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1

Cancer gene discovery goes mobile.  

PubMed

A new study describes a tool, Lentihop, for somatic insertional mutagenesis in human cells and uses this system in combination with cancer genome data to define new genes and pathways involved in sarcoma development. Gene discovery in this way suggests that we are far from a complete catalog of cancer drivers. PMID:25162801

van der Weyden, Louise; Ranzani, Marco; Adams, David J

2014-09-01

2

Gene discovery in oral squamous cell carcinoma through the Head and Neck Cancer Genome Anatomy Project: confirmation by microarray analysis  

Microsoft Academic Search

The near completion of the human genome project and the recent development of novel, highly sensitive high-throughput techniques have now afforded the unique opportunity to perform a comprehensive molecular characterization of normal, precancerous, and malignant cells, including those derived from squamous carcinomas of the head and neck (HNSCC). As part of these efforts, representative cDNA libraries from patient sets, comprising

C Leethanakul; V Knezevic; V Patel; P Amornphimoltham; J Gillespie; E. J Shillitoe; P Emko; M. H Park; M. R Emmert-Buck; R. L Strausberg; D. B Krizman; J. S Gutkind

2003-01-01

3

Discovery Park Impact International Breast Cancer & Nutrition (IBCN) Project  

E-print Network

Discovery Park Impact International Breast Cancer & Nutrition (IBCN) Project NEED The development assistance with proposals, budgets, communication tools, and many details. RESOLUTION Discovery Park provides with other Purdue expertise. IMPACTS Discovery Park is the infrastructure supporting the creation of several

Holland, Jeffrey

4

Human brain evolution: From gene discovery to phenotype discovery  

PubMed Central

The rise of comparative genomics and related technologies has added important new dimensions to the study of human evolution. Our knowledge of the genes that underwent expression changes or were targets of positive selection in human evolution is rapidly increasing, as is our knowledge of gene duplications, translocations, and deletions. It is now clear that the genetic differences between humans and chimpanzees are far more extensive than previously thought; their genomes are not 98% or 99% identical. Despite the rapid growth in our understanding of the evolution of the human genome, our understanding of the relationship between genetic changes and phenotypic changes is tenuous. This is true even for the most intensively studied gene, FOXP2, which underwent positive selection in the human terminal lineage and is thought to have played an important role in the evolution of human speech and language. In part, the difficulty of connecting genes to phenotypes reflects our generally poor knowledge of human phenotypic specializations, as well as the difficulty of interpreting the consequences of genetic changes in species that are not amenable to invasive research. On the positive side, investigations of FOXP2, along with genomewide surveys of gene-expression changes and selection-driven sequence changes, offer the opportunity for “phenotype discovery,” providing clues to human phenotypic specializations that were previously unsuspected. What is more, at least some of the specializations that have been proposed are amenable to testing with noninvasive experimental techniques appropriate for the study of humans and apes. PMID:22723367

Preuss, Todd M.

2012-01-01

5

GeneEd: Genetics, Education, Discovery  

NSDL National Science Digital Library

The GeneEd website was created by the National Library of Medicine (NLM), the National Human Genome Research Institute (NHGRI), and the National Institutes of Health (NIH) as a helpful resource for the teaching and learning of genetics. On the site, visitors can find labs and experiments, fact sheets, and teacher resources on topics including DNA forensics, genetic conditions, evolution, and biostatistics. First-time visitors will want to start their journey by looking over the Topics tab at the top of the page. There are 40 different thematic areas here consisting of articles, video clips, webcasts, and links to additional quality resources vetted by the GeneEd web team. The Labs & Experiments section includes virtual labs that explore the genetics of different organisms as well as links to resources provided by the Howard Hughes Medical Institute and Cold Spring Harbor Laboratory. Young people may also wish to take a look at the Careers in Genetics section as it features interviews with scientists that will inspire and delight.

6

Biomarker Discovery Using Statistically Significant Gene Sets  

PubMed Central

Abstract Analysis of large gene expression data sets in the presence and absence of a phenotype can lead to the selection of a group of genes serving as biomarkers jointly predicting the phenotype. Among gene selection methods, filter methods derived from ranked individual genes have been widely used in existing products for diagnosis and prognosis. Univariate filter approaches selecting genes individually, although computationally efficient, often ignore gene interactions inherent in the biological data. On the other hand, multivariate approaches selecting gene subsets are known to have a higher risk of selecting spurious gene subsets due to the overfitting of the vast number of gene subsets evaluated. Here we propose a framework of statistical significance tests for multivariate feature selection that can reduce the risk of selecting spurious gene subsets. Using three existing data sets, we show that our proposed approach is an essential step to identify such a gene set that is generated by a significant interaction of its members, even improving classification performance when compared to established approaches. This technique can be applied for the discovery of robust biomarkers for medical diagnosis. PMID:21457009

Kim, Hoon; Watkinson, John

2011-01-01

7

Project Discovery: College Option Orientation Program. FIPSE Final Report.  

ERIC Educational Resources Information Center

Project Discovery is a community-based educational intervention program for low income and minority students. It operates outside the traditional public education system. The following projects comprise the program: (1) Project Discovery for ninth to eleventh graders, which is a College Option Orientation program; and (2) Discovery Groups for…

Total Action Against Poverty, Inc., Roanoke, VA.

8

Cancer gene discovery: exploiting insertional mutagenesis.  

PubMed

Insertional mutagenesis has been used as a functional forward genetics screen for the identification of novel genes involved in the pathogenesis of human cancers. Different insertional mutagens have been successfully used to reveal new cancer genes. For example, retroviruses are integrating viruses with the capacity to induce the deregulation of genes in the neighborhood of the insertion site. Retroviruses have been used for more than 30 years to identify cancer genes in the hematopoietic system and mammary gland. Similarly, another tool that has revolutionized cancer gene discovery is the cut-and-paste transposons. These DNA elements have been engineered to contain strong promoters and stop cassettes that may function to perturb gene expression upon integration proximal to genes. In addition, complex mouse models characterized by tissue-restricted activity of transposons have been developed to identify oncogenes and tumor suppressor genes that control the development of a wide range of solid tumor types, extending beyond those tissues accessible using retrovirus-based approaches. Most recently, lentiviral vectors have appeared on the scene for use in cancer gene screens. Lentiviral vectors are replication-defective integrating vectors that have the advantage of being able to infect nondividing cells, in a wide range of cell types and tissues. In this review, we describe the various insertional mutagens focusing on their advantages/limitations, and we discuss the new and promising tools that will improve the insertional mutagenesis screens of the future. PMID:23928056

Ranzani, Marco; Annunziato, Stefano; Adams, David J; Montini, Eugenio

2013-10-01

9

CARTaGENE Project  

Cancer.gov

Launched in October 2009, the CARTaGENE project is the largest prospective longitudinal cohort of Québec. CARTaGENE's distinguishing features are that it is a quantitative prospective cohort that has deeply phenotyped 20,000 individuals aged 40-69, the age most individuals will develop chronic disease. 37,000 individuals will be enrolled by 2014. It is an open-access infrastructure enabling researchers to investigate the genetic, environmental, and lifestyle determinants of disease in the French Canadian population. CARTaGENE has collected whole blood for DNA from 30,000 individuals.

10

Genome-enabled Discovery of Carbon Sequestration Genes  

SciTech Connect

The fate of carbon below ground is likely to be a major factor determining the success of carbon sequestration strategies involving plants. Despite their importance, molecular processes controlling belowground C allocation and partitioning are poorly understood. This project is leveraging the Populus trichocarpa genome sequence to discover genes important to C sequestration in plants and soils. The focus is on the identification of genes that provide key control points for the flow and chemical transformations of carbon in roots, concentrating on genes that control the synthesis of chemical forms of carbon that result in slower turnover rates of soil organic matter (i.e., increased recalcitrance). We propose to enhance carbon allocation and partitioning to roots by 1) modifying the auxin signaling pathway, and the invertase family, which controls sucrose metabolism, and by 2) increasing root proliferation through transgenesis with genes known to control fine root proliferation (e.g., ANT), 3) increasing the production of recalcitrant C metabolites by identifying genes controlling secondary C metabolism by a major mQTL-based gene discovery effort, and 4) increasing aboveground productivity by enhancing drought tolerance to achieve maximum C sequestration. This broad, integrated approach is aimed at ultimately enhancing root biomass as well as root detritus longevity, providing the best prospects for significant enhancement of belowground C sequestration.

