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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 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

Dan Nettleton

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, Swapnil S. Parhad, Tianxiong Yu, Gen Zhang, Nicholas P. Rice, Zhiping Weng, William E. Theurkauf 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, Kristin Abramo, Anne-Laure Valton, Sergey V. Venev, Hakan Ozadam, A. Nicole Fox, Job Dekker 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 2019 Iowa State University

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

Dan Nettleton

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, 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 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

Dan Nettleton

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, Roger P. Wise, Priyanka Surana, Gregory S. Fuerst, Ruo Xu, Divya Mistry, Julie A. Dickerson, Dan Nettleton Dr. 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.

Dan Nettleton

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, 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 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

Dan Nettleton

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, Haibo Liu, Yet T. Nguyen, Daniel S. Nettleton, Jack C. M. Dekkers, Christopher K. Tuggle 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

Dan Nettleton

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 ...


An In Silico Study Of G Protein-Coupled-Receptor Activation, Specifically In The Corticotropin Releasing Factor Receptor And The Glucagon-Like Peptide Receptor, Nicolas Angelo Scorese 2019 Rowan University

An In Silico Study Of G Protein-Coupled-Receptor Activation, Specifically In The Corticotropin Releasing Factor Receptor And The Glucagon-Like Peptide Receptor, Nicolas Angelo Scorese

Theses and Dissertations

The drug discovery process is an extremely long and expensive process that modern computational methods help to alleviate. Through the use of computational methods, we provide information and insight into the activation methods of class B GPCRs so that future drugs can be developed to have less side effects. The first study focuses on the corticotropin releasing factor receptor, which is a good drug target for anxiety and depression. A mechanism of activation was theorized which focuses less on molecular switches (as has been the focus of several papers) and more on large scale conformation at the intracellular region of ...


Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang 2019 University of Massachusetts Medical School

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang

Kurt Piepenbrink

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as ...


Barkbase: Epigenomic Annotation Of Canine Genomes, Kate Megquier, Xue Li, Kathleen Morrill, Brittney Logan, Elinor K. Karlsson 2019 Broad Institute of MIT and Harvard

Barkbase: Epigenomic Annotation Of Canine Genomes, Kate Megquier, Xue Li, Kathleen Morrill, Brittney Logan, Elinor K. Karlsson

Program in Molecular Medicine Publications and Presentations

Dogs are an unparalleled natural model for investigating the genetics of health and disease, particularly for complex diseases like cancer. Comprehensive genomic annotation of regulatory elements active in healthy canine tissues is crucial both for identifying candidate causal variants and for designing functional studies needed to translate genetic associations into disease insight. Currently, canine geneticists rely primarily on annotations of the human or mouse genome that have been remapped to dog, an approach that misses dog-specific features. Here, we describe BarkBase, a canine epigenomic resource available at barkbase.org. BarkBase hosts data for 27 adult tissue types, with biological replicates ...


In Silico Identification Of Genetic Mutations Conferring Resistance To Acetohydroxyacid Synthase Inhibitors: A Case Study Of Kochia Scoparia, Yan Li, Michael D. Netherland, Chaoyang Zhang, Huixiao Hong, Ping Gong 2019 Bennett Aerospace, Inc.

In Silico Identification Of Genetic Mutations Conferring Resistance To Acetohydroxyacid Synthase Inhibitors: A Case Study Of Kochia Scoparia, Yan Li, Michael D. Netherland, Chaoyang Zhang, Huixiao Hong, Ping Gong

Faculty Publications

Mutations that confer herbicide resistance are a primary concern for herbicide-based chemical control of invasive plants and are often under-characterized structurally and functionally. As the outcome of selection pressure, resistance mutations usually result from repeated long-term applications of herbicides with the same mode of action and are discovered through extensive field trials. Here we used acetohydroxyacid synthase (AHAS) of Kochia scoparia (KsAHAS) as an example to demonstrate that, given the sequence of a target protein, the impact of genetic mutations on ligand binding could be evaluated and resistance mutations could be identified using a biophysics-based computational approach. Briefly, the ...


Fusarium Euwallacea: A Serious Threat To The Native And Ornamental Trees And Shrubs In Southern California, Greg Tyler, Yixing Zheng, Michael Kulinich, Hagop Atamian 2019 Chapman University

Fusarium Euwallacea: A Serious Threat To The Native And Ornamental Trees And Shrubs In Southern California, Greg Tyler, Yixing Zheng, Michael Kulinich, Hagop Atamian

Student Scholar Symposium Abstracts and Posters

Fusarium Euwallacea is a fungus that has established symbiotic relationship with the beetle Euwallacea aff. fornicata. The beetle bores through the tree bark and into the sapwood making long tunnels inside the trees. The beetle carries the F. Euwallacea in a specialized structure on its body called mandibular mycangia and cultivates the fungus in the tunnels on which the beetle feeds to grow and reproduce. The growth of the fungus obstructs water and mineral transport in the plant xylem tissue, resulting in dieback, wilt and mortality of the host tree. Fungi are known to secrete proteins called effectors in the ...


