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Articles 1 - 30 of 30
Full-Text Articles in Genetics and Genomics
Unseen Science: Modern Discoveries Too Far Away Or Tiny For Human Eyes, Lucy Huang
Unseen Science: Modern Discoveries Too Far Away Or Tiny For Human Eyes, Lucy Huang
Capstones
As science has progressed, scientists have realized that evidence goes beyond the realms of physical sight. Whether it is too small or difficult to find, scientists have developed different ways to get around this problem. We see this in cancer genomics and in extrasolar planetary research. Scientists use what they know and what they measure to validate their work.
https://lucy-huang-9tge.squarespace.com/
Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande
Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande
KGI Theses and Dissertations
Huntington’s disease (HD) is a debilitating neurodegenerative disorder with a complex pathophysiology. Despite extensive studies to study the disease, the sequence of events through which mutant Huntingtin (mHtt) protein executes its action still remains elusive. The phenotype of HD is an outcome of numerous processes initiated by the mHtt protein along with other proteins that act as either suppressors or enhancers of the effects of mHtt protein and PolyQ aggregates. Utilizing an integrative systems biology approach, I construct and analyze a Huntington’s disease integrome using human orthologs of protein interactors of wild type and mHtt protein. Analysis of this integrome …
Bioinformatic And Experimental Approaches For Deeper Metaproteomic Characterization Of Complex Environmental Samples, Ramsunder Mahadevan Iyer
Bioinformatic And Experimental Approaches For Deeper Metaproteomic Characterization Of Complex Environmental Samples, Ramsunder Mahadevan Iyer
Doctoral Dissertations
The coupling of high performance multi-dimensional liquid chromatography and tandem mass spectrometry for characterization of microbial proteins from complex environmental samples has paved the way for a new era in scientific discovery. The field of metaproteomics, which is the study of protein suite of all the organisms in a biological system, has taken a tremendous leap with the introduction of high-throughput proteomics. However, with corresponding increase in sample complexity, novel challenges have been raised with respect to efficient peptide separation via chromatography and bioinformatic analysis of the resulting high throughput data. In this dissertation, various aspects of metaproteomic characterization, including …
Identifying Genetic Factors Influencing Sperm Mobility Phenotype In Chicken Using Genome Wide Association Studies, Primordial Germ Cell Transplantation, And Rnaseq., Sohita Ojha
Graduate Theses and Dissertations
Sperm mobility is a major determinant of male fertility in chicken. In spite of low heritability of reproductive traits, sperm mobility has high heritability index which suggests presence of quantitative trait loci (QTLs) governing the trait. Our research focused on three objectives: i) to identify the QTLs affecting low mobility phenotype in chicken, ii) to understand the impact of Sertoli-cells and germ cells interactions in influencing the mobility phenotype and iii) to identify the genes and gene networks differentially expressed in male and female PGCs. To detect the QTLs, genome wide association studies (GWAS) was conducted which revealed the presence …
Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh
Dissertations & Theses (Open Access)
Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic …
Development, Evaluation, And Application Of A Novel Error Correction Method For Next Generation Sequencing Data, Isaac Akogwu
Development, Evaluation, And Application Of A Novel Error Correction Method For Next Generation Sequencing Data, Isaac Akogwu
Dissertations
Tremendous evolvement in sequencing technologies and the vast availability of data due to decreasing cost of Next-Generation-Sequencing (NGS) has availed scientists the opportunity to address a wide variety of evolutionary and biological issues. NGS uses massively parallel technology to accelerate the process at the expense of accuracy and read length in comparison to earlier Sanger methods. Therefore, computational limitations exist in how much analysis and information can be gleaned from the data without performing some form of error correction.
