Formulation Of Hybrid Knowledge-Based/Molecular Mechanics Potentials For Protein Structure Refinement And A Novel Graph Theoretical Protein Structure Comparison And Analysis Technique, 2019 University of New Orleans
Formulation Of Hybrid Knowledge-Based/Molecular Mechanics Potentials For Protein Structure Refinement And A Novel Graph Theoretical Protein Structure Comparison And Analysis Technique, Aaron Maus
University of New Orleans Theses and Dissertations
Proteins are the fundamental machinery that enables the functions of life. It is critical to understand them not just for basic biology, but also to enable medical advances. The field of protein structure prediction is concerned with developing computational techniques to predict protein structure and function from a protein’s amino acid sequence, encoded for directly in DNA, alone. Despite much progress since the first computational models in the late 1960’s, techniques for the prediction of protein structure still cannot reliably produce structures of high enough accuracy to enable desired applications such as rational drug design. Protein structure refinement ...
Transcript-Based Cloning Of Rrp46, A Regulator Of Rrna Processing And R Gene–Independent Cell Death In Barley–Powdery Mildew Interactions, Liu Xi, Matthew J. Moscou, Yan Meng, Weihui Xu, Rico A. Caldo, Miranda Shaver, Dan Nettleton, Roger P. Wise
Programmed cell death (PCD) plays a pivotal role in plant development and defense. To investigate the interaction between PCD and R gene–mediated defense, we used the 22K Barley1 GeneChip to compare and contrast time-course expression profiles of Blumeria graminis f. sp hordei (Bgh) challenged barley (Hordeum vulgare) cultivar C.I. 16151 (harboring the Mla6 powdery mildew resistance allele) and its fast neutron–derived Bgh-induced tip cell death1 mutant, bcd1. Mixed linear model analysis identified genes associated with the cell death phenotype as opposed to Rgene–mediated resistance. One-hundred fifty genes were found at the threshold P value < 0.0001 and a false discovery rate bcd1mutant. Gene Ontology and rice (Oryza ...
Gene Expression Profiling In Salmonella Choleraesuis-Infected Porcine Lung Using A Long Oligonucleotide Microarray, Shu-Hong Zhao, Daniel Kuhar, Joan K. Lunney, Harry Dawson, Catherine Guidry, Jolita J. Uthe, Shawn M. D. Bearson, Justin Recknor, Dan Nettleton, Christopher K. Tuggle
Understanding the transcriptional response to pathogenic bacterial infection within food animals is of fundamental and applied interest. To determine the transcriptional response to Salmonella enterica serovar Choleraesuis (SC) infection, a 13,297-oligonucleotide swine array was used to analyze RNA from control, 24-h postinoculation (hpi), and 48-hpi porcine lung tissue from pigs infected with SC. In total, 57 genes showed differential expression (p < 0.001; false discovery rate = 12%). Quantitative real-time PCR (qRT-PCR) of 61 genes was used to confirm the microarray results and to identify pathways responding to infection. Of the 33 genes identified by microarray analysis as differentially expressed, 23 were confirmed by qRT-PCR results. A novel finding was that two transglutaminase family genes (TGM1 and TGM3) showed dramatic increases in expression postinoculation; combined with several other apoptotic genes, they indicated the induction of apoptotic pathways during SC infection. A predominant T helper 1-type immune response occurred during infection, with interferon γ ...
Scanning Microarrays At Multiple Intensities Enhances Discovery Of Differentially Expressed Genes, 2019 Iowa State University
Scanning Microarrays At Multiple Intensities Enhances Discovery Of Differentially Expressed Genes, David S. Skibbe, Xiujuan Wang, Xuefeng Zhao, Lisa A. Borsuk, Dan Nettleton, Patrick S. Schnable
Motivation: Scanning parameters are often overlooked when optimizing microarray experiments. A scanning approach that extends the dynamic data range by acquiring multiple scans of different intensities has been developed.