Tuskan, Gerald A [ORNL] [ORNL; Tschaplinski, Timothy J [ORNL] [ORNL; Kalluri, Udaya C [ORNL] [ORNL; Yin, Tongming [ORNL] [ORNL; Yang, Xiaohan [ORNL] [ORNL; Zhang, Xinye [ORNL] [ORNL; Engle, Nancy L [ORNL] [ORNL; Ranjan, Priya [ORNL] [ORNL; Basu, Manojit M [ORNL] [ORNL; Gunter, Lee E [ORNL] [ORNL; Jawdy, Sara [ORNL] [ORNL; Martin, Madhavi Z [ORNL] [ORNL; Campbell, Alina S [ORNL] [ORNL; DiFazio, Stephen P [ORNL] [ORNL; Davis, John M [University of Florida] [University of Florida; Hinchee, Maud [ORNL] [ORNL; Pinnacchio, Christa [U.S. Department of Energy, Joint Genome Institute] [U.S. Department of Energy, Joint Genome Institute; Meilan, R [Purdue University] [Purdue University; Busov, V. [Michigan Technological University] [Michigan Technological University; Strauss, S [Oregon State University] [Oregon State University

2009-01-01

11

Our Water World 4-H Marine Science Discovery Project  

E-print Network

Our Water World 4-H Marine Science Discovery Project Leader Guide OREGON STATE UNIVERSITY EXTENSION Catch 36 Amazing Marine Mammal Trivia 39 Vanishing Habitat 44 A Voyage Through Your Home and Supermarket

Tullos, Desiree

12

Gene Expression Imputation Techniques for Robust Post Genomic Knowledge Discovery  

Microsoft Academic Search

Microarrays measure expression patterns of thousands of genes at a time, under same or diverse conditions, to facilitate faster\\u000a analysis of biological processes. This gene expression data is being widely used for diagnosis, prognosis and tailored drug\\u000a discovery. Microarray data, however, commonly contains missing values, which can have high impact on subsequent biological\\u000a knowledge discovery methods. This has been catalyst

Muhammad Shoaib B. Sehgal; Iqbal Gondal; Laurence Dooley

2008-01-01

13

Gene-based SNP discovery as part of the Japanese Millennium Genome Project: identification of 190 562 genetic variations in the human genome  

Microsoft Academic Search

.   To construct an infrastructure for genome-wide association studies of common diseases or drug sensitivities, we have been\\u000a systematically exploring common variants by resequencing genomic regions containing genes in DNA from 24 Japanese individuals.\\u000a We have analyzed a total of 154 Mb, corresponding to approximately 5% of the human genome, and so far have identified 174\\u000a 269 single-nucleotide polymorphisms and

Hisanori Haga; Ryo Yamada; Yozo Ohnishi; Yusuke Nakamura; Toshihiro Tanaka; Yusuke Nakamura

2002-01-01

14

Discovery of Tumor Suppressor Gene Function.  

ERIC Educational Resources Information Center

This is an update of a 1991 review on tumor suppressor genes written at a time when understanding of how the genes work was limited. A recent major breakthrough in the understanding of the function of tumor suppressor genes is discussed. (LZ)

Oppenheimer, Steven B.

1995-01-01

15

GenePath: An Intelligent Assistant to the Discovery of Genetic Pathways  

NSDL National Science Digital Library

The Baylor College of Medicine in Houston and the University of Ljubljana in Slovenia present an improved, second version of GenePath, a "web-enabled intelligent assistant for the analysis of genetic data and for discovery of genetic networks." GenePath automates the complex process of determining gene interrelationships and users may download existing projects or start new ones from scratch. The website also provides a very detailed, nicely-designed guide to running GenePath, available as a separate downloadable document.

16

GWATCH: a web platform for automated gene association discovery analysis  

PubMed Central

Background As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations. Findings Here we present a dynamic web-based platform – GWATCH – that automates and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene association search and discovery analysis of large genome-wide datasets; 2) Expanded visual display of gene associations for genome-wide variants (SNPs, indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region, and a dynamic genome browser illustrating gene association chromosomal regions; 3) Real-time validation/replication of candidate or putative genes suggested from other sources, limiting Bonferroni genome-wide association study (GWAS) penalties; 4) Open data release and sharing by eliminating privacy constraints (The National Human Genome Research Institute (NHGRI) Institutional Review Board (IRB), informed consent, The Health Insurance Portability and Accountability Act (HIPAA) of 1996 etc.) on unabridged results, which allows for open access comparative and meta-analysis. Conclusions GWATCH is suitable for both GWAS and whole genome sequence association datasets. We illustrate the utility of GWATCH with three large genome-wide association studies for HIV-AIDS resistance genes screened in large multicenter cohorts; however, association datasets from any study can be uploaded and analyzed by GWATCH. PMID:25374661

2014-01-01

17

Class Discovery in Gene Expression Data Amir Ben-Dor  

E-print Network

Class Discovery in Gene Expression Data Amir Ben-Dor Agilent Laboratories and University of Washington amirbd@cs.washington.edu Nir Friedman Hebrew University nir@cs.huji.ac.il Zohar Yakhini Agilent Laboratories and Technion zohary@labs.agilent.com ABSTRACT Recent studies (Alizadeh et al, [1]; Bittner et al

Friedman, Nir

18

Class Discovery in Gene Expression Data Amir BenDor  

E-print Network

Class Discovery in Gene Expression Data Amir Ben­Dor Agilent Laboratories and University Agilent Laboratories and Technion zohary@labs.agilent.com ABSTRACT Recent studies (Alizadeh et al, [1 automatic analysis methods. Our approach is based on statistically scoring candidate partitions according

Friedman, Nir

19

A Discovery Laboratory Investigating Bacterial Gene Regulation  

NSDL National Science Digital Library

This laboratory exercise introduces students to experimental design and gene regulation using different sugar ("food" sources) and an enzyme assay for beta-glalctosidase to identify different E. coli stains with respect to lac operon mutations, then designing their own experiments to study the various aspects of the lac operon.

Robert Moss (Wofford College;)

1999-01-01

20

Novel venom gene discovery in the platypus  

Microsoft Academic Search

ABSTRACT: BACKGROUND: To date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components. RESULTS: We identified 83 novel putative platypus venom genes from

Camilla M Whittington; Anthony T Papenfuss; Devin P Locke; Elaine R Mardis; Richard K Wilson; Sahar Abubucker; Makedonka Mitreva; Emily SW Wong; Arthur L Hsu; Philip W Kuchel; Katherine Belov; Wesley C Warren

2010-01-01

21

Gene discovery and the genetic basis of calcium consumption  

PubMed Central

This review makes the case that gene discovery is a worthwhile approach to the study of ingestive behavior in general and to calcium appetite in particular. A description of the methods used to discover genes is provided for non-geneticists. Areas covered include the characterization of an appropriate phenotype, the choice of suitable mouse strains, the generation of a hybrid cross, interval mapping, congenic strain production, and candidate gene analysis. The approach is illustrated with an example involving mice of the C57BL/6J and PWK/PhJ strains, which differ in avidity for calcium solutions. The variation between the strains can be attributed to at least seven quantitative trait loci (QTLs). One of these QTLs is most likely accounted for by Tas1r3, which is a gene involved in the detection of sweet and umami tastes. The discovery of a novel function for a gene with no previously known role in calcium consumption illustrates the power of gene discovery methods to uncover novel mechanisms. PMID:18499198

Tordoff, Michael G.

2008-01-01

22

Technology development for gene discovery and full-length sequencing  

SciTech Connect

In previous years, with support from the U.S. Department of Energy, we developed methods for construction of normalized and subtracted cDNA libraries, and constructed hundreds of high-quality libraries for production of Expressed Sequence Tags (ESTs). Our clones were made widely available to the scientific community through the IMAGE Consortium, and millions of ESTs were produced from our libraries either by collaborators or by our own sequencing laboratory at the University of Iowa. During this grant period, we focused on (1) the development of a method for preferential cloning of tissue-specific and/or rare transcripts, (2) its utilization to expedite EST-based gene discovery for the NIH Mouse Brain Molecular Anatomy Project, (3) further development and optimization of a method for construction of full-length-enriched cDNA libraries, and (4) modification of a plasmid vector to maximize efficiency of full-length cDNA sequencing by the transposon-mediated approach. It is noteworthy that the technology developed for preferential cloning of rare mRNAs enabled identification of over 2,000 mouse transcripts differentially expressed in the hippocampus. In addition, the method that we optimized for construction of full-length-enriched cDNA libraries was successfully utilized for the production of approximately fifty libraries from the developing mouse nervous system, from which over 2,500 full-ORF-containing cDNAs have been identified and accurately sequenced in their entirety either by our group or by the NIH-Mammalian Gene Collection Program Sequencing Team.

