Genomics Commons^™

Multiple Rsv Strains Infecting Hep-2 And A549 Cells Reveal Cell Line-Dependent Differences In Resistance To Rsv Infection, Anubama Rajan, Felipe-Andres Piedra, Letisha Aideyan, Trevor Mcbride, Matthew Robertson, Hannah L. Johnson, Gina Marie Aloisio, David Henke, Cristian Coarfa, Fabio Stossi, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Joseph Petrosino, Richard A. Gibbs, Vasanthi Avadhanula, Pedro A. Piedra

Research Symposium

Background: Respiratory syncytial virus (RSV) is the major viral driver of a global pediatric respiratory disease burden disproportionately borne by the poor¹. Thus, RSV, like SARS-CoV-2, combines with congenital and environmental and host-history-dependent factors to create a spectrum of disease with greatest severity most frequently occurring in those least able to procure treatment.

Methods: Here we apply whole genome sequencing and a suite of other molecular biological techniques to survey host-virus dynamics in infections of two distinct cell lines (HEp2 and A549) with four strains representative of known RSV genetic diversity.

Results: We observed non-gradient patterns of RSV …

Effects Of 11-Kt And Prolactin On Gene Expression, Parental Care Behaviour And Immune Response In Male Bluegill Sunfish., Adriano A P Da Cunha

Electronic Thesis and Dissertation Repository

Parental care is very critical for reproduction in species that provide it. Hormones such as prolactin and androgens play a crucial role in parenting and reproductive behaviours. In mammals and birds, prolactin’s role in parental care is well-established; it stimulates milk production and stimulates attachment to newborns by its release in the preoptic area of the hypothalamus (POA), among other functions. Androgens, on the other hand, are commonly associated with male secondary sex characteristics, territoriality, and aggressiveness in mammals and birds. There are similar reports of prolactin and androgen effects in fish, but there are fewer studies. I investigated if …

Physiological And Transcriptomic Responses Of Two Artemisia Californica Populations To Drought: Implications For Restoring Drought-Resilient Native Communities, Hagop S. Atamian Dr., Jennifer L. Funk

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

As climate change brings drier and more variable rainfall patterns to many arid and semi-arid regions, land managers must re-assemble appropriate plant communities for these conditions. Transcriptome sequencing can elucidate the molecular mechanisms underlying plant responses to changing environmental conditions, potentially enhancing our ability to screen suitable genotypes and species for restoration. We examined physiological and morphological traits and transcriptome sequences of coastal and inland populations of California sagebrush (Artemisia californica), a critical shrub used to restore coastal sage scrub vegetation communities, grown under low and high rainfall environments. The populations are located approximately 36 km apart but …

Protocol To Identify The Core Gene Supported By An Essential Gene In E. Coli Bacteria Using A Genome-Wide Suppressor Screen, Isao Masuda, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

We describe here a genome-wide screening approach to identify the most critical core reaction among a network of many that are supported by an essential gene to establish cell viability. We describe steps for maintenance plasmid construction, knockout cell construction, and phenotype validation. We then detail isolation of suppressors, whole-genome sequencing analysis, and reconstruction of CRISPR mutants. We focus on E. coli trmD, which encodes an essential methyl transferase that synthesizes m1G37 on the 3'-side of the tRNA anticodon. For complete details on the use and execution of this protocol, please refer to Masuda et al. (2022).

Assesment Of Antibiotic Resistant Gene Expression In Clinical Isolates Of Pseudomonas Aeruginosa, Dustin Esmond

Biology Theses

Increasing prevalence of nosocomial infections by antimicrobial resistant pathogens resulting in higher mortality rates and financial burden is of great concern. Pseudomonas aeruginosa represents one of six highly virulent “ESKAPE” pathogens that exhibit considerable intrinsic drug resistance as well as mechanisms for acquiring further resistance. As many of these mechanisms are regulated through gene expression, we sought to identify regulatory strategies and patterns at play in 23 clinical isolates collected from Baku, Azerbaijan and Tyler, Texas, USA. Real-time quantitative polymerase chain reaction was performed on six gene targets implicated in resistance and contrasted with antibiotic phenotypes. We found AmpC cephalosporinase …

Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche

Pharmaceutical Sciences (MS) Theses

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells (HMECs) were …

Up-Regulation Of Apoptotic- And Cell Survival-Related Gene Pathways Following Exposures Of Western Corn Rootworm To B. Thuringiensis Crystalline Pesticidal Proteins In Transgenic Maize Roots, Brad S. Coates, Emeline Deleury, Aaron J. Gassmann, Bruce E. Hibbard, Lance Meinke, Nicholas J. Miller, Jennifer L. Petzold-Maxwell, B. Wade French, Thomas W. Sappington, Blair D. Siegfried, Thomas Guillemaud

Department of Entomology: Faculty Publications

Background: Resistance of pest insect species to insecticides, including B. thuringiensis (Bt) pesticidal proteins expressed by transgenic plants, is a threat to global food security. Despite the western corn rootworm, Diabrotica virgifera virgifera, being a major pest of maize and having populations showing increasing levels of resistance to hybrids expressing Bt pesticidal proteins, the cell mechanisms leading to mortality are not fully understood.

Results: Twenty unique RNA-seq libraries from the Bt susceptible D. v. virgifera inbred line Ped12, representing all growth stages and a range of different adult and larval exposures, were assembled into a reference transcriptome. Ten-day exposures …

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 …

Characterizing Adaptive Non-Coding Changes In The Regulation Of Human Gene Expression, Jason Pizzollo

Doctoral Dissertations

Differential patterns of gene expression contribute to phenotypic differences between species. Understanding evolutionary changes in gene regulatory elements can help explain traits that separate humans from closely related species. Here, in two separate studies, we investigate gene expression and gene regulatory differences between humans our closest living evolutionary relatives, chimpanzees, in the context of uniquely human traits: increased susceptibility to epithelial cancers and neural developmental and functional processes that underlie our increased cognitive capacity. Using genomic methods to study gene expression and open chromatin, we compare human and chimpanzee responses to a serum challenge, an assay that that mimics patterns …

De-Coding The Impact Of Evolved Changes In Gene Expression And Cellular Phenotype On Primate Evolution, Trisha Zintel

Doctoral Dissertations

The goal of the dissertation work outlined here was to investigate the influence of proximal processes contributing to evolutionary differences in phenotypes among primate species. There are numerous previous comparative analyses of gene expression between primate brain regions. However, primate brain tissue samples are relatively rare, and my results have contributed to the pre-existing data on more well-studied primates (i.e. humans, chimpanzees, macaques, marmosets) as well as produced information on more rarely-studied primates (i.e. patas monkey, siamang, spider monkey). Additionally, the primary visual cortex has not previously been as extensively studied at the level of gene expression as other brain …

Interspecific Gene Flow Potentiates Adaptive Evolution In A Hybrid Zone Formed Between Pinus Strobiformis And Pinus Flexilis, Mitra Menon

Theses and Dissertations

Species range margins are often characterised by high degrees of habitat fragmentation resulting in low genetic diversity and higher gene flow from populations at the core of the species range. Interspecific gene flow from a closely related species with abutting range margins can increase standing genetic diversity and generate novel allelic combinations thereby alleviating limits to adaptive evolution in range margin populations. Hybridization driven interspecific gene flow has played a key role in the demographic history of several conifer due to their life history characteristics such as weak crossability barriers and long generation times. Nevertheless, demonstrating whether introgression is adaptive …

Transcriptomic Profiling Of Postmortem Prefrontal Cortex And Nucleus Accumbens From Chronic Alcohol Abusers., Eric S. Vornholt

Theses and Dissertations

Alcohol use disorder (AUD) is a debilitating psychiatric illness that develops from a combination of genetic and environmental factors. While it is well documented that AUD is heritable, the shift from recreational alcohol use to abuse/dependence is poorly understood. In this dissertation, using postmortem brain tissue from individuals with alcohol dependence (AD), we profiled the genome-wide expression of circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) to better understand the impact of gene expression on the development of AUD. To achieve this, we performed two independent studies that explore transcriptome differences between AD cases and controls. The first of …

Implication Of Spiritual Network Support System In Epigenomic Modulation And Health Trajectory, Laurens Holmes Jr., Chinacherem Chinaka, Hikma Elmi, Kerti Deepika, Lavisha Palaez, Michael Enwere, Olumuyiwa T. Akinola, Kirk W. Dabnet