Error correction process is laborious and consumes a lot of computational resources. Despite the existence of many NGS data error correction …
Chromatin Accessibility Dynamics In The Arabidopsis Root Epidermis And Endodermis During Cold Acclimation, Shawn Hoogstra
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 …
The Role Of Histone H2a.Z Abundance In Modulating Responses To Phosphorus Deficiency In Rice, Sara Zahraeifard
The Role Of Histone H2a.Z Abundance In Modulating Responses To Phosphorus Deficiency In Rice, Sara Zahraeifard
LSU Doctoral Dissertations
Histone variants contribute to chromatin complexity by creating specialized nucleosomes. Here, to investigate the pattern of H2A.Z histone variant distribution and its role in modulating gene expression in rice (Oryza sativa L.), we performed genome-wide profiling of ARP6-dependent H2A.Z deposition in rice seedlings. We demonstrated that under controlled conditions, the majority of H2A.Z deposition is within protein-coding genes (PCG), and the most highly expressed genes are enriched with H2A.Z at their 5’ ends near the transcription start site (TSS), whereas the medium- to low-expressed genes contain H2A.Z across the entire gene. Based on H2A.Z deposition, we categorized genes into …
Multiple Testing Correction With Repeated Correlated Outcomes: Applications To Epigenetics, Katie Leap
Multiple Testing Correction With Repeated Correlated Outcomes: Applications To Epigenetics, Katie Leap
Masters Theses
Epigenetic changes (specifically DNA methylation) have been associated with adverse health outcomes; however, unlike genetic markers that are fixed over the lifetime of an individual, methylation can change. Given that there are a large number of methylation sites, measuring them repeatedly introduces multiple testing problems beyond those that exist in a static genetic context. Using simulations of epigenetic data, we considered different methods of controlling the false discovery rate. We considered several underlying associations between an exposure and methylation over time.
We found that testing each site with a linear mixed effects model and then controlling the false discovery rate …
Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta
Exploring Biological Heterogeneity And Its Consequences At Tissue And Cellular Scales Through Mathematical And Computational Modeling, Romica Kerketta
Biomedical Sciences ETDs
This dissertation explores the effects of heterogeneity across different biological scales in cancer as well as normal cells. At the tissue scale, we investigated the variability present in the tumor microenvironment and its effect on patient chemotherapeutic outcomes using a mathematical model of drug transport. We found that parameters such as tumor blood perfusion and radius of blood vessel had an impact on the tumor cytotoxicity. This indicated that the physical microenvironment of the tumor is an important regulator of the tumor response to chemotherapy. At the cellular scale, we investigated the heterogeneity present on the membrane landscape of ErbB2 …
Computational Investigation Of The Pore Formation Mechanism Of Beta-Hairpin Antimicrobial Peptides, Richard Lipkin
Computational Investigation Of The Pore Formation Mechanism Of Beta-Hairpin Antimicrobial Peptides, Richard Lipkin
Dissertations, Theses, and Capstone Projects
β-hairpin antimicrobial peptides (AMPs) are small, usually cationic peptides that provide innate biological defenses against multiple agents. They have been proposed as the basis for novel antibiotics, but their pore formation has not been directly observed on a molecular level. We review previous computational studies of peptide-induced membrane pore formation and report several new molecular dynamics simulations of β-hairpin AMPs to elucidate their pore formation mechanism. We simulated β-barrels of various AMPs in anionic implicit membranes, finding that most of the AMPs’ β-barrels were not as stable as those of protegrin. We also performed an optimization study of protegrin β-barrels …
A Combined Computational Strategy Of Sequence And Structural Analysis Predicts The Existence Of A Functional Eicosanoid Pathway In Drosophila Melanogaster, Michael Scarpati
A Combined Computational Strategy Of Sequence And Structural Analysis Predicts The Existence Of A Functional Eicosanoid Pathway In Drosophila Melanogaster, Michael Scarpati
Dissertations, Theses, and Capstone Projects
With increased understanding of their roles in signal transduction and metabolism, eicosanoids have emerged as important players in human health and disease. Mammalian prostanoids and related lipid mediators perform varied functions in different tissues and organs. Synthesized through the oxygenation of C20 polyunsaturated fatty acids, mammalian eicosanoids are both pro- and anti-inflammatory. The physiological contexts in which eicosanoid family members act at the cellular level are not well understood. In this study, we examined whether the genome of Drosophila melanogaster, a powerful model for innate immunity and inflammation, codes for the enzymes required for eicosanoid biosynthesis. We report the …
Comparative Phylogeographic, Population Genomic, And Selection Inference With Development Of Hierarchical Co-Demographic Models, Alexander Xue