Marcelo Bento Soares

2004-07-19

23

Integrated analysis of gene expression by association rules discovery  

PubMed Central

Background Microarray technology is generating huge amounts of data about the expression level of thousands of genes, or even whole genomes, across different experimental conditions. To extract biological knowledge, and to fully understand such datasets, it is essential to include external biological information about genes and gene products to the analysis of expression data. However, most of the current approaches to analyze microarray datasets are mainly focused on the analysis of experimental data, and external biological information is incorporated as a posterior process. Results In this study we present a method for the integrative analysis of microarray data based on the Association Rules Discovery data mining technique. The approach integrates gene annotations and expression data to discover intrinsic associations among both data sources based on co-occurrence patterns. We applied the proposed methodology to the analysis of gene expression datasets in which genes were annotated with metabolic pathways, transcriptional regulators and Gene Ontology categories. Automatically extracted associations revealed significant relationships among these gene attributes and expression patterns, where many of them are clearly supported by recently reported work. Conclusion The integration of external biological information and gene expression data can provide insights about the biological processes associated to gene expression programs. In this paper we show that the proposed methodology is able to integrate multiple gene annotations and expression data in the same analytic framework and extract meaningful associations among heterogeneous sources of data. An implementation of the method is included in the Engene software package. PMID:16464256

Carmona-Saez, Pedro; Chagoyen, Monica; Rodriguez, Andres; Trelles, Oswaldo; Carazo, Jose M; Pascual-Montano, Alberto

2006-01-01

24

Novel venom gene discovery in the platypus  

PubMed Central

Background To date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components. Results We identified 83 novel putative platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of platypus envenomation. Conclusions This study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom. PMID:20920228

2010-01-01

25

Genome-wide Approaches for Cancer Gene Discovery  

PubMed Central

One of the central aims of cancer research is to identify and characterize cancer-causing alterations in cancer genomes. In recent years, unprecedented advances in genome-wide sequencing, functional genomics technologies of RNA interference screens and methods to evaluate three-dimensional chromatin organization in vivo have resulted in important discoveries regarding human cancer. The cancer causing genes identified from these new genome-wide technologies have also provided opportunities for effective and personalized cancer therapy. In this review, we describe some of the most recent technologies for cancer gene discovery. We also provide specific examples where these technologies have proven remarkably successful in uncovering important cancer-causing alterations. PMID:21757246

Lizardi, Paul M.; Forloni, Matteo; Wajapeyee, Narendra

2011-01-01

26

Gene Discovery and Product Development for Grain Quality Traits  

NSDL National Science Digital Library

The composition of oils, proteins, and carbohydrates in seeds of corn, soybean, and other crops has been modified to produce grains with enhanced value. Both plant breeding and molecular technologies have been used to produce plants carrying the desired traits. Genomics-based strategies for gene discovery, coupled with high-throughput transformation processes and miniaturized, automated analytical and functionality assays, have accelerated the identification of product candidates. Molecular markerâÂÂbased breeding strategies have been used to accelerate the process of moving trait genes into high-yielding germplasm for commercialization. These products are being tested for applications in food, feed, and industrial markets.

Barbara Mazur (DuPont Agricultural Products Experimental Station;); Enno Krebers (DuPont Agricultural Products Experimental Station;); Scott Tingey (DuPont Agricultural Products Experimental Station;)

1999-07-16

27

Gene discovery and product development for grain quality traits.  

PubMed

The composition of oils, proteins, and carbohydrates in seeds of corn, soybean, and other crops has been modified to produce grains with enhanced value. Both plant breeding and molecular technologies have been used to produce plants carrying the desired traits. Genomics-based strategies for gene discovery, coupled with high-throughput transformation processes and miniaturized, automated analytical and functionality assays, have accelerated the identification of product candidates. Molecular marker-based breeding strategies have been used to accelerate the process of moving trait genes into high-yielding germplasm for commercialization. These products are being tested for applications in food, feed, and industrial markets. PMID:10411493

Mazur, B; Krebbers, E; Tingey, S

1999-07-16

28

Future Mission Proposal Opportunities: Discovery, New Frontiers, and Project Prometheus  

NASA Technical Reports Server (NTRS)

The NASA Office of Space Science is expanding opportunities to propose missions to comets, asteroids, and other solar system targets. The Discovery Program continues to be popular, with two sample return missions, Stardust and Genesis, currently in operation. The New Frontiers Program, a new proposal opportunity modeled on the successful Discovery Program, begins this year with the release of its first Announcement of Opportunity. Project Prometheus, a program to develop nuclear electric power and propulsion technology intended to enable a new class of high-power, high-capability investigations, is a third opportunity to propose solar system exploration. All three classes of mission include a commitment to provide data to the Planetary Data System, any samples to the NASA Curatorial Facility at Johnson Space Center, and programs for education and public outreach.

Niebur, S. M.; Morgan, T. H.; Niebur, C. S.

2003-01-01

29

The Discovery and Application of Gene Fusions in Prostate Cancer  

PubMed Central

Chromosomal rearrangements play a causal role in hematological and mesenchymal malignancies. Importantly, the resulting gene fusions can serve as specific therapeutic targets, as exemplified by the development of imatinib (Gleevec), which specifically inhibits the BCR-ABL gene fusion product that defines chronic myeloid leukemia. Recently, gene fusions involving the prostate specific gene TMPRSS2 and members of the ETS family of transcription factors were identified in the majority of PSA-screened prostate cancers. In this review, we summarize the identification, characterization and detection of TMPRSS2:ETS gene fusions and their role in prostate cancer development. We also discuss the discovery of additional 5? partners that define distinct classes of ETS gene fusions based on the prostate specificity and androgen responsiveness of the 5? partner. Additionally, we also summarize conflicting reports about associations between gene fusion status and patient outcome. The specificity of ETS gene fusions in prostate cancer suggests that they may have causal roles in prostate cancer and suggest utility in prostate cancer detection, stratification and treatment. PMID:18422767

Morris, David S.; Tomlins, Scott A.; Montie, James E.; Chinnaiyan, Arul M.

2009-01-01

30

Discovery of a widely distributed toxin biosynthetic gene cluster  

PubMed Central

Bacteriocins represent a large family of ribosomally produced peptide antibiotics. Here we describe the discovery of a widely conserved biosynthetic gene cluster for the synthesis of thiazole and oxazole heterocycles on ribosomally produced peptides. These clusters encode a toxin precursor and all necessary proteins for toxin maturation and export. Using the toxin precursor peptide and heterocycle-forming synthetase proteins from the human pathogen Streptococcus pyogenes, we demonstrate the in vitro reconstitution of streptolysin S activity. We provide evidence that the synthetase enzymes, as predicted from our bioinformatics analysis, introduce heterocycles onto precursor peptides, thereby providing molecular insight into the chemical structure of streptolysin S. Furthermore, our studies reveal that the synthetase exhibits relaxed substrate specificity and modifies toxin precursors from both related and distant species. Given our findings, it is likely that the discovery of similar peptidic toxins will rapidly expand to existing and emerging genomes. PMID:18375757

Lee, Shaun W.; Mitchell, Douglas A.; Markley, Andrew L.; Hensler, Mary E.; Gonzalez, David; Wohlrab, Aaron; Dorrestein, Pieter C.; Nizet, Victor; Dixon, Jack E.

2008-01-01

31

Kevin Burgess' Research: Project 3 Rapid Discovery Of Catalysts Optimization For  

E-print Network

Kevin Burgess' Research: Project 3 Rapid Discovery Of Catalysts Optimization has been targeted, then discovery of catalysts to mediate those transformations tends to be a slow transformations for organic syntheses. B. Research Strategies Significance We have used the catalyst shown

Burgess, Kevin

32

Discovery of 100-Plus Genes Tied to Autism May Improve Treatments  

MedlinePLUS

... page, please enable JavaScript. Discovery of 100-Plus Genes Tied to Autism May Improve Treatments Disorder has ... 29, 2014 Related MedlinePlus Pages Autism Spectrum Disorder Genes and Gene Therapy WEDNESDAY, Oct. 29, 2014 (HealthDay ...

33

DiscoverySchool.com : Your Genes, Your Future  

NSDL National Science Digital Library

DiscoverSchool.com offers a lesson plan for 6-8th graders based on a Discovery Channel program Your Genes, Your Future. The lesson plan focuses on healthy behaviors rather than genetics as such, although some of the extension activities deal with genetics more directly. Students will review the benefits of eating well, exercising, and other healthy behaviors, as well as discuss the dangers of drugs, smoking, etc. Provided Web links will help students with in-class research, and educators will find useful teaching tools for creating worksheets, quizzes, and subject-specific puzzles.