Community & Environmental Health Faculty Publications

With challenges in understanding the multifactorial etiologies of disease and individual treatment effect heterogeneities over the past four decades, much has been acquired on how physical, chemical and social environments a ffect human health, predisposing certain subpopulations to adverse health outcomes, especially the socio-environmentally disadvantaged (SED). Current translational data on gene and adverse environment interaction have revealed how adverse gene-environment interaction, termed aberrant epigenomic modulation, translates into impaired gene expression via messenger ribonucleic acid (mRNA) dysregulation, reflecting abnormal protein synthesis and hence dysfunctional cellular differentiation and maturation. The environmental influence on gene expression observed in most literature includes physical, chemical, …

Response Of Early Life Stage Homarus Americanus To Ocean Warming And Acidification: An Interpopulation Comparison, Maura K. Niemisto

Electronic Theses and Dissertations

Anthropogenic carbon released into the atmosphere is driving rapid, concurrent increases in temperature and acidity across the world’s oceans, most prominently in northern latitudes. The geographic range of the iconic American lobster (Homarus americanus) spans a steep thermal gradient and one of the most rapidly warming oceanic environments. Understanding the interactive effects of ocean warming and acidification on this species’ most vulnerable early life stages is important to predict its response to climate change on a stage-specific and population level. This study compares the responses of lobster larvae from two sub-populations spanning New England’s north-south temperature gradient (southern …

Tissue-Specific Transcriptome For Poeciliopsis Prolifica Reveals Evidence For Genetic Adaptation Related To The Evolution Of A Placental Fish, Nathaniel K. Jue, Robert J. Foley, David N. Reznick, Rachel J. O'Neill, Michael J. O'Neill

Nathaniel Jue

The Genome Of Austrofundulus Limnaeus Offers Insights Into Extreme Vertebrate Stress Tolerance And Embryonic Development, Josiah Tad Wagner, Param Priya Singh, Amie L. Romney, Claire L. Riggs, Patrick Minx, Steven Cody Woll, Jake Roush, Wesley C. Warren, Anne Brunet, Jason E. Podrabsky

Center for Life in Extreme Environments Publications

Background: The annual killifish Austrofundulus limnaeus inhabits ephemeral ponds in northern Venezuela, South America, and is an emerging extremophile model for vertebrate diapause, stress tolerance, and evolution. Embryos of A. limnaeus regularly experience extended periods of desiccation and anoxia as a part of their natural history and have unique metabolic and developmental adaptations. Currently, there are limited genomic resources available for gene expression and evolutionary studies that can take advantage of A. limnaeus as a unique model system.

Results: We describe the first draft genome sequence of A. limnaeus. The genome was assembled de novo using a merged assembly strategy …

Chromatin Accessibility Dynamics In The Arabidopsis Root Epidermis And Endodermis During Cold Acclimation, Shawn Hoogstra

Electronic Thesis and Dissertation Repository

Understanding cell-type specific transcriptional responses to environmental conditions is limited by a lack of knowledge of transcriptional control due to epigenetic dynamics. Additionally, cell-type analyses are limited by difficulties in applying current technologies to single cell-types. A novel DNase-seq protocol and analysis procedure, deemed DNase-DTS, was developed to identify DHSs in the Arabidopsis epidermis and endodermis under control and cold acclimation conditions. Results identified thousands of DHSs within each cell-type and experimental condition. DHSs showed strong association to gene expression, DNA methylation, and histone modifications. A priori mapping of existing DNA binding motifs within accessible genes and the cold C-repeat/dehydration …

Transcriptional Analysis Of Abdominal Fat In Chickens Divergently Selected On Bodyweight At Two Ages Reveals Novel Mechanisms Controlling Adiposity: Validating Visceral Adipose Tissue As A Dynamic Endocrine And Metabolic Organ, Christopher W. Resnyk, Wilfrid Carré, Xiaofei Wang, Tom E. Porter, J. Simon, Elisabeth Le Bihan-Duval, Michel J. Duclos, Sammy E. Aggrey, Larry A. Cogburn

Biology Faculty Research

Background

Decades of intensive genetic selection in the domestic chicken (Gallus gallus domesticus) have enabled the remarkable rapid growth of today’s broiler (meat-type) chickens. However, this enhanced growth rate was accompanied by several unfavorable traits (i.e., increased visceral fatness, leg weakness, and disorders of metabolism and reproduction). The present descriptive analysis of the abdominal fat transcriptome aimed to identify functional genes and biological pathways that likely contribute to an extreme difference in visceral fatness of divergently selected broiler chickens.

