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Characterization Of An N-Terminal Non-Core Domain Of Rag1 Gene Disrupted Syrian Hamster Model Generated By Crispr Cas9, Jinxin Miao, Baoling Ying, Rong Li, Ann E. Tollefson, Jacqueline F. Spencer, William S.M. Wold, Seok-Hwan Song, Il-Keun Kong, Karoly Toth, Yaohe Wang, Zhongde Wang 2018 Zhengzhou University

Characterization Of An N-Terminal Non-Core Domain Of Rag1 Gene Disrupted Syrian Hamster Model Generated By Crispr Cas9, Jinxin Miao, Baoling Ying, Rong Li, Ann E. Tollefson, Jacqueline F. Spencer, William S.M. Wold, Seok-Hwan Song, Il-Keun Kong, Karoly Toth, Yaohe Wang, Zhongde Wang

Animal, Dairy, and Veterinary Science Faculty Publications

The accumulating evidence demonstrates that Syrian hamsters have advantages as models for various diseases. To develop a Syrian hamster (Mesocricetus auratus) model of human immunodeficiency caused by RAG1 gene mutations, we employed the CRISPR/Cas9 system and introduced an 86-nucleotide frameshift deletion in the hamster RAG1 gene encoding part of the N-terminal non-core domain of RAG1. Histological and immunohistochemical analyses demonstrated that these hamsters (referred herein as RAG1-86nt hamsters) had atrophic spleen and thymus, and developed significantly less white pulp and were almost completely devoid of splenic lymphoid follicles. The RAG1-nt86 hamsters had barely detectable CD3+ and CD4+ T cells ...


Diversity, Structure And Sources Of Bacterial Communities In Earthworm Cocoons., Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez 2018 George Washington University

Diversity, Structure And Sources Of Bacterial Communities In Earthworm Cocoons., Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez

Computational Biology Institute

Animals start interactions with the bacteria that will constitute their microbiomes at embryonic stage. After mating, earthworms produce cocoons externally which will be colonized with bacteria from their parents and the environment. Due to the key role bacterial symbionts play on earthworm fitness, it is important to study bacterial colonization during cocoon formation. Here we describe the cocoon microbiome of the earthworms Eisenia andrei and E. fetida, which included 275 and 176 bacterial species, respectively. They were dominated by three vertically-transmitted symbionts, Microbacteriaceae, Verminephrobacter and Ca. Nephrothrix, which accounted for 88% and 66% of the sequences respectively. Verminephrobacter and Ca ...


Glucocorticoids Modulate Gastrointestinal Microbiome In A Wild Bird., José C Noguera, Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez, Alberto Velando 2018 George Washington University

Glucocorticoids Modulate Gastrointestinal Microbiome In A Wild Bird., José C Noguera, Manuel Aira, Marcos Pérez-Losada, Jorge Domínguez, Alberto Velando

Computational Biology Institute

It has recently been hypothesized that stress exposure (e.g. via glucocorticoid secretion) may dysregulate the bacterial gut microbiome, a crucial 'organ' in animal health. However, whether stress exposure (e.g. via glucocorticoid secretion) affects the bacterial gut microbiome of natural populations is unknown. We have experimentally altered the basal glucocorticoid level (corticosterone implants) in a wild avian species, the yellow-legged gull


Copy Number Variation In The Porcine Genome Detected From Whole-Genome Sequence, Rebecca Anderson 2018 University of Nebraska-Lincoln

Copy Number Variation In The Porcine Genome Detected From Whole-Genome Sequence, Rebecca Anderson

Honors Theses, University of Nebraska-Lincoln

Copy number variations (CNVs) are large insertions, deletions, and duplications in the genome that vary between individuals in a species. These variations are known to impact a broad range of phenotypes from molecular-level traits to higher-order clinical phenotypes. CNVs have been linked to complex traits in humans such as autism, attention deficit hyperactivity disorder, nervous system disorders, and early-onset extreme obesity. In this study, whole-genome sequence was obtained from 72 founders of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC) in Clay Center, Nebraska. This included 24 boars (12 Duroc and 12 Landrace ...