Results: Data from each of three scan intensities (low, medium, high) were analyzed separately using multiple scan and linear regression approaches to identify and compare the sets of genes that exhibit statistically significant differential expression. In the multiple scan approach only one-third of the differentially expressed genes were shared among the three intensities, and each scan intensity identified unique sets of differentially expressed genes. The set of differentially expressed genes from ...
Gene Mapping Via Bulked Segregant Rna-Seq (Bsr-Seq), 2019 Iowa State University
Gene Mapping Via Bulked Segregant Rna-Seq (Bsr-Seq), Sanzhen Liu, Cheng-Ting Yeh, Ho Man Tang, Dan Nettleton, Patrick S. Schnable
Bulked segregant analysis (BSA) is an efficient method to rapidly and efficiently map genes responsible for mutant phenotypes. BSA requires access to quantitative genetic markers that are polymorphic in the mapping population. We have developed a modification of BSA (BSR-Seq) that makes use of RNA-Seq reads to efficiently map genes even in populations for which no polymorphic markers have been previously identified. Because of the digital nature of next-generation sequencing (NGS) data, it is possible to conduct de novo SNP discovery and quantitatively genotype BSA samples by analyzing the same RNA-Seq data using an empirical Bayesian approach. In addition, analysis ...
Role Of Gp120 Glycosylation In Sexual Transmission Of Hiv, 2019 University of Western Ontario
Role Of Gp120 Glycosylation In Sexual Transmission Of Hiv, Yingxue Sun, Adam Meadows, Najwa Zebian, Eric Arts, Carole Creuzenet
Western Research Forum
In chronic HIV patients, the viral populations are genetically diverse due to mutations introduced by the viral reverse transcriptase during HIV replication. However, more than 80% new infections result from single transmission founder (TF) viruses; therefore, targeting the TFs is key to control AIDS worldwide.
Gp120 is a glycosylated envelope protein required for HIV infection, propagation, and transmission. Glycans on gp120 influence HIV infectivity through their interactions with lectins, the carbohydrate-binding immune proteins in the host mucosa. To transmit sexually, viruses must overcome the lectin traps to access more target T cells.
TF viruses are less likely to ...
Reverse Engineering And Analysis Of Large Genome-Scale Gene Networks, 2019 Iowa State University
Reverse Engineering And Analysis Of Large Genome-Scale Gene Networks, Maneesha Aluru, Jaroslaw Zola, Dan Nettleton, Srinivas Aluru
Reverse engineering the whole-genome networks of complex multicellular organisms continues to remain a challenge. While simpler models easily scale to large number of genes and gene expression datasets, more accurate models are compute intensive limiting their scale of applicability. To enable fast and accurate reconstruction of large networks, we developed Tool for Inferring Network of Genes (TINGe), a parallel mutual information (MI)-based program. The novel features of our approach include: (i) B-spline-based formulation for linear-time computation of MI, (ii) a novel algorithm for direct permutation testing and (iii) development of parallel algorithms to reduce run-time and facilitate construction of ...
Salmonella Enterica Serovar Typhimurium-Infected Pigs With Different Shedding Levels Exhibit Distinct Clinical, Peripheral Cytokine And Transcriptomic Immune Response Phenotypes, 2019 Iowa State University
Salmonella Enterica Serovar Typhimurium-Infected Pigs With Different Shedding Levels Exhibit Distinct Clinical, Peripheral Cytokine And Transcriptomic Immune Response Phenotypes, Susan M. Knetter, Shawn M. D. Bearson, Ting-Hua Huang, Dason Kurkiewicz, Martine Schroyen, Dan Nettleton, Daniel Berman, Valerie Cohen, Joan K. Lunney, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Christopher K. Tuggle
Foodborne salmonellosis costs the US $2.7 billion/year, including $100.0 million in annual losses to pork producers. Pigs colonized with Salmonella are usually asymptomatic with varied severity and duration of fecal shedding. Thus, understanding the responses that result in less shedding may provide a mechanism for control. Fifty-four pigs were inoculated with Salmonella enterica serovar Typhimurium (ST) and clinical signs, fecal ST shedding, growth performance, peripheral cytokines and whole blood gene expression were measured. Persistently shedding (PS) pigs had longer pyrexia and elevated serum IL-1β, TNF-α and IFN-γ compared with low shedding (LS) pigs, while LS pigs had ...