2007-12-12

34

Boolean Property Encoding for Local Set Pattern Discovery: An Application to Gene  

E-print Network

pattern (e.g., association rules, closed sets) discovery techniques from boolean matrices that encode geneBoolean Property Encoding for Local Set Pattern Discovery: An Application to Gene Expression Data the most from local set pattern mining approaches, a needed step concerns gene expression property encoding

Boulicaut, Jean-François

35

The ROTSE Supernova Verification Project (RSVP): Status and Early Discoveries  

NASA Astrophysics Data System (ADS)

The goal of the ROTSE Supernova Verification Project is the discovery of nearby supernova shortly after shock breakout followed by multi-epoch spectral observations as the lightcurves evolve. The very early spectra effectively constrain the progenitor properties and explosion models, but only a few such observations exist for SN Ia. The sequence of spectral observations reveals deeper and deeper layers of the explosion over time that can be used to construct a detailed picture of the burning process. This program follows the concept of the Texas Supernova Search initiated and executed successfully by Robert Quimby using ROTSE-IIIb at McDonald Observatory. To enlarge the discovery rate, we have developed image subtraction code to be installed on all four ROTSE-III telescopes. By monitoring selected fields nightly to a typical limiting magnitude of 18.5, ROTSE-III is able to discover a nearby supernova earlier than many similar searches. The expected discovery rate is 3 per month at one dedicated site. Since August 2007, our pipeline has been fully operational on ROTSE-IIIb and has discovered 5 supernovae, 3 of which we reported as ATELs and CBETs while the remaining two were found concurrently and reported by others. Among these, SN 2007if is a particularly interesting example of an apparent SN Ia involving the destruction of a super-Chandrasekhar mass system. Its spectrum closely matches that of SN 2003fg which was the first such case that has been observed. Our photometry data show a lightcurve that is a factor of 2 overluminous for a SN Ia, consistent with this interpretation. This work has been supported by NASA grants NNG-04WC41G and NNX-07AF02G.

Yuan, Fang; Akerlof, C.; Quimby, R.; Aretakis, J.; McKay, T.; Miller, J. M.; Rykoff, E. S.; Swan, H. F.; Wheeler, J. C.

2007-12-01

36

Genome Enabled Discovery of Carbon Sequestration Genes in Poplar  

SciTech Connect

The goals of the S.H. Strauss laboratory portion of 'Genome-enabled discovery of carbon sequestration genes in poplar' are (1) to explore the functions of candidate genes using Populus transformation by inserting genes provided by Oakridge National Laboratory (ORNL) and the University of Florida (UF) into poplar; (2) to expand the poplar transformation toolkit by developing transformation methods for important genotypes; and (3) to allow induced expression, and efficient gene suppression, in roots and other tissues. As part of the transformation improvement effort, OSU developed transformation protocols for Populus trichocarpa 'Nisqually-1' clone and an early flowering P. alba clone, 6K10. Complete descriptions of the transformation systems were published (Ma et. al. 2004, Meilan et. al 2004). Twenty-one 'Nisqually-1' and 622 6K10 transgenic plants were generated. To identify root predominant promoters, a set of three promoters were tested for their tissue-specific expression patterns in poplar and in Arabidopsis as a model system. A novel gene, ET304, was identified by analyzing a collection of poplar enhancer trap lines generated at OSU (Filichkin et. al 2006a, 2006b). Other promoters include the pGgMT1 root-predominant promoter from Casuarina glauca and the pAtPIN2 promoter from Arabidopsis root specific PIN2 gene. OSU tested two induction systems, alcohol- and estrogen-inducible, in multiple poplar transgenics. Ethanol proved to be the more efficient when tested in tissue culture and greenhouse conditions. Two estrogen-inducible systems were evaluated in transgenic Populus, neither of which functioned reliably in tissue culture conditions. GATEWAY-compatible plant binary vectors were designed to compare the silencing efficiency of homologous (direct) RNAi vs. heterologous (transitive) RNAi inverted repeats. A set of genes was targeted for post transcriptional silencing in the model Arabidopsis system; these include the floral meristem identity gene (APETALA1 or AP1), auxin response factor gene (ETTIN), the gene encoding transcriptional factor of WD40 family (TRANSPARENTTESTAGLABRA1 or TTG1), and the auxin efflux carrier (PIN-FORMED2 or PIN2) gene. More than 220 transgenic lines of the 1st, 2nd and 3rd generations were analyzed for RNAi suppression phenotypes (Filichkin et. al., manuscript submitted). A total of 108 constructs were supplied by ORNL, UF and OSU and used to generate over 1,881 PCR verified transgenic Populus and over 300 PCR verified transgenic Arabidopsis events. The Populus transgenics alone required Agrobacterium co-cultivations of 124.406 explants.

Filichkin, Sergei; Etherington, Elizabeth; Ma, Caiping; Strauss, Steve

2007-02-22

37

Gene expression endophenotypes: a novel approach for gene discovery in Alzheimer's disease  

PubMed Central

Uncovering the underlying genetic component of any disease is key to the understanding of its pathophysiology and may open new avenues for development of therapeutic strategies and biomarkers. In the past several years, there has been an explosion of genome-wide association studies (GWAS) resulting in the discovery of novel candidate genes conferring risk for complex diseases, including neurodegenerative diseases. Despite this success, there still remains a substantial genetic component for many complex traits and conditions that is unexplained by the GWAS findings. Additionally, in many cases, the mechanism of action of the newly discovered disease risk variants is not inherently obvious. Furthermore, a genetic region with multiple genes may be identified via GWAS, making it difficult to discern the true disease risk gene. Several alternative approaches are proposed to overcome these potential shortcomings of GWAS, including the use of quantitative, biologically relevant phenotypes. Gene expression levels represent an important class of endophenotypes. Genetic linkage and association studies that utilize gene expression levels as endophenotypes determined that the expression levels of many genes are under genetic influence. This led to the postulate that there may exist many genetic variants that confer disease risk via modifying gene expression levels. Results from the handful of genetic studies which assess gene expression level endophenotypes in conjunction with disease risk suggest that this combined phenotype approach may both increase the power for gene discovery and lead to an enhanced understanding of their mode of action. This review summarizes the evidence in support of gene expression levels as promising endophenotypes in the discovery and characterization of novel candidate genes for complex diseases, which may also represent a novel approach in the genetic studies of Alzheimer's and other neurodegenerative diseases. PMID:21569597

2011-01-01

38

Amyotrophic Lateral Sclerosis: An Emerging Era of Collaborative Gene Discovery  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms (SNPs) that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples (such as DNA), phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS. PMID:18060051

Gwinn, Katrina; Corriveau, Roderick A.; Mitsumoto, Hiroshi; Bednarz, Kate; Brown, Robert H.; Cudkowicz, Merit; Gordon, Paul H.; Hardy, John; Kasarskis, Edward J.; Kaufmann, Petra; Miller, Robert; Sorenson, Eric; Tandan, Rup; Traynor, Bryan J.; Nash, Josefina; Sherman, Alex; Mailman, Matthew D.; Ostell, James; Bruijn, Lucie; Cwik, Valerie; Rich, Stephen S.; Singleton, Andrew; Refolo, Larry; Andrews, Jaime; Zhang, Ran; Conwit, Robin; Keller, Margaret A.

2007-01-01

39

Sequencing of GJB2 in Cameroonians and Black South Africans and comparison to 1000 Genomes Project Data Support Need to Revise Strategy for Discovery of Nonsyndromic Deafness Genes in Africans.  