Atacseqqc: A Bioconductor Package For Post-Alignment Quality Assessment Of Atac-Seq Data, Jianhong Ou, Haibo Liu, Jun Yu, Michelle A. Kelliher, Lucio H. Castilla, Nathan D. Lawson, Lihua Julie Zhu 2018 Duke University

Atacseqqc: A Bioconductor Package For Post-Alignment Quality Assessment Of Atac-Seq Data, Jianhong Ou, Haibo Liu, Jun Yu, Michelle A. Kelliher, Lucio H. Castilla, Nathan D. Lawson, Lihua Julie Zhu

University of Massachusetts Medical School Faculty Publications

BACKGROUND: ATAC-seq (Assays for Transposase-Accessible Chromatin using sequencing) is a recently developed technique for genome-wide analysis of chromatin accessibility. Compared to earlier methods for assaying chromatin accessibility, ATAC-seq is faster and easier to perform, does not require cross-linking, has higher signal to noise ratio, and can be performed on small cell numbers. However, to ensure a successful ATAC-seq experiment, step-by-step quality assurance processes, including both wet lab quality control and in silico quality assessment, are essential. While several tools have been developed or adopted for assessing read quality, identifying nucleosome occupancy and accessible regions from ATAC-seq data, none of the ...


Seekdeep: Single-Base Resolution De Novo Clustering For Amplicon Deep Sequencing, Nicholas J. Hathaway, Christian M. Parobek, Jonathan J. Juliano, Jeffrey A. Bailey 2018 University of Massachusetts Medical School

Seekdeep: Single-Base Resolution De Novo Clustering For Amplicon Deep Sequencing, Nicholas J. Hathaway, Christian M. Parobek, Jonathan J. Juliano, Jeffrey A. Bailey

Open Access Articles

PCR amplicon deep sequencing continues to transform the investigation of genetic diversity in viral, bacterial, and eukaryotic populations. In eukaryotic populations such as Plasmodium falciparum infections, it is important to discriminate sequences differing by a single nucleotide polymorphism. In bacterial populations, single-base resolution can provide improved resolution towards species and strains. Here, we introduce the SeekDeep suite built around the qluster algorithm, which is capable of accurately building de novo clusters representing true, biological local haplotypes differing by just a single base. It outperforms current software, particularly at low frequencies and at low input read depths, whether resolving single-base differences ...


Identification Of Novel Genetic Variations For Amyotrophic Lateral Sclerosis (Als), Guang Xu 2018 University of Massachusetts Medical School

Identification Of Novel Genetic Variations For Amyotrophic Lateral Sclerosis (Als), Guang Xu

GSBS Dissertations and Theses

A list of genes have been identified to carry mutations causing familial ALS such as SOD1, TARDBP, C9orf72. But for sporadic ALS, which is 90% of all ALS cases, the underlying genetic variants are still largely unknown. There are multiple genome-wide association study (GWAS) for sporadic ALS, but usually a large number nominated SNP can hardly be replicated in larger cohort analysis. Also majority of GWAS SNP lie within noncoding region of genome, imposing a huge challenge to study their biological role in ALS pathology. With the rapid development of next-generation sequencing technology, we are able to sequence exome and ...


Evolution Of Extrema Features Reveals Optimal Stimuli For Biological State Transitions, Joshua TsuKang Chang, David Paydarfar 2018 University of Massachusetts Medical School Worcester

Evolution Of Extrema Features Reveals Optimal Stimuli For Biological State Transitions, Joshua Tsukang Chang, David Paydarfar

Open Access Articles

The ability to define the unique features of an input stimulus needed to control switch-like behavior in biological systems is an important problem in computational biology and medicine. We show in this study how highly complex and intractable optimization problems can be simplified by restricting the search to the signal's extrema as key feature points, and evolving the extrema features towards optimal solutions that closely match solutions derived from gradient-based methods. Our results suggest a model-independent approach for solving a class of optimization problems related to controlling switch-like state transitions.