Comparative Phylogeographic, Population Genomic, And Selection Inference With Development Of Hierarchical Co-Demographic Models, Alexander Xue
Dissertations, Theses, and Capstone Projects
Comparing demographic histories across assemblages of populations, species, and sister pairs has been a focus in phylogeography since its inception. Initial approaches utilized organelle genetic data and involved qualitative comparisons of genetic patterns for evaluating hypotheses of shared evolutionary responses to past environmental changes. This endeavor has progressed with coalescent model-based statistical techniques and advances in next-generation sequencing, yet there remains a need for methods that can analyze aggregated genomic-scale data from non-model organisms within a unified framework that considers individual taxon uncertainty and variance. To this end, the aggregate site frequency spectrum (aSFS), an expansion of the site frequency …
Machine Learning Based Protein Sequence To (Un)Structure Mapping And Interaction Prediction, Sumaiya Iqbal
Machine Learning Based Protein Sequence To (Un)Structure Mapping And Interaction Prediction, Sumaiya Iqbal
University of New Orleans Theses and Dissertations
Proteins are the fundamental macromolecules within a cell that carry out most of the biological functions. The computational study of protein structure and its functions, using machine learning and data analytics, is elemental in advancing the life-science research due to the fast-growing biological data and the extensive complexities involved in their analyses towards discovering meaningful insights. Mapping of protein’s primary sequence is not only limited to its structure, we extend that to its disordered component known as Intrinsically Disordered Proteins or Regions in proteins (IDPs/IDRs), and hence the involved dynamics, which help us explain complex interaction within a cell that …
On The Construction And Interpretation Of Fitness Landscapes For Hiv: A Computational Perspective, Elizabeth Grace Johnson
On The Construction And Interpretation Of Fitness Landscapes For Hiv: A Computational Perspective, Elizabeth Grace Johnson
Doctoral Dissertations
To identify vulnerable viral targets to incorporate into an immunogen, fitness landscapes for the viral proteome have been constructed. These landscapes describe the sum or synergistic replicative cost exacted on the virus for any combination of non-synonymous mutations. Here we attempt to assess the robustness of current computational methods for measuring the fitness cost of HIV polymorphisms in these landscapes. We also address in the following chapters assumptions and shortcomings that may underlie current landscape's uneven ability to predict fitness effects.
In the first chapter, I appraise the robustness of current frame-works that derive fitness costs from patient sequence data. …
Statistical Methods For High Dimensional Data Arising From Large Epidemiological Studies, Hui Xu
Statistical Methods For High Dimensional Data Arising From Large Epidemiological Studies, Hui Xu
Doctoral Dissertations
In this thesis, we propose statistical models for addressing commonly encountered data types and study designs in large epidemiologic investigations aimed at understanding the molecular basis of complex disorders. The motivating applications come from diverse disease areas in Women's Health, including the study of type II diabetes in the Women's Health Initiative (WHI), invasive breast cancer in the Nurses' Health Study and the study of the metabolomic underpinnings of cardiovascular disease in the WHI. We have also put significant effort into making the implementation of the proposed methods accessible through freely available, user-friendly software packages in R. The first chapter …
Isolation And Comparative Genomic Analysis Of Final Third Of Satis Genome, Kelly Hartigan, Nicole Curnutt, Matthew Mcdermut
Isolation And Comparative Genomic Analysis Of Final Third Of Satis Genome, Kelly Hartigan, Nicole Curnutt, Matthew Mcdermut
Undergraduate Research Symposium Posters
A highly novel Streptomyces phage, Satis, was isolated from a direct environmental sample collected from outside Danforth House on the Washington University campus. Satis infects bacterial species Streptomyces lividans producing pinpoint, cloudy plaques less than 1mm in diameter. Electron microscope data shows rare atypical physical features. Rather than the common octahedral capsid shape, Satis has a prolate head with visible cross-linked hexagonal protein structure and average measurements of 285 nm by 47 nm with a long, flexible tail measuring 268 nm. Upon sequencing, it was found that Satis contains the longest phage genome discovered to date through the SEA-PHAGE program …
Using Phylogenetic Comparative Methods To Understand Diversification And Geographic Range Evolution, Kathryn Aurora Massana
Using Phylogenetic Comparative Methods To Understand Diversification And Geographic Range Evolution, Kathryn Aurora Massana
Doctoral Dissertations