PubMed

Abstract Mutations in the GJB2 gene, encoding connexin 26, could account for 50% of congenital, nonsyndromic, recessive deafness cases in some Caucasian/Asian populations. There is a scarcity of published data in sub-Saharan Africans. We Sanger sequenced the coding region of the GJB2 gene in 205 Cameroonian and Xhosa South Africans with congenital, nonsyndromic deafness; and performed bioinformatic analysis of variations in the GJB2 gene, incorporating data from the 1000 Genomes Project. Amongst Cameroonian patients, 26.1% were familial. The majority of patients (70%) suffered from sensorineural hearing loss. Ten GJB2 genetic variants were detected by sequencing. A previously reported pathogenic mutation, g.3741_3743delTTC (p.F142del), and a putative pathogenic mutation, g.3816G>A (p.V167M), were identified in single heterozygous samples. Amongst eight the remaining variants, two novel variants, g.3318-41G>A and g.3332G>A, were reported. There were no statistically significant differences in allele frequencies between cases and controls. Principal Components Analyses differentiated between Africans, Asians, and Europeans, but only explained 40% of the variation. The present study is the first to compare African GJB2 sequences with the data from the 1000 Genomes Project and have revealed the low variation between population groups. This finding has emphasized the hypothesis that the prevalence of mutations in GJB2 in nonsyndromic deafness amongst European and Asian populations is due to founder effects arising after these individuals migrated out of Africa, and not to a putative "protective" variant in the genomic structure of GJB2 in Africans. Our results confirm that mutations in GJB2 are not associated with nonsyndromic deafness in Africans. PMID:25162826

Bosch, Jason; Noubiap, Jean Jacques N; Dandara, Collet; Makubalo, Nomlindo; Wright, Galen; Entfellner, Jean-Baka Domelevo; Tiffin, Nicki; Wonkam, Ambroise

2014-11-01

40

Canonical Correlation Analysis for Gene-Based Pleiotropy Discovery  

PubMed Central

Genome-wide association studies have identified a wealth of genetic variants involved in complex traits and multifactorial diseases. There is now considerable interest in testing variants for association with multiple phenotypes (pleiotropy) and for testing multiple variants for association with a single phenotype (gene-based association tests). Such approaches can increase statistical power by combining evidence for association over multiple phenotypes or genetic variants respectively. Canonical Correlation Analysis (CCA) measures the correlation between two sets of multidimensional variables, and thus offers the potential to combine these two approaches. To apply CCA, we must restrict the number of attributes relative to the number of samples. Hence we consider modules of genetic variation that can comprise a gene, a pathway or another biologically relevant grouping, and/or a set of phenotypes. In order to do this, we use an attribute selection strategy based on a binary genetic algorithm. Applied to a UK-based prospective cohort study of 4286 women (the British Women's Heart and Health Study), we find improved statistical power in the detection of previously reported genetic associations, and identify a number of novel pleiotropic associations between genetic variants and phenotypes. New discoveries include gene-based association of NSF with triglyceride levels and several genes (ACSM3, ERI2, IL18RAP, IL23RAP and NRG1) with left ventricular hypertrophy phenotypes. In multiple-phenotype analyses we find association of NRG1 with left ventricular hypertrophy phenotypes, fibrinogen and urea and pleiotropic relationships of F7 and F10 with Factor VII, Factor IX and cholesterol levels. PMID:25329069

Seoane, Jose A.; Campbell, Colin; Day, Ian N. M.; Casas, Juan P.; Gaunt, Tom R.

2014-01-01

41

Canonical correlation analysis for gene-based pleiotropy discovery.  

PubMed

Genome-wide association studies have identified a wealth of genetic variants involved in complex traits and multifactorial diseases. There is now considerable interest in testing variants for association with multiple phenotypes (pleiotropy) and for testing multiple variants for association with a single phenotype (gene-based association tests). Such approaches can increase statistical power by combining evidence for association over multiple phenotypes or genetic variants respectively. Canonical Correlation Analysis (CCA) measures the correlation between two sets of multidimensional variables, and thus offers the potential to combine these two approaches. To apply CCA, we must restrict the number of attributes relative to the number of samples. Hence we consider modules of genetic variation that can comprise a gene, a pathway or another biologically relevant grouping, and/or a set of phenotypes. In order to do this, we use an attribute selection strategy based on a binary genetic algorithm. Applied to a UK-based prospective cohort study of 4286 women (the British Women's Heart and Health Study), we find improved statistical power in the detection of previously reported genetic associations, and identify a number of novel pleiotropic associations between genetic variants and phenotypes. New discoveries include gene-based association of NSF with triglyceride levels and several genes (ACSM3, ERI2, IL18RAP, IL23RAP and NRG1) with left ventricular hypertrophy phenotypes. In multiple-phenotype analyses we find association of NRG1 with left ventricular hypertrophy phenotypes, fibrinogen and urea and pleiotropic relationships of F7 and F10 with Factor VII, Factor IX and cholesterol levels. PMID:25329069

Seoane, Jose A; Campbell, Colin; Day, Ian N M; Casas, Juan P; Gaunt, Tom R

2014-10-01

42

A New Omics Data Resource of Pleurocybellaporrigens for Gene Discovery  

PubMed Central

Background Pleurocybellaporrigens is a mushroom-forming fungus, which has been consumed as a traditional food in Japan. In 2004, 55 people were poisoned by eating the mushroom and 17 people among them died of acute encephalopathy. Since then, the Japanese government has been alerting Japanese people to take precautions against eating the P. porrigens mushroom. Unfortunately, despite efforts, the molecular mechanism of the encephalopathy remains elusive. The genome and transcriptome sequence data of P. porrigens and the related species, however, are not stored in the public database. To gain the omics data in P. porrigens, we sequenced genome and transcriptome of its fruiting bodies and mycelia by next generation sequencing. Methodology/Principal Findings Short read sequences of genomic DNAs and mRNAs in P. porrigens were generated by Illumina Genome Analyzer. Genome short reads were de novo assembled into scaffolds using Velvet. Comparisons of genome signatures among Agaricales showed that P. porrigens has a unique genome signature. Transcriptome sequences were assembled into contigs (unigenes). Biological functions of unigenes were predicted by Gene Ontology and KEGG pathway analyses. The majority of unigenes would be novel genes without significant counterparts in the public omics databases. Conclusions Functional analyses of unigenes present the existence of numerous novel genes in the basidiomycetes division. The results mean that the omics information such as genome, transcriptome and metabolome in basidiomycetes is short in the current databases. The large-scale omics information on P. porrigens, provided from this research, will give a new data resource for gene discovery in basidiomycetes. PMID:23936076

Dohra, Hideo; Someya, Takumi; Takano, Tomoyuki; Harada, Kiyonori; Omae, Saori; Hirai, Hirofumi; Yano, Kentaro; Kawagishi, Hirokazu

2013-01-01

43

Discovery and New Frontiers Project Budget Analysis Tool  

NASA Technical Reports Server (NTRS)

The Discovery and New Frontiers (D&NF) programs are multi-project, uncoupled programs that currently comprise 13 missions in phases A through F. The ability to fly frequent science missions to explore the solar system is the primary measure of program success. The program office uses a Budget Analysis Tool to perform "what-if" analyses and compare mission scenarios to the current program budget, and rapidly forecast the programs ability to meet their launch rate requirements. The tool allows the user to specify the total mission cost (fixed year), mission development and operations profile by phase (percent total mission cost and duration), launch vehicle, and launch date for multiple missions. The tool automatically applies inflation and rolls up the total program costs (in real year dollars) for comparison against available program budget. Thus, the tool allows the user to rapidly and easily explore a variety of launch rates and analyze the effect of changes in future mission or launch vehicle costs, the differing development profiles or operational durations of a future mission, or a replan of a current mission on the overall program budget. Because the tool also reports average monthly costs for the specified mission profile, the development or operations cost profile can easily be validate against program experience for similar missions. While specifically designed for predicting overall program budgets for programs that develop and operate multiple missions concurrently, the basic concept of the tool (rolling up multiple, independently-budget lines) could easily be adapted to other applications.

Newhouse, Marilyn E.

2011-01-01

44

Chromosome substitution strains: gene discovery functional analysis and systems studies  

PubMed Central

Laboratory mice are valuable in biomedical research in part because of the extraordinary diversity of genetic resources that are available for studies of complex genetic traits and as models for human biology and disease. Chromosome substitution strains (CSSs) are important in this resource portfolio because of their demonstrated use for gene discovery, genetic and epigenetic studies, functional characterizations, and systems analysis. CSSs are made by replacing a single chromosome in a host strain with the corresponding chromosome from a donor strain. A complete CSS panel involves a total of 22 engineered inbred strains, one for each of the 19 autosomes, one each for the X and Y chromosomes, and one for mitochondria. A genome survey simply involves comparing each phenotype for each of the CSSs with the phenotypes of the host strain. The CSS panels that are available for laboratory mice have been used to dissect a remarkable variety of phenotypes and to characterize an impressive array of disease models. These surveys have revealed considerable phenotypic diversity even among closely related progenitor strains, evidence for strong epistasis and for heritable epigenetic changes. Perhaps most importantly, and presumably because of their unique genetic constitution, CSSs, and congenic strains derived from them, the genetic variants underlying quantitative trait loci (QTLs) are readily identified and functionally characterized. Together these studies show that CSSs are important resource for laboratory mice. PMID:22961226