An Application Of The Modifiable Areal Unit Problem: Optimizing Cluster Method Parameters To Produce Predictive Data For Hiv Outbreaks, Connor J. Chato, Art Fy Poon
Western Research Forum
A popular approach to study HIV outbreaks is to cluster cases based on genetic similarity. However, there is no widely-used statistical criterion which optimizes the parameters for sequence-based clustering methods. The relationship between a cluster-defining similarity threshold and it’s associated set of clusters can be analogized to the aggregation level in the Modifiable Areal Unit Problem (MAUP).
Based on the selection of aggregation level for study partitions in MAUP, we present a statistical framework to optimize the similarity threshold for pairwise distance algorithm TN93 (http://github.com/veg/tn93). We hypothesize that defining this threshold includes case ...
Genomic Analysis Of Mitochondria Of Metschnikowia, 2019 Western University
Genomic Analysis Of Mitochondria Of Metschnikowia, Dong Kyung Lee
Western Research Forum
Genomic Analysis of Mitochondria of Metschnikowia
Our current understanding of mitochondrial genomes is biased toward metazoans, which represent the majority of sequenced mitochondrial DNAs (mtDNAs). The high diversity in size, shape, and gene synteny among yeast mitochondrial genomes make them an appealing alternative to those of metazoans for studying genomic diversity and evolution. Recently, more than 60 draft-genome assemblies of large-spored Metschnikowia species have been determined. Complete mitochondrial genomes of these yeasts, however, are yet to be constructed and characterized. Therefore, I propose to construct and analyze the mitochondrial genomes of all 61 strains of large-spored Metschnikowia species.
Iron-Sulfur Cluster Biosynthesis In Methanogens, 2019 Louisiana State University and Agricultural and Mechanical College
Iron-Sulfur Cluster Biosynthesis In Methanogens, Cuiping Zhao
LSU Doctoral Dissertations
Methanogens live in a syntrophic consortium with bacteria, taking advantage of the metabolic abilities of their syntrophic partners to overcome energetic barriers and break down compounds that they cannot digest by themselves. Interspecies electron transfer, which is a major type of microbial communication in syntrophic processes, improves methanogenesis and anaerobic oxidization of methane (AOM) processes involved in syntrophic consortia. These processes have a significant impact on the global carbon cycle. Most of the essential enzymes involved in methanogenesis are iron-sulfur proteins. Iron-sulfur clusters are one of the oldest and most versatile cofactors present in all domains of life. To date ...
Stress Response To Co2 Deprivation By Arabidopsis Thaliana In Plant Cultures, 2019 Iowa State University
Stress Response To Co2 Deprivation By Arabidopsis Thaliana In Plant Cultures, Souvik Banerjee, Oskar Siemianowski, Meiling Liu, Kara R. Lind, Xinchun Tian, Dan Nettleton, Ludovico Cademartiri
After being the standard plant propagation protocol for decades, cultures of Arabidopsis thaliana sealed with Parafilm remain common today out of practicality, habit, or necessity (as in co-cultures with microorganisms). Regardless of concerns over the aeration of these cultures, no investigation has explored the CO2 transport inside these cultures and its effect on the plants. Thereby, it was impossible to assess whether Parafilm-seals used today or in thousands of older papers in the literature constitute a treatment, and whether this treatment could potentially affect the study of other treatments.For the first time we report the CO2concentrations in Parafilm-sealed cultures ...
Interchromosomal Transfer Of Immune Regulation During Infection Of Barley With The Powdery Mildew Pathogen, 2019 Iowa State University
Interchromosomal Transfer Of Immune Regulation During Infection Of Barley With The Powdery Mildew Pathogen, Priyanka Surana, Ruo Xu, Gregory Fuerst, Antony V. E. Chapman, Dan Nettleton, Roger P. Wise
Powdery mildew pathogens colonize over 9500 plant species, causing critical yield loss. The Ascomycete fungus, Blumeria graminis f. sp. hordei (Bgh), causes powdery mildew disease in barley (Hordeum vulgare L.). Successful infection begins with penetration of host epidermal cells, culminating in haustorial feeding structures, facilitating delivery of fungal effectors to the plant and exchange of nutrients from host to pathogen. We used expression Quantitative Trait Locus (eQTL) analysis to dissect the temporal control of immunity-associated gene expression in a doubled haploid barley population challenged with Bgh. Two highly significant regions possessing trans eQTL were identified near the telomeric ends of ...