Two key processes that have been modeled in a phylogenetic comparative framework are diversification and historical biogeography. Many questions arise on what process have shaped the abundance (or lack) of species we see today and what influences their survival and interconnectedness with other species. Many methods have been developed to answer these questions. Over the past several decades there has been a rise in parametric modeling and development of more adequate frameworks to answer biological questions of interest. However, many models still lack the incorporation of ecological, mainly biotic factors, which influence the evolution and ecology of species, while accounting …
Hybridization Dynamics Of A Newly Discovered Parrotfish Swarm In The Tropical Eastern Pacific, Robert Barron
Hybridization Dynamics Of A Newly Discovered Parrotfish Swarm In The Tropical Eastern Pacific, Robert Barron
Honors Projects
Hybrid zones and their dynamics are important in the understanding of the genetic basis of reproductive isolation and speciation. This study seeks to investigate the hybridization dynamics of a Scarus hybrid swarm within the Tropical Eastern Pacific (TEP) that includes four phenotypically distinct species: S. perrico, S. ghobban, S. rubroviolaceus, and S. compressus. Genetic and population structure analyses of four nuclear loci and a mitochondrial locus revealed that one of the four species, S. compressus, was the result of two different hybrid crosses: S. perrico ✕ S. rubroviolaceus and S. perrico ✕ S. ghobban. A …
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 …
Phylogenetic Studies Of The Madagascan Freshwater Crabs (Potamoidea, Potamonautidae, Deckeniinae), Rainee Stevens
Phylogenetic Studies Of The Madagascan Freshwater Crabs (Potamoidea, Potamonautidae, Deckeniinae), Rainee Stevens
All NMU Master's Theses
Relationships within the Madagascan freshwater crab fauna were examined based on unstudied specimens from all parts of Madagascar. This study allowed the examination of the validity of existing genera and species, and identified potential new taxa. The new specimens provided phylogenetic and evolutionary data, as well as new insights into the distribution patterns of the Malagasy freshwater crab fauna. In addition, the large number of new localities from previously unsurveyed areas of Madagascar allowed the construction of updated distribution maps.
The present analysis included 62 unidentified specimens plus 13 identified species of Malagasy freshwater crab taxa that had already been …
Transcriptome Approach For Identifying Potential Biomarkers For Endocrine Disruption Due To Crude Oil Exposure Using Killifish (Fundulus Heteroclitus)., Frank J. Zadlock Iv
Transcriptome Approach For Identifying Potential Biomarkers For Endocrine Disruption Due To Crude Oil Exposure Using Killifish (Fundulus Heteroclitus)., Frank J. Zadlock Iv
Seton Hall University Dissertations and Theses (ETDs)
The killifish, Fundulus heteroclitus, is a common fish model in aquatic toxicology. However, little is known in this organism about how endocrine disrupting compounds, (EDCs) including polycyclic aromatic hydrocarbons (PAHs), impact the reproductive status from a molecular standpoint. The objective of this project is to apply high throughput sequencing to F. heteroclitus testes to examine the molecular mechanisms that impair reproduction when exposed to crude oil. First, a crude oil exposure experiment was conducted. Following exposure, semi-quantitative PCR was performed to detect changes in gene expression of the following genes known to respond to EDCs: gonadal aromatase (CYP19a), vitellogenin …
Uncovering Candidate Cold Tolerance Genes In Maize (Zea Mays), Raeann N. Goering
Uncovering Candidate Cold Tolerance Genes In Maize (Zea Mays), Raeann N. Goering
Departmental Honors Projects
With booming populations soon to overwhelm the world's food production capabilities, studying what makes crop organisms, like maize, efficient is crucial to ensure that the demand for food is met. Planting earlier in the spring would lengthen the crop season and produce larger yields provided the crop is tolerant to early spring’s low temperatures. Plants can adjust to abiotic stresses through biochemical changes controlled by transcription of genes. Trained plants can be produced by pre-exposing them to a lesser stress, allowing them to recover, then exposing them to a greater, longer stress. It is hypothesized that trained plants will tolerate …
K-Mer Analysis Pipeline For Classification Of Dna Sequences From Metagenomic Samples, Russell Kaehler
K-Mer Analysis Pipeline For Classification Of Dna Sequences From Metagenomic Samples, Russell Kaehler
Graduate Student Theses, Dissertations, & Professional Papers
Biological sequence datasets are increasing at a prodigious rate. The volume of data in these datasets surpasses what is observed in many other fields of science. New developments wherein metagenomic DNA from complex bacterial communities is recovered and sequenced are producing a new kind of data known as metagenomic data, which is comprised of DNA fragments from many genomes. Developing a utility to analyze such metagenomic data and predict the sample class from which it originated has many possible implications for ecological and medical applications. Within this document is a description of a series of analytical techniques used to process …
Characterization Of A Large Vertebrate Genome And Homomorphic Sex Chromosomes In The Axolotl, Ambystoma Mexicanum, Melissa Keinath