Nadeau, Joseph H.; Forejt, Jiri; Takada, Toyoyuki; Shiroishi, Toshihiko

2014-01-01

45

The discovery of the microphthalmia locus and its gene, Mitf  

PubMed Central

Summary The history of the discovery of the microphthalmia locus and its gene, now called Mitf, is a testament to the triumph of serendipity. Although the first microphthalmia mutation was discovered among the descendants of a mouse that was irradiated for the purpose of mutagenesis, the mutation most likely was not radiation-induced but occurred spontaneously in one of the parents of a later breeding. Although Mitf might eventually have been identified by other molecular genetic techniques, it was first cloned from a chance transgene insertion at the microphthalmia locus. And although Mitf was found to encode a member of a well-known transcription factor family, its analysis might still be in its infancy had Mitf not turned out to be of crucial importance for the physiology and pathology of many distinct organs, including eye, ear, immune system, bone, and skin, and in particular for melanoma. In fact, near seven decades of Mitf research have led to many insights about development, function, degeneration, and malignancies of a number of specific cell types, and it is hoped that these insights will one day lead to therapies benefitting those afflicted with diseases originating in these cell types. PMID:20807369

Arnheiter, Heinz

2010-01-01

46

Using Osteoclast Differentiation as a Model for Gene Discovery in an Undergraduate Cell Biology Laboratory  

PubMed Central

A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. The current article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory providing students, within a framework of bone cell biology, with a modern approach to gene discovery. Students are introduced to the topics of bone cells, bone synthesis, bone resorption, and osteoporosis. They then review the theory of microchip gene arrays, and study microchip array data generated during the differentiation of bone-resorbing osteoclasts in vitro. The class selects genes whose expression increases during osteoclastogenesis, and researches them in small groups using web-based bioinformatics tools. Students then go to a biotechnology company website to find and order siRNAs designed to “knockdown” expression of the gene of interest. Students then learn to transfect these siRNAs into osteoclasts, stimulate the cells to differentiate, assay osteoclast differentiation in vitro, and measure specific gene expression using real-time PCR and immunoblotting. Specific siRNA knockdown resulting in a decrease in osteoclastogenesis is indicative of a gene's physiological relevance. The results are analyzed statistically, and presented to the class in groups. In the past two years, students identified several genes essential for optimal osteoclast differentiation, including Myo1d. The students hypothesize that the myo1d protein functions in osteoclasts to deliver important proteins to the cell surface via vesicular transport along microfilaments. Student response to the new course was overwhelmingly positive. PMID:21567867

Picco, Jenna; Clements, Meghan; Witwicka, Hanna; Yang, Meiheng; Hoey, Margaret T.; Odgren, Paul R.

2014-01-01

47

Identifying splits with clear separation: a new class discovery method for gene expression data  

Microsoft Academic Search

We present a new class discovery method for microarray gene expression data. Based on a collection of gene ex- pression profiles from different tissue samples, the method searches for binary class distinctions in the set of sam- ples that show clear separation in the expression levels of specific subsets of genes. Several mutually independent class distinctions may be found, which

Anja Von Heydebreck; Wolfgang Huber; Annemarie Poustka; Martin Vingron

2001-01-01

48

Abstract--We present new results from Computational Neurogenetic Modeling to aid discoveries of complex gene  

E-print Network

of gene regulatory network. Solid (dashed) lines denote positive (negative) interactions between genes for the discovery of unknown interactions between genes in relation to their impact on brain activity. I Institute (KEDRI), Auckland University of Technology, Auckland, New Zealand (e- mail: {swysoski, nkasabov

Benuskova, Luba

49

Physics Discoveries  

NSDL National Science Digital Library

The Physics Discoveries section of the National Science Foundation (NSF) website brings together a "panoply of discoveries and innovations that began with NSF support." Indeed, it is quite a panoply and visitors will enjoy scrolling through the dozens of resources presented here. The projects profiled include new gene sequencing, celebrations of Marie Curie's birthday, space turbulence studies, and quantum computing. Each of these resources includes a press release, video coverage related to each project, and a set of additional websites. Visitors can also print out relevant materials and share these links via a range of social media tools.

50

Identifying differentially expressed genes using false discovery rate controlling procedures  

Microsoft Academic Search

Motivation: DNA microarrays have recently been used for the purpose of monitoring expression levels of thousands of genes simultaneously and identifying those genes that are differentially expressed. The probability that a false identification (type I error) is committed can increase sharply when the number of tested genes gets large. Correlation between the test statistics attributed to gene co-regulation and dependency

Anat Reiner; Daniel Yekutieli; Yoav Benjamini

2003-01-01

51

De novo discovery of a tissue-specific gene regulatory module in a chordate  

E-print Network

De novo discovery of a tissue-specific gene regulatory module in a chordate David S. Johnson,1 Qing genes in the chordate, Ciona savignyi. Three independent types of data we generate contribute constructs assayed in the ascidian chordate, Ciona (Corbo et al. 1997; Johnson et al. 2004). The culmination

Sidow, Arend

52

A rank sum test method for informative gene discovery  

Microsoft Academic Search

Finding informative genes from microarray data is an important research problem in bioinformatics research and applications. Most of the existing methods rank features according to their discriminative capability and then find a subset of discriminative genes (usually top k genes). In particular, t-statistic criterion and its variants have been adopted extensively. This kind of methods rely on the statistics principle

Lin Deng; Jian Pei; Jinwen Ma; Dik Lun Lee

2004-01-01

53

A Rank Sum Test Method for Informative Gene Discovery  

Microsoft Academic Search

Finding informative genes from microarray data is an impor- tant research problem in bioinformatics research and appli- cations. Most of the existing methods rank features accord- ing to their discriminative capability and then flnd a subset of discriminative genes (usually top k genes). In particu- lar, t-statistic criterion and its variants have been adopted extensively. This kind of methods rely

Lin Deng; Jian Pei; Jinwen M; Dik Lun Lee

54

Gene sequencing project identifies abnormal gene that launches rare childhood leukemia  

Cancer.gov

Research led by the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project has identified a fusion gene responsible for almost 30 percent of a rare subtype of childhood leukemia with an extremely poor prognosis. The finding offers the first evidence of a mistake that gives rise to a significant percentage of acute megakaryoblastic leukemia (AMKL) cases in children. AMKL accounts for about 10 percent of pediatric acute myeloid leukemia (AML). The discovery paves the way for desperately needed treatment advances.

55

Using the DFCI Gene Index Databases for Biological Discovery  

PubMed Central

The DFCI Gene Index Web pages provide access to analyses of ESTs and gene sequences for nearly 114 species, as well as a number of resources derived from these. Each species-specific database is presented using a common format with a home page. A variety of methods exist that allow users to search each species-specific database. Methods implemented currently include nucleotide or protein sequence queries using WU-BLAST, text-based searches using various sequence identifiers, searches by gene, tissue and library name, and searches using functional classes through Gene Ontology assignments. This protocol provides guidance for using the Gene Index Databases to extract information. PMID:20205187

Antonescu, Corina; Antonescu, Valentin; Sultana, Razvan; Quackenbush, John

2014-01-01

56

New Discoveries From The Archean Biosphere Drilling Project (ABDP)  

Microsoft Academic Search

The Archean Biosphere Drilling Project (ABDP), an international scientific drilling project involving scientists from the USA, Australia and Japan, was initiated in Pilbara Craton, Western Australia. The scientific objectives of the ABDP are the identification of microfossils and biomarkers, the clarification of geochemical environment of the early Earth, and the understanding of geophysical contribution to the co-evolution of life and

M. Nedachi

2004-01-01

57

Molecular classification of cancer: {C}lass discovery and class prediction by gene expression monitoring  

Microsoft Academic Search

Although cancer classiÞcation has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery)or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classiÞcation based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case.A class discovery

Todd R. Golub; Donna K. Slonim; Pablo Tamayo; C. Huard; M. Gaasenbeek; Jill P. Mesirov; H. Coller; Mignon L. Loh; James R. Downing; M. A. Caligiuri; C. D. Bloomfield; Eric S. Lander

1999-01-01

58

Computational method for discovery of estrogen responsive genes  

PubMed Central

Estrogen has a profound impact on human physiology and affects numerous genes. The classical estrogen reaction is mediated by its receptors (ERs), which bind to the estrogen response elements (EREs) in target gene's promoter region. Due to tedious and expensive experiments, a limited number of human genes are functionally well characterized. It is still unclear how many and which human genes respond to estrogen treatment. We propose a simple, economic, yet effective computational method to predict a subclass of estrogen responsive genes. Our method relies on the similarity of ERE frames across different promoters in the human genome. Matching ERE frames of a test set of 60 known estrogen responsive genes to the collection of over 18?000 human promoters, we obtained 604 candidate genes. Evaluating our result by comparison with the published microarray data and literature, we found that more than half (53.6%, 324/604) of predicted candidate genes are responsive to estrogen. We believe this method can significantly reduce the number of testing potential estrogen target genes and provide functional clues for annotating part of genes that lack functional information. PMID:15576347

Tang, Suisheng; Tan, Sin Lam; Ramadoss, Suresh Kumar; Kumar, Arun Prashanth; Tang, Man-Hung Eric; Bajic, Vladimir B.