Designing Computational Biology Workflows With Perl - Part 2, Esma Yildirim 2019 CUNY Queensborough Community College

Designing Computational Biology Workflows With Perl - Part 2, Esma Yildirim

Open Educational Resources

This material briefly reintroduces the DNA double Helix structure, explains SNP and INDEL mutations in genes and describes FASTA, FASTQ, BAM and VCF file formats. It also explains the index creation, alignment, sorting, marking duplicates and variant calling steps of a simple preprocessing workflow and how to write a Perl script to automate the execution of these steps on a Virtual Machine Image.


Designing Computational Biology Workflows With Perl - Part 1, Esma Yildirim 2019 CUNY Queensborough Community College

Designing Computational Biology Workflows With Perl - Part 1, Esma Yildirim

Open Educational Resources

This material introduces Linux File System structures and demonstrates how to use commands to communicate with the operating system through a Terminal program. Basic program structures and system() function of Perl are discussed. A brief introduction to gene-sequencing terminology and file formats are given.


Designing Computational Biology Workflows With Perl - Part 1, Esma Yildirim 2019 CUNY Queensborough Community College

Designing Computational Biology Workflows With Perl - Part 1, Esma Yildirim

Open Educational Resources

This material introduces the AWS console interface, describes how to create an instance on AWS with the VMI provided, connect to that machine instance using the SSH protocol. Once connected, it requires the students to write a script to enter the data folder, which includes gene-sequencing input files and print the first five line of each file remotely. The same exercise can be applied if the VMI is installed on a local machine using virtualization software (e.g. Oracle VirtualBox). In this case, the Terminal program of the VMI can be used to do the exercise.


Designing Computational Biology Workflows With Perl - Part 2, Esma Yildirim 2019 CUNY Queensborough Community College

Designing Computational Biology Workflows With Perl - Part 2, Esma Yildirim

Open Educational Resources

This material introduces the AWS console interface, describes how to create an instance on AWS with the VMI provided and connect to that machine instance using the SSH protocol. Once connected, it requires the students to write a script to automate the tasks to create VCF files from two different sample genomes belonging to E.coli microorganisms by using the FASTA and FASTQ files in the input folder of the virtual machine. The same exercise can be applied if the VMI is installed on a local machine using virtualization software (e.g. Oracle VirtualBox). In this case, the Terminal program ...


Designing Computational Biology Workflows With Perl - Part 1 & 2, Esma Yildirim 2019 CUNY Queensborough Community College

Designing Computational Biology Workflows With Perl - Part 1 & 2, Esma Yildirim

Open Educational Resources

This manual guides the instructor to combine the partial files of the virtual machine image and construct sequencer.ova file. It is accompanied by the partial files of the virtual machine image.


Surveying Apicomplexan Diversity And Dynamics In Narragansett Bay, Evelyn Spencer 2019 University of Rhode Island

Surveying Apicomplexan Diversity And Dynamics In Narragansett Bay, Evelyn Spencer

Senior Honors Projects

Parasites play an important role in marine ecosystems and their diversity is generally understudied. Apicomplexans, a group of parasitic protists in the phylum Alveolata, infect a wide variety of animal hosts and are abundant in ecosystems spanning from Polar Regions to Neotropical rainforests. Previous data generated from marine sediments in Antarctica, Naples Bay, and off the coast of Oslo, exhibit high diversity and numbers of apicomplexans. Abundance and diversity of these protists are unknown for Narragansett Bay, despite the fact that they infect many commercially important species. The aim of my study was to obtain abundance data and understand genetic ...


Computational Genomic Models For Spatio-Temporal Investigation Of Early Lung Cancer Pathology, Smruthy Sivakumar 2019 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Computational Genomic Models For Spatio-Temporal Investigation Of Early Lung Cancer Pathology, Smruthy Sivakumar

UT GSBS Dissertations and Theses (Open Access)

Lung cancer, of which non-small cell lung cancer (NSCLC) is the most common form, is the second most prevalent cancer and the leading cause of cancer-related deaths. NSCLCs primarily comprise adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC). Advances in early detection and prevention have been limited by the lack of early-stage biomarkers and targets. A comprehensive molecular characterization of premalignant lesions and tumor-adjacent normal tissue can aid in better understanding NSCLC pathogenesis. However, these investigations are further challenged by limited tissue availability and low cellular fractions of detectable somatic mutations.

Therefore, there is a dearth of knowledge about the pathogenesis ...


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