Efficient Alignment Algorithms For Dna Sequencing Data, Nilesh Vinod Khiste 2018 The University of Western Ontario

Efficient Alignment Algorithms For Dna Sequencing Data, Nilesh Vinod Khiste

Electronic Thesis and Dissertation Repository

The DNA Next Generation Sequencing (NGS) technologies produce data at a low cost, enabling their application to many ambitious fields such as cancer research, disease control, personalized medicine etc. However, even after a decade of research, the modern aligners and assemblers are far from providing efficient and error free genome alignments and assemblies respectively. This is due to the inherent nature of the genome alignment and assembly problem, which involves many complexities. Many algorithms to address this problem have been proposed over the years, but there still is a huge scope for improvement in this research space.

Many new genome ...


The Genome Of The Hi5 Germ Cell Line From Trichoplusia Ni, An Agricultural Pest And Novel Model For Small Rna Biology, Yu Fu, Yujing Yang, Han Zhang, Gwen Farley, Junling Wang, Kaycee A. Quarles, Zhiping Weng, Phillip D. Zamore 2018 Boston University

The Genome Of The Hi5 Germ Cell Line From Trichoplusia Ni, An Agricultural Pest And Novel Model For Small Rna Biology, Yu Fu, Yujing Yang, Han Zhang, Gwen Farley, Junling Wang, Kaycee A. Quarles, Zhiping Weng, Phillip D. Zamore

Open Access Articles

We report a draft assembly of the genome of Hi5 cells from the lepidopteran insect pest, Trichoplusia ni, assigning 90.6% of bases to one of 28 chromosomes and predicting 14,037 protein-coding genes. Chemoreception and detoxification gene families reveal T. ni-specific gene expansions that may explain its widespread distribution and rapid adaptation to insecticides. Transcriptome and small RNA data from thorax, ovary, testis, and the germline-derived Hi5 cell line show distinct expression profiles for 295 microRNA- and > 393 piRNA-producing loci, as well as 39 genes encoding small RNA pathway proteins. Nearly all of the W chromosome is devoted to ...


Impact Of Concurrent Genomic Alterations Detected By Comprehensive Genomic Sequencing On Clinical Outcomes In East-Asian Patients With Egfr-Mutated Lung Adenocarcinoma, Seijiro Sato, Stephen Lyle, Toshifumi Wakai, Masanori Tsuchida 2018 Niigata University

Impact Of Concurrent Genomic Alterations Detected By Comprehensive Genomic Sequencing On Clinical Outcomes In East-Asian Patients With Egfr-Mutated Lung Adenocarcinoma, Seijiro Sato, Stephen Lyle, Toshifumi Wakai, Masanori Tsuchida

Open Access Articles

Next-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome. EGFR ...


A Systematic Approach To Rna-Associated Motif Discovery, Tian Gao, Jiang Shu, Juan Cui 2018 University of Nebraska-Lincoln

A Systematic Approach To Rna-Associated Motif Discovery, Tian Gao, Jiang Shu, Juan Cui

CSE Journal Articles

Background: Sequencing-based large screening of RNA-protein and RNA-RNA interactions has enabled the mechanistic study of post-transcriptional RNA processing and sorting, including exosome-mediated RNA secretion. The downstream analysis of RNA binding sites has encouraged the investigation of novel sequence motifs, which resulted in exceptional new challenges for identifying motifs from very short sequences (e.g., small non-coding RNAs or truncated messenger RNAs), where conventional methods tend to be ineffective. To address these challenges, we propose a novel motif-finding method and validate it on a wide range of RNA applications.

Results: We first perform motif analysis on microRNAs and longer RNA fragments ...


Novel Computational Methods For Sequencing Data Analysis: Mapping, Query, And Classification, Xinan Liu 2018 University of Kentucky

Novel Computational Methods For Sequencing Data Analysis: Mapping, Query, And Classification, Xinan Liu

Theses and Dissertations--Computer Science

Over the past decade, the evolution of next-generation sequencing technology has considerably advanced the genomics research. As a consequence, fast and accurate computational methods are needed for analyzing the large data in different applications. The research presented in this dissertation focuses on three areas: RNA-seq read mapping, large-scale data query, and metagenomics sequence classification.