Adaptive Evolution Targets A Pirna Precursor Transcription Network, 2019 University of Massachusetts Medical School
Adaptive Evolution Targets A Pirna Precursor Transcription Network, Swapnil S. Parhad, Tianxiong Yu, Gen Zhang, Nicholas P. Rice, Zhiping Weng, William E. Theurkauf
University of Massachusetts Medical School Faculty Publications
In Drosophila, transposon-silencing piRNAs are derived from heterochromatic clusters and a subset of euchromatic transposon insertions, which are transcribed from internal non-canonical initiation sites and flanking canonical promoters. Rhino binds to Deadlock, which recruits TRF2 to promote non-canonical transcription of these loci. Cuff co-localizes with Rhino and Del. The role of Cuff is less well understood, but the cuff gene shows hallmarks of adaptive evolution, which frequently targets functional interactions within host defense systems. We show that Drosophila simulans cuff is a dominant negative allele when expressed in Drosophila melanogaster, where it traps Deadlock, TRF2 and the transcriptional co-repressor CtBP ...
A Chromosome Folding Intermediate At The Condensin-To-Cohesin Transition During Telophase, 2019 University of Massachusetts Medical School
A Chromosome Folding Intermediate At The Condensin-To-Cohesin Transition During Telophase, Kristin Abramo, Anne-Laure Valton, Sergey V. Venev, Hakan Ozadam, A. Nicole Fox, Job Dekker
University of Massachusetts Medical School Faculty Publications
Chromosome folding is extensively modulated as cells progress through the cell cycle. During mitosis, condensin complexes fold chromosomes in helically arranged nested loop arrays. In interphase, the cohesin complex generates loops that can be stalled at CTCF sites leading to positioned loops and topologically associating domains (TADs), while a separate process of compartmentalization drives the spatial segregation of active and inactive chromatin domains. We used synchronized cell cultures to determine how the mitotic chromosome conformation is transformed into the interphase state. Using Hi-C, chromatin binding assays, and immunofluorescence we show that by telophase condensin-mediated loops are lost and a transient ...
Mu Transposon Insertion Sites And Meiotic Recombination Events Co-Localize With Epigenetic Marks For Open Chromatin Across The Maize Genome, Sanzhen Liu, Cheng-Ting Yeh, Tieming Ji, Kai Ying, Haiyan Wu, Ho Man Tang, Yan Fu, Daniel S. Nettleton, Patrick S. Schnable
The Mu transposon system of maize is highly active, with each of the ∼50–100 copies transposing on average once each generation. The approximately one dozen distinct Mutransposons contain highly similar ∼215 bp terminal inverted repeats (TIRs) and generate 9-bp target site duplications (TSDs) upon insertion. Using a novel genome walking strategy that uses these conserved TIRs as primer binding sites, Mu insertion sites were amplified from Mu stocks and sequenced via 454 technology. 94% of ∼965,000 reads carried Mu TIRs, demonstrating the specificity of this strategy. Among these TIRs, 21 novel Mu TIRs were discovered, revealing additional ...