Characterization Of A Large Vertebrate Genome And Homomorphic Sex Chromosomes In The Axolotl, Ambystoma Mexicanum, Melissa Keinath
Theses and Dissertations--Biology
Changes in the structure, content and morphology of chromosomes accumulate over evolutionary time and contribute to cell, developmental and organismal biology. The axolotl (Ambystoma mexicanum) is an important model for studying these changes because: 1) it provides important phylogenetic perspective for reconstructing the evolution of vertebrate genomes and amphibian karyotypes, 2) its genome has evolved to a large size (~10X larger than human) but has maintained gene orders, and 3) it possesses potentially young sex chromosomes that have not undergone extensive differentiation in the structure that is typical of many other vertebrate sex chromosomes (e.g. mammalian XY chromosomes …
Dynamics Of Gene Networks In Cancer Research, Paul Scott
Dynamics Of Gene Networks In Cancer Research, Paul Scott
Electronic Theses and Dissertations
Cancer prevention treatments are being researched to see if an optimized treatment schedule would decrease the likelihood of a person being diagnosed with cancer. To do this we are looking at genes involved in the cell cycle and how they interact with one another. Through each gene expression during the life of a normal cell we get an understanding of the gene interactions and test these against those of a cancerous cell. First we construct a simplified network model of the normal gene network. Once we have this model we translate it into a transition matrix and force changes on …
Evolution Of Equine Arteritis Virus During Persistent Infection In The Reproductive Tract Of The Stallion And The Male Donkey, Bora Nam
Theses and Dissertations--Veterinary Science
Equine arteritis virus (EAV) establishes persistent infection in the stallion reproductive tract, and the carrier stallion continues to shed virus in semen for weeks to years or lifelong. The objective of this study was to elucidate the intra-host evolution of EAV during persistent infection in stallions. Seven EAV seronegative stallions were experimentally infected with EAV KY84 strain and followed for 726 days post-infection, and sequential clinical samples including semen were collected for virus isolation and next-generation sequencing (NGS). In addition, archived sequential semen samples from two stallions that were naturally infected with EAV KY84 for a long-period (up to 10 …
Identification Of Novel Sleep Related Genes From Large Scale Phenotyping Experiments In Mice, Shreyas Joshi
Identification Of Novel Sleep Related Genes From Large Scale Phenotyping Experiments In Mice, Shreyas Joshi
Theses and Dissertations--Biology
Humans spend a third of their lives sleeping but very little is known about the physiological and genetic mechanisms controlling sleep. Increased data from sleep phenotyping studies in mouse and other species, genetic crosses, and gene expression databases can all help improve our understanding of the process. Here, we present analysis of our own sleep data from the large-scale phenotyping program at The Jackson Laboratory (JAX), to identify the best gene candidates and phenotype predictors for influencing sleep traits.
The original knockout mouse project (KOMP) was a worldwide collaborative effort to produce embryonic stem (ES) cell lines with one of …
Genomic Perspectives On Amphibian Evolution Across Multiple Phylogenetic Scales, Paul Michael Hime
Genomic Perspectives On Amphibian Evolution Across Multiple Phylogenetic Scales, Paul Michael Hime
Theses and Dissertations--Biology
Genomes provide windows into the evolutionary histories of species. The recent accessibility of genome-scale data in non-model organisms and the proliferation of powerful statistical models are now providing unprecedented opportunities to uncover evolutionary relationships and to test hypotheses about the processes that generate and maintain biodiversity. This dissertation work reveals shallow-scale species boundaries and population genetic structure in two imperiled groups of salamanders and demonstrates that the number and information content of genomic regions used in species delimitation exert strong effects on the resulting inferences. Genome scans are employed to test hypotheses about the mechanisms of genetic sex determination in …
Network Analytics For The Mirna Regulome And Mirna-Disease Interactions, Joseph Jayakar Nalluri
Network Analytics For The Mirna Regulome And Mirna-Disease Interactions, Joseph Jayakar Nalluri
Theses and Dissertations
miRNAs are non-coding RNAs of approx. 22 nucleotides in length that inhibit gene expression at the post-transcriptional level. By virtue of this gene regulation mechanism, miRNAs play a critical role in several biological processes and patho-physiological conditions, including cancers. miRNA behavior is a result of a multi-level complex interaction network involving miRNA-mRNA, TF-miRNA-gene, and miRNA-chemical interactions; hence the precise patterns through which a miRNA regulates a certain disease(s) are still elusive. Herein, I have developed an integrative genomics methods/pipeline to (i) build a miRNA regulomics and data analytics repository, (ii) create/model these interactions into networks and use optimization techniques, motif …