A critical step of RNA-seq data analysis is to map the RNA-seq reads onto a reference genome. This dissertation presents a novel splice alignment tool, MapSplice3. It achieves high read alignment and base mapping yields and is able to detect splice junctions, gene fusions, and circular ...


Estimating The Heritability Of Thermal Tolerance In Acropora Cervicornis And The Physiological Basis Of Adaptation That Correlates To Survival At Elevated Temperatures, Kelsey L. Yetsko 2018 University of North Florida

Estimating The Heritability Of Thermal Tolerance In Acropora Cervicornis And The Physiological Basis Of Adaptation That Correlates To Survival At Elevated Temperatures, Kelsey L. Yetsko

UNF Graduate Theses and Dissertations

Human activities have substantially increased the atmospheric concentrations of greenhouse gases, resulting in warmer ocean temperatures that are having a negative impact on reef corals, which are highly susceptible to changes in temperature. Understanding the degree to which species vary in their tolerance to elevated temperatures and whether this variation is heritable is important in determining their ability to adapt to climate change. In order to address this, Acropora cervicornis fragments from 20 genetically distinct colonies were kept at either ambient or elevated temperatures, and mortality was monitored for 26 days. Heritability of thermal tolerance was estimated using a clonal ...


Streamlined Ex Vivo And In Vivo Genome Editing In Mouse Embryos Using Recombinant Adeno-Associated Viruses, Yeonsoo Yoon, Dan Wang, Phillip W. L. Tai, Joy Riley, Guangping Gao, Jaime A. Rivera-Perez 2018 University of Massachusetts Medical School

Streamlined Ex Vivo And In Vivo Genome Editing In Mouse Embryos Using Recombinant Adeno-Associated Viruses, Yeonsoo Yoon, Dan Wang, Phillip W. L. Tai, Joy Riley, Guangping Gao, Jaime A. Rivera-Perez

Pediatric Publications and Presentations

Recent advances using CRISPR-Cas9 approaches have dramatically enhanced the ease for genetic manipulation in rodents. Notwithstanding, the methods to deliver nucleic acids into pre-implantation embryos have hardly changed since the original description of mouse transgenesis more than 30 years ago. Here we report a novel strategy to generate genetically modified mice by transduction of CRISPR-Cas9 components into pre-implantation mouse embryos via recombinant adeno-associated viruses (rAAVs). Using this approach, we efficiently generated a variety of targeted mutations in explanted embryos, including indel events produced by non-homologous end joining and tailored mutations using homology-directed repair. We also achieved gene modification in vivo ...


Taming The Beast—A Community Teaching Material Resource For Beast 2, Joelle Barido-Sottani, Veronika Boskova, Louis du Plessis, Denise Kuhnert, Carsten Magnus, Venelin Mitov, Nicola F. Muller, Julia Pecerska, David A. Rasmussen, Chi Zhang, Alexei J. Drummond, Tracy A. Heath, Oliver G. Pybus, Timothy G. Vaughan, Tanja Stadler 2018 ETH Zurich

Taming The Beast—A Community Teaching Material Resource For Beast 2, Joelle Barido-Sottani, Veronika Boskova, Louis Du Plessis, Denise Kuhnert, Carsten Magnus, Venelin Mitov, Nicola F. Muller, Julia Pecerska, David A. Rasmussen, Chi Zhang, Alexei J. Drummond, Tracy A. Heath, Oliver G. Pybus, Timothy G. Vaughan, Tanja Stadler

Ecology, Evolution and Organismal Biology Publications

Phylogenetics and phylodynamics are central topics in modern evolutionary biology. Phylogenetic methods reconstruct the evolutionary relationships among organisms, whereas phylodynamic approaches reveal the underlying diversification processes that lead to the observed relationships. These two fields have many practical applications in disciplines as diverse as epidemiology, developmental biology, palaeontology, ecology, and linguistics. The combination of increasingly large genetic data sets and increases in computing power is facilitating the development of more sophisticated phylogenetic and phylodynamic methods. Big data sets allow us to answer complex questions. However, since the required analyses are highly specific to the particular data set and question, a ...