Maize Inbreds Exhibit High Levels Of Copy Number Variation (Cnv) And Presence/Absence Variation (Pav) In Genome Content, 2019 University of Minnesota
Maize Inbreds Exhibit High Levels Of Copy Number Variation (Cnv) And Presence/Absence Variation (Pav) In Genome Content, Nathan M. Springer, Kai Ying, Yan Fu, Tieming Ji, Cheng-Ting Yeh, Yi Jia, Wei Wu, Todd Richmond, Jacob Kitzman, Heidi Rosenbaum, A. Leonardo Iniguez, W. Brad Barbazuk, Jeffrey A. Jeddeloh, Daniel S. Nettleton, Patrick S. Schnable
Following the domestication of maize over the past ∼10,000 years, breeders have exploited the extensive genetic diversity of this species to mold its phenotype to meet human needs. The extent of structural variation, including copy number variation (CNV) and presence/absence variation (PAV), which are thought to contribute to the extraordinary phenotypic diversity and plasticity of this important crop, have not been elucidated. Whole-genome, array-based, comparative genomic hybridization (CGH) revealed a level of structural diversity between the inbred lines B73 and Mo17 that is unprecedented among higher eukaryotes. A detailed analysis of altered segments of DNA conservatively estimates that ...
Flor Revisited (Again): Eqtl And Mutational Analysis Of Nb-Lrr Mediated Immunity To Powdery Mildew In Barley, 2019 United States Department of Agriculture
Flor Revisited (Again): Eqtl And Mutational Analysis Of Nb-Lrr Mediated Immunity To Powdery Mildew In Barley, Roger P. Wise, Priyanka Surana, Gregory S. Fuerst, Ruo Xu, Divya Mistry, Julie A. Dickerson, Dan Nettleton Dr.
Genes encoding early signaling events in pathogen defense often are identified only by their phenotype. Such genes involved in barley-powdery mildew interactions include Mla, specifying race-specific resistance; Rar1 (Required for Mla12-specified resistance1), and Rom1 (Restoration of Mla-specified resistance1). The HSP90-SGT1-RAR1 complex appears to function as chaperone in MLA-specified resistance, however, much remains to be discovered regarding the precise signaling underlying plant immunity. Genetic analyses of fast-neutron mutants derived from CI 16151 (Mla6) uncovered a novel locus, designated Rar3 (Required for Mla6-specified resistance3). Rar3 segregates independent of Mla6 and Rar1, and rar3 mutants are susceptible to Blumeria graminis f. sp. hordei ...
Crowdsourcing Image Analysis For Plant Phenomics To Generate Ground Truth Data For Machine Learning, 2019 Iowa State University
Crowdsourcing Image Analysis For Plant Phenomics To Generate Ground Truth Data For Machine Learning, Naihui Zhou, Zachary D. Siegel, Scott Zarecor, Nigel Lee, Darwin A. Campbell, Carson M. Andorf, Dan Nettleton, Carolyn J. Lawrence-Dill, Baskar Ganapathysubramanian, Jonathan W. Kelly, Iddo Friedberg
The accuracy of machine learning tasks critically depends on high quality ground truth data. Therefore, in many cases, producing good ground truth data typically involves trained professionals; however, this can be costly in time, effort, and money. Here we explore the use of crowdsourcing to generate a large number of training data of good quality. We explore an image analysis task involving the segmentation of corn tassels from images taken in a field setting. We investigate the accuracy, speed and other quality metrics when this task is performed by students for academic credit, Amazon MTurk workers, and Master Amazon MTurk ...
Differentially Expressed Genes In Blood From Young Pigs Between Two Swine Lines Divergently Selected For Feed Efficiency: Potential Biomarkers For Improving Feed Efficiency, 2019 Iowa State University
Differentially Expressed Genes In Blood From Young Pigs Between Two Swine Lines Divergently Selected For Feed Efficiency: Potential Biomarkers For Improving Feed Efficiency, Haibo Liu, Yet T. Nguyen, Daniel S. Nettleton, Jack C. M. Dekkers, Christopher K. Tuggle
The goal of this study was to find potential gene expression biomarkers in blood of piglets that can be used to predict pigs’ future feed efficiency. Using RNA-seq technology, we found 453 genes were differentially expressed (false discovery rate (FDR) ≤ 0.05) in the blood of two Yorkshire lines of pigs divergently selected for feed efficiency (FE) based on residual feed intake (RFI). Genes involved in several biosynthetic processes were overrepresented among genes more highly expressed in the low RFI line compared to the high RFI line. Weighted gene co-expression network analysis (WGCNA) also revealed genes involved in some of ...