2004-01-01

59

Gene discovery and prevalence in inherited retinal dystrophies.  

PubMed

Inherited retinal dystrophies are Mendelian neurodegenerative conditions classified as pigmentary retinopathies, macular dystrophies and others. Over a 21-year period, from 1990 to 2011, we have screened in Montpellier 107 genes in 609 families and have identified a causal mutation in 68.5% of them. Following a gene candidate approach, we established that RPE65, the isomerohydrolase of the visual cycle, is responsible for severe childhood blindness (Leber congenital amaurosis or early onset retinal dystrophy). In an ongoing study, we screened the genes in a series of 283 families with dominant retinitis pigmentosa and we have estimated that 80% of the families have a mutation in a known gene. A similar study is currently undergoing for autosomal recessive retinitis pigmentosa. Finally, we have identified IMPG1 as a responsible gene for rare cases of macular vitelliform dystrophy with a dominant or recessive inheritance. PMID:24702842

Hamel, Christian P

2014-03-01

60

Discovery Learning and Cognitive Development--The UKU Project.  

ERIC Educational Resources Information Center

Prompted by pupil dissatisfaction and indifference, an experimental scheme of modified working routines involving approximately 500 pupils and 40 teachers was conducted in senior level classes in the Municipality of Ockero between 1976 and 1981. The purpose of the project was to transform the everyday life of school and to devise methods for…

Marklund, Inger, Ed.

1985-01-01

61

Computational discovery of gene modules, regulatory networks and expression programs  

E-print Network

High-throughput molecular data are revolutionizing biology by providing massive amounts of information about gene expression and regulation. Such information is applicable both to furthering our understanding of fundamental ...

Gerber, Georg Kurt, 1970-

2007-01-01

62

A spelt-specific ?-gliadin gene: discovery and detection  

Microsoft Academic Search

Polymerase chain reaction (PCR) primers GAG5 and GAG6 were designed based on published ?-gliadin gene sequences and applied\\u000a to 35 cultivars of closely related spelt (Triticum spelta L.) and hexaploid wheat (T. aestivum L.). Eight tetraploid durum wheat (T. durum Desf.) cultivars were included in the analysis. The obtained PCR products originated from two ?-gliadin genes which were\\u000a mapped to

M. von Büren; J. Lüthy; P. Hübner

2000-01-01

63

Immune gene discovery in the crucian carp Carassius auratus.  

PubMed

The crucian carp Carassius auratus (Cyprinidae) is one of the important fish species in aquaculture. Although the crucian carp has several economic benefits, their immune system and gene information have not been investigated in depth as yet. Here, we performed the transcriptome analysis of C. auratus using the pyrosequencing method and selected several immune-related genes. Of unigenes obtained in this species, we identified a number of immune system-related genes (e.g. adhesive protein, antimicrobial protein, apoptosis- and cell cycle-related protein, cellular defense effector, immune regulator, pattern recognition protein, protease, protease inhibitor, reduction/oxidation-related protein, signal transduction-related protein and stress protein) that are potentially useful for studies on fish immunity. To be of public and practical use, we designed primer pairs of each gene from the crucian carp for real-time RT-PCR application and tested the amplicon identity of entire gene sets with the total RNA sample. For comparative analysis, we measured tissue-preferential transcript profiles of selected genes. This study will be helpful to extend our knowledge on the immune system of the crucian carp in comparative aspects and to develop the crucian carp as a potential model organism for aquatic quality monitoring in fish farming. PMID:24287371

Rhee, Jae-Sung; Jeong, Chang-Bum; Kim, Duck-Hyun; Kim, Il-Chan; Lee, Yong Sung; Lee, Chulwoo; Lee, Jae-Seong

2014-01-01

64

GENOME-ENABLED DISCOVERY OF CARBON SEQUESTRATION GENES IN POPLAR  

SciTech Connect

Plants utilize carbon by partitioning the reduced carbon obtained through photosynthesis into different compartments and into different chemistries within a cell and subsequently allocating such carbon to sink tissues throughout the plant. Since the phytohormones auxin and cytokinin are known to influence sink strength in tissues such as roots (Skoog & Miller 1957, Nordstrom et al. 2004), we hypothesized that altering the expression of genes that regulate auxin-mediated (e.g., AUX/IAA or ARF transcription factors) or cytokinin-mediated (e.g., RR transcription factors) control of root growth and development would impact carbon allocation and partitioning belowground (Fig. 1 - Renewal Proposal). Specifically, the ARF, AUX/IAA and RR transcription factor gene families mediate the effects of the growth regulators auxin and cytokinin on cell expansion, cell division and differentiation into root primordia. Invertases (IVR), whose transcript abundance is enhanced by both auxin and cytokinin, are critical components of carbon movement and therefore of carbon allocation. Thus, we initiated comparative genomic studies to identify the AUX/IAA, ARF, RR and IVR gene families in the Populus genome that could impact carbon allocation and partitioning. Bioinformatics searches using Arabidopsis gene sequences as queries identified regions with high degrees of sequence similarities in the Populus genome. These Populus sequences formed the basis of our transgenic experiments. Transgenic modification of gene expression involving members of these gene families was hypothesized to have profound effects on carbon allocation and partitioning.

DAVIS J M

2007-10-11

65

Systematic Discovery of New Genes in the Saccharomyces cerevisiae Genome  

PubMed Central

We used genome-wide comparative analysis of predicted protein sequences to identify many novel small genes, named smORFs for small open reading frames, within the budding yeast genome. Further analysis of 117 of these new genes showed that 84 are transcribed. We extended our analysis of one smORF conserved from yeast to human. This investigation provides an updated and comprehensive annotation of the yeast genome, validates additional concepts in the study of genomes in silico, and increases the expected numbers of coding sequences in a genome with the corresponding impact on future functional genomics and proteomics studies. PMID:12566404

Kessler, Marco M.; Zeng, Qiandong; Hogan, Sarah; Cook, Robin; Morales, Arturo J.; Cottarel, Guillaume

2003-01-01

66

Methods in comparative genomics: genome correspondence, gene identification and motif discovery  

E-print Network

1 Methods in comparative genomics: genome correspondence, gene identification and motif discovery@mit.edu, nickp@genome.wi.mit.edu, bwb@genome.wi.mit.edu, bab@mit.edu, lander@wi.mit.edu (1) MIT/Whitehead Institute Center for Genome Research, 320 Charles St., Cambridge MA 02139 (2) MIT Computer Science

Kellis, Manolis

67

Edinburgh Research Explorer High-throughput gene discovery in the rat  

E-print Network

, Rhoads, B, Schaefer, K, Smith, C, Sunjevaric, I, Trout, K, Wu, N, Birkett, CL, Bischof, J, Gackle, B, VC & Soares, MB 2004, 'High-throughput gene discovery in the rat' Genome Research, vol 14, no. 4, pp to publication record in Edinburgh Research Explorer Published In: Genome Research General rights Copyright

MacDonald, Andrew

68

Motif Discovery Through Predictive Modeling of Gene Regulation  

Microsoft Academic Search

We present MEDUSA, an integrative method for learning motif models of tran- scription factor binding sites by incorporating promoter s equence and gene expres- sion data. We use a modern large-margin machine learning approach, based on boosting, to enable feature selection from the high-dimensional search space of candidate binding sequences while avoiding overfitting. At each iteration of the algorithm, MEDUSA

Manuel Middendorf; Anshul Kundaje; Mihir Shah; Yoav Freund; Chris H. Wiggins; Christina S. Leslie

2005-01-01

69

Discovery of SNPs in the swine nerve growth factor gene.  