Benchmark Evaluation Of True Single Molecular Sequencing To Determine Cystic Fibrosis Airway Microbiome Diversity, Andrea Hahn, Matthew L. Bendall, Keylie M. Gibson, Hollis Chaney, Iman Sami, Geovanny F. Perez, Anastassios C. Koumbourlis, Timothy A. McCaffrey, Robert J. Freishtat, Keith A Crandall 2018 George Washington University

Benchmark Evaluation Of True Single Molecular Sequencing To Determine Cystic Fibrosis Airway Microbiome Diversity, Andrea Hahn, Matthew L. Bendall, Keylie M. Gibson, Hollis Chaney, Iman Sami, Geovanny F. Perez, Anastassios C. Koumbourlis, Timothy A. Mccaffrey, Robert J. Freishtat, Keith A Crandall

Computational Biology Institute

Cystic fibrosis (CF) is an autosomal recessive disease associated with recurrent lung infections that can lead to morbidity and mortality. The impact of antibiotics for treatment of acute pulmonary exacerbations on the CF airway microbiome remains unclear with prior studies giving conflicting results and being limited by their use of 16S ribosomal RNA sequencing. Our primary objective was to validate the use of true single molecular sequencing (tSMS) and PathoScope in the analysis of the CF airway microbiome. Three control samples were created with differing amounts of Burkholderia cepacia, Pseudomonas aeruginosa, and Prevotella melaninogenica, three common bacteria found in cystic ...


Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott 2018 Augustana College, Rock Island Illinois

Mrub_1325, Mrub_1326, Mrub_1327, And Mrub_1328 Are Orthologs Of B_3454, B_3455, B_3457, B_3458, Respectively Found In Escherichia Coli Coding For A Branched Chain Amino Acid Atp Binding Cassette (Abc) Transporter System, Bennett Tomlin, Adam Buric, Dr. Lori Scott

Meiothermus ruber Genome Analysis Project

In this project we investigated the biological function of the genes Mrub_1325, Mrub_1326, Mrub_1327, and Mrub_1328 (KEGG map number 02010). We predict these genes encode components of a Branched Chain Amino Acid ATP Binding Cassette (ABC) transporter: 1) Mrub_1325 (DNA coordinates 1357399-1358130 on the reverse strand) encodes the ATP binding domain; 2) Mrub_1326 (DNA coordinates 1358127-1359899 on the reverse strand) encodes the ATP-binding domain and permease domain; 3) Mrub_1327 (DNA coordinates 1359899-1360930 on the reverse strand) encodes a permease domain; and 4)Mrub_1328 (DNA coordinates 1711022-1712185 on the reverse strand) encodes the substrate binding domain. This system is not predicted ...


An Investigation Of Atomic Structures Derived From X-Ray Crystallography And Cryo-Electron Microscopy Using Distal Blocks Of Side-Chains, Lin Chen, Jing He, Salim Sazzed, Rayshawn Walker 2018 Old Dominion University

An Investigation Of Atomic Structures Derived From X-Ray Crystallography And Cryo-Electron Microscopy Using Distal Blocks Of Side-Chains, Lin Chen, Jing He, Salim Sazzed, Rayshawn Walker

Computer Science Faculty Publications

Cryo-electron microscopy (cryo-EM) is a structure determination method for large molecular complexes. As more and more atomic structures are determined using this technique, it is becoming possible to perform statistical characterization of side-chain conformations. Two data sets were involved to characterize block lengths for each of the 18 types of amino acids. One set contains 9131 structures resolved using X-ray crystallography from density maps with better than or equal to 1.5 Å resolutions, and the other contains 237 protein structures derived from cryo-EM density maps with 2-4 Å resolutions. The results show that the normalized probability density function of ...


Transcripity Split: Course-Based Rna-Seq Analysis Using The Ultrafast Kallisto-Sleuth Pipeline, Raymond A. Enke 2017 enkera@jmu.edu

Transcripity Split: Course-Based Rna-Seq Analysis Using The Ultrafast Kallisto-Sleuth Pipeline, Raymond A. Enke

Ray Enke Ph.D.

No abstract provided.


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