Methods

We used the Del-Mar 14 K Chicken Integrated Systems microarray to take time-course snapshots of global gene transcription …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Sivasai Balivada, Chanran K. Ganta, Yongqing Zhang, Hitesh N. Pawar, Richard J. Ortiz, Kevin G. Becker, Arshad M. Khan, Michael J. Kenney

Arshad M. Khan, Ph.D.

Statistical Methods For Two Problems In Cancer Research: Analysis Of Rna-Seq Data From Archival Samples And Characterization Of Onset Of Multiple Primary Cancers, Jialu Li

Dissertations & Theses (Open Access)

My dissertation is focused on quantitative methodology development and application for two important topics in translational and clinical cancer research.

The first topic was motivated by the challenge of applying transcriptome sequencing (RNA-seq) to formalin-fixation and paraffin-embedding (FFPE) tumor samples for reliable diagnostic development. We designed a biospecimen study to directly compare gene expression results from different protocols to prepare libraries for RNA-seq from human breast cancer tissues, with randomization to fresh-frozen (FF) or FFPE conditions. To comprehensively evaluate the FFPE RNA-seq data quality for expression profiling, we developed multiple computational methods for assessment, such as the uniformity and continuity …

Hippocampal Epigenetic Changes In A Mouse Model Of Fetal Alcohol Spectrum Disorders, Eric J. Chater-Diehl

Electronic Thesis and Dissertation Repository

Fetal alcohol spectrum disorders (FASD) refers to the neurological, developmental, and behavioural abnormalities arising from in utero ethanol exposure. These abnormities included attention deficit, anxiety, and learning and memory impairment persisting into adulthood. The molecular mechanisms of such persistent behavioural changes remain unknown and are an area of intense research. In this thesis, mice were exposed to ethanol during the third trimester equivalent, the peak of synaptic development. Following this exposure, genome-wide epigenetic and gene expression and changes in the hippocampus were assessed in adult (70 day old) mice.

In the first experiment, genome-wide trimethylation of histone H3 at histone …

A Gene-Based Association Method For Mapping Traits Using Reference Transcriptome Data, Eric R. Gamazon, Heather Wheeler, Kaanan P. Shah, Sahar V. Mozaffari, Keston Aquino-Michaels, Robert J. Carroll, Anne E. Eyler, Joshua C. Denny, Dan L. Nicolae, Nancy J. Cox, Hae Kyung Im

Heather Wheeler

Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual’s genetic profile and correlates ‘imputed’ gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys …

Differential Expression Of Cyb5a In Chinese And European Pig Breeds Due To Genetic Variations In The Promoter Region..Pdf, Ying Bai, Jibin Zhang, Y Xue, Yl Peng, Gang Chen, Meiying Fang

Jibin Zhang

Leveraging Global Gene Expression Patterns To Predict Expression Of Unmeasured Genes, James Rudd, René A. Zelaya, Eugene Demidenko, Ellen L. Goode, Casey S. Greene S. Greene, Jennifer A. Doherty

Dartmouth Scholarship

BackgroundLarge collections of paraffin-embedded tissue represent a rich resource to test hypotheses based on gene expression patterns; however, measurement of genome-wide expression is cost-prohibitive on a large scale. Using the known expression correlation structure within a given disease type (in this case, high grade serous ovarian cancer; HGSC), we sought to identify reduced sets of directly measured (DM) genes which could accurately predict the expression of a maximized number of unmeasured genes.

Allosteric Inhibition Of A Stem Cell Rna-Binding Protein By An Intermediary Metabolite, Carina Clingman, Laura Deveau, Samantha Hay, Ryan Genga, Shivender Shandilya, Francesca Massi, Sean Ryder

Sean P. Ryder

Gene expression and metabolism are coupled at numerous levels. Cells must sense and respond to nutrients in their environment, and specialized cells must synthesize metabolic products required for their function. Pluripotent stem cells have the ability to differentiate into a wide variety of specialized cells. How metabolic state contributes to stem cell differentiation is not understood. In this study, we show that RNA-binding by the stem cell translation regulator Musashi-1 (MSI1) is allosterically inhibited by 18-22 carbon omega-9 monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA …

A Gene-Based Association Method For Mapping Traits Using Reference Transcriptome Data, Eric R. Gamazon, Heather Wheeler, Kaanan P. Shah, Sahar V. Mozaffari, Keston Aquino-Michaels, Robert J. Carroll, Anne E. Eyler, Joshua C. Denny, Gtex Consortium, Dan L. Nicolae, Nancy J. Cox, Hae Kyung Im

Bioinformatics Faculty Publications

Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual’s genetic profile and correlates ‘imputed’ gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype. Genetically regulated gene expression is estimated using whole-genome tissue-dependent prediction models trained with reference transcriptome data sets. PrediXcan enjoys …

A Search For Parent-Of-Origin Effects On Honey Bee Gene Expression, Sarah D. Kocher, Jennifer M. Tsuruda, Joshua D. Gibson, Christine M. Emore, Miguel E. Arechavaleta-Velasco, David C. Queller, Joan E. Strassmann, Christina M. Grozinger, Michael R. Gribskov, Phillip San Miguel, Rick Westerman, Greg J. Hunt

Biology Faculty Publications & Presentations

Parent-specific gene expression (PSGE) is little known outside of mammals and plants. PSGE occurs when the expression level of a gene depends on whether an allele was inherited from the mother or the father. Kin selection theory predicts that there should be extensive PSGE in social insects because social insect parents can gain inclusive fitness benefits by silencing parental alleles in female offspring. We searched for evidence of PSGE in honey bees using transcriptomes from reciprocal crosses between European and Africanized strains. We found 46 transcripts with significant parent-of-origin effects on gene expression, many of which overexpressed the maternal allele. …

Transcriptome Analysis Of Listeria Monocytogenes Exposed To Biocide Stress Reveals A Multi-System Response Involving Cell Wall Synthesis, Sugar Uptake, And Motility, Aidan Casey, Edward M. Fox, Stephan Schmitz-Esser, Aidan Coffey, Olivia Mcauliffe, Kieran Jordan

Department of Biological Sciences Publications

Listeria monocytogenes is a virulent food-borne pathogen most often associated with the consumption of “ready-to-eat” foods. The organism is a common contaminant of food processing plants where it may persist for extended periods of time. A commonly used approach for the control of Listeria monocytogenes in the processing environment is the application of biocides such as quaternary ammonium compounds. In this study, the transcriptomic response of a persistent strain of L. monocytogenes (strain 6179) on exposure to a sub-lethal concentration of the quaternary ammonium compound benzethonium chloride (BZT) was assessed. Using RNA-Seq, gene expression levels were quantified by sequencing …

Genome-Wide Sequencing Of Small Rnas Reveals A Tissue-Specific Loss Of Conserved Microrna Families In Echinococcus Granulosus, Yun Bai, Zhuangzhi Zhang, Lei Jin, Hui Kang, Yongquiang Zhu, Lu Zhang, Xia Li, Fengshou Ma, Li Zhao, Et Al.

PCOM Scholarly Papers

Background: MicroRNAs (miRNAs) are important post-transcriptional regulators which control growth and development in eukaryotes. The cestode Echinococcus granulosus has a complex life-cycle involving different development stages but the mechanisms underpinning this development, including the involvement of miRNAs, remain unknown. Results: Using Illumina next generation sequencing technology, we sequenced at the genome-wide level three small RNA populations from the adult, protoscolex and cyst membrane of E. granulosus. A total of 94 pre-miRNA candidates (coding 91 mature miRNAs and 39 miRNA stars) were in silico predicted. Through comparison of expression profiles, we found 42 mature miRNAs and 23 miRNA stars expressed with …

Egonet: Identification Of Human Disease Ego-Network Modules, Rendong Yang, Yun Bai, Zhaohui Qin, Tianwei Yu

PCOM Scholarly Papers

Background: Mining novel biomarkers from gene expression profiles for accurate disease classification is challenging due to small sample size and high noise in gene expression measurements. Several studies have proposed integrated analyses of microarray data and protein-protein interaction (PPI) networks to find diagnostic subnetwork markers. However, the neighborhood relationship among network member genes has not been fully considered by those methods, leaving many potential gene markers unidentified. The main idea of this study is to take full advantage of the biological observation that genes associated with the same or similar diseases commonly reside in the same neighborhood of molecular networks.Results: …