently, there is an urgent need to enhance our ability to predict plant community dynamics, shifts in species distributions, and physiological responses to environmental challenges. By building a fundamental understanding of plant stress tolerance, it may be possibly to protect the ecological services, economic industries, and communities that depend on plants. Dehydration tolerance (DhT) is an important mechanism of water stress tolerance with promising translational applications. Here, I take advantage natural variation in DhT to gain a deeper insight into this complex trait. In addition, …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Cisco Science: Using Omics To Answer A Range Of Key Questions, Hannah Lachance

Graduate College Dissertations and Theses

Coregonines, including cisco (Coregonus artedi), kiyi (Coregonus kiyi), and bloater (Coregonus hoyi), are a focus for prey fish conservation and restoration efforts throughout the Laurentian Great Lakes. However, fundamental questions about coregonine ecology and genetics remain. For example, we know little about how the early life stages of coregonines respond to environmental change at either the genotypic or phenotypic level. We also have limited knowledge about how to identify different species at the larval stage and the genetic relationships among species, which makes the different species difficult to study at the larval stage. To increase the probability for success in …

Saccharomyces Genome Database & Uniprot Bioinformatics Analysis, Ray A. Enke

Ray Enke Ph.D.