PubMed

This study was aimed to search genetic variants for the swine nerve growth factor gene that associated with regulation of proliferation and differentiation of nervous systems. The swine nerve growth factor gene was screened with 5 primer sets for random populations of crossbred pigs born 2005-2007 at National Institute of Animal Science (NIAS). To verify genetic variants of miniature pigs, a total of 288,000 BAC clones generated from NIAS in 2007 were used. The selection of primer sequences was based on sequences of the swine in GenBank (L31898), and genetic variants have been discovered in the crossbred population positioned at 381 (A/C), 412 (C/T), 422 (G/A), 468 (G/C), 496 (A/G), 538 (T/C), 540 (G/A), and 547 (A/G) showing substitutions of amino acids. The identified sequences of miniature pigs including SNPs were submitted into GenBank with an accession number (GQ423508). The sequence alignment conducted to compare genetic distances between species, revealing not many high similarities between swine and human as approximately 0.89 that was a little bit high value than expected. Consequently, we suggest that the identified SNPs of the swine NGF gene may be used in the future to identify genetic markers in coding regions, regarding explanations of phenotypic variations. PMID:20182804

Chung, H Y; Kim, J Y

2010-10-01

70

Representative distance: a new similarity measure for class discovery from gene expression data.  

PubMed

Similarity measurement is one of the most important stages in the process of cancer discovery from gene expression data. Traditional distance functions, such as the Euclidean distance, the correlation coefficient measure, the cosine distance, and so on, are selected to quantify the similarity between two cancer samples. However, these measures do not take into account the properties of cancer samples and do not consider the relationships among the genes in gene expression data. In order to explore the properties of cancer samples and the relationships among genes, we design a new similarity measure called representative distance (RD) to identify cancer samples in gene expression data. Specifically, RD does not compute the distance between two cancer samples using all the genes, but only calculates the similarity using representative genes selected by the affinity propagation algorithm. Then, a similarity matrix is constructed based on the representative distance. Finally, the spectral clustering algorithm is adopted to partition the similarity matrix, and discover the biological meaningful samples. To our knowledge, this is the first time in which the representative distance is applied to class discovery for gene expression data. Experiments on real cancer datasets indicate that our similarity measure can i) outperform most of the traditional distance measures, ii) identify cancer samples correctly in most of the datasets. PMID:22893451

Yu, Zhiwen; You, Jane; Li, Le; Wong, Hau-San; Han, Guoqiang

2012-12-01

71

Sleeping Beauty mutagenesis: exploiting forward genetic screens for cancer gene discovery.  

PubMed

Sleeping Beauty (SB) is a powerful insertional mutagen used in somatic forward genetic screens to identify novel candidate cancer genes. In the past two years, SB has become widely adopted to model human pancreatic, hepatocellular, colorectal and neurological cancers to identify loci that participate in tumor initiation, progression and metastasis. Oncogenomic approaches have directly linked hundreds of genes identified by SB with human cancers, many with prognostic implications. These SB candidate cancer genes are aiding to prioritize punitive human cancer genes for follow-up studies and as possible biomarkers or therapeutic targets. This review highlights recent advances in SB cancer gene discovery, approaches to validate candidate cancer genes, and efforts to integrate SB data across all tumor types to prioritize drug development and tumor specificity. PMID:24657532

Mann, Michael B; Jenkins, Nancy A; Copeland, Neal G; Mann, Karen M

2014-02-01

72

Discovery and Functional Characterization of Recurrent Gene Fusions from 4,932 Primary Tumor Transcriptomes Across 19 Human Cancers - Chai Bandlamudi, TCGA Scientific Symposium 2014  

Cancer.gov

Home News and Events Multimedia Library Videos Discovery and Functional Characterization of Recurrent Gene Fusions from 4,932 Primary Tumor Transcr Discovery and Functional Characterization of Recurrent Gene Fusions from 4,932 Primary Tumor Transcriptomes

73

Manic-depression genes and the new millennium: poised for discovery  

Microsoft Academic Search

Manic-depressive illness is a common psychiatric disorder with complex etiology that likely involves multiple genes and non-genetic influences. The uncertain path to gene discovery has spurred considerable debate over genetic findings and gene-finding strategies. In this article, I review the main findings, with a focus on: (1) putative linked loci on chromosomes 1q31–32, 4p16, 6pter–p24, 10p14, 10q21–26, 12q23–24, 13q31–32, 18p11,

M Baron

2002-01-01

74

Scientific Discovery with the Blue Gene/L  

SciTech Connect

This project succeeded in developing key software optimization tools to bring fundamental QCD calculations of nucleon structure from the Terascale era through the Petascale era and prepare for the Exascale era. It also enabled fundamental QCD physics calculations and demonstrated the power of placing small versions of frontier emerging architectures at MIT to attract outstanding students to computational science. MIT also hosted a workshop September 19 2008 to brainstorm ways to promote computational science at top tier research universities and attract gifted students into the field, some of whom would provide the next generation of talent at our defense laboratories.

Negele, John W.

2011-12-09

75

Cohesin gene mutations in tumorigenesis: from discovery to clinical significance.  

PubMed

Cohesin is a multi-protein complex composed of four core subunits (SMC1A, SMC3, RAD21, and either STAG1 or STAG2) that is responsible for the cohesion of sister chromatids following DNA replication until its cleavage during mitosis thereby enabling faithful segregation of sister chromatids into two daughter cells. Recent cancer genomics analyses have discovered a high frequency of somatic mutations in the genes encoding the core cohesin subunits as well as cohesin regulatory factors (e.g. NIPBL, PDS5B, ESPL1) in a select subset of human tumors including glioblastoma, Ewing sarcoma, urothelial carcinoma, acute myeloid leukemia, and acute megakaryoblastic leukemia. Herein we review these studies including discussion of the functional significance of cohesin inactivation in tumorigenesis and potential therapeutic mechanisms to selectively target cancers harboring cohesin mutations. PMID:24856830

Solomon, David A; Kim, Jung-Sik; Waldman, Todd

2014-06-01

76

Cohesin gene mutations in tumorigenesis: from discovery to clinical significance  

PubMed Central

Cohesin is a multi-protein complex composed of four core subunits (SMC1A, SMC3, RAD21, and either STAG1 or STAG2) that is responsible for the cohesion of sister chromatids following DNA replication until its cleavage during mitosis thereby enabling faithful segregation of sister chromatids into two daughter cells. Recent cancer genomics analyses have discovered a high frequency of somatic mutations in the genes encoding the core cohesin subunits as well as cohesin regulatory factors (e.g. NIPBL, PDS5B, ESPL1) in a select subset of human tumors including glioblastoma, Ewing sarcoma, urothelial carcinoma, acute myeloid leukemia, and acute megakaryoblastic leukemia. Herein we review these studies including discussion of the functional significance of cohesin inactivation in tumorigenesis and potential therapeutic mechanisms to selectively target cancers harboring cohesin mutations. [BMB Reports 2014; 47(6): 299-310] PMID:24856830

Solomon, David A.; Kim, Jung-Sik; Waldman, Todd

2014-01-01

77

deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data  

PubMed Central

Gene fusions created by somatic genomic rearrangements are known to play an important role in the onset and development of some cancers, such as lymphomas and sarcomas. RNA-Seq (whole transcriptome shotgun sequencing) is proving to be a useful tool for the discovery of novel gene fusions in cancer transcriptomes. However, algorithmic methods for the discovery of gene fusions using RNA-Seq data remain underdeveloped. We have developed deFuse, a novel computational method for fusion discovery in tumor RNA-Seq data. Unlike existing methods that use only unique best-hit alignments and consider only fusion boundaries at the ends of known exons, deFuse considers all alignments and all possible locations for fusion boundaries. As a result, deFuse is able to identify fusion sequences with demonstrably better sensitivity than previous approaches. To increase the specificity of our approach, we curated a list of 60 true positive and 61 true negative fusion sequences (as confirmed by RT-PCR), and have trained an adaboost classifier on 11 novel features of the sequence data. The resulting classifier has an estimated value of 0.91 for the area under the ROC curve. We have used deFuse to discover gene fusions in 40 ovarian tumor samples, one ovarian cancer cell line, and three sarcoma samples. We report herein the first gene fusions discovered in ovarian cancer. We conclude that gene fusions are not infrequent events in ovarian cancer and that these events have the potential to substantially alter the expression patterns of the genes involved; gene fusions should therefore be considered in efforts to comprehensively characterize the mutational profiles of ovarian cancer transcriptomes. PMID:21625565

McPherson, Andrew; Hormozdiari, Fereydoun; Zayed, Abdalnasser; Giuliany, Ryan; Ha, Gavin; Sun, Mark G. F.; Griffith, Malachi; Heravi Moussavi, Alireza; Senz, Janine; Melnyk, Nataliya; Pacheco, Marina; Marra, Marco A.; Hirst, Martin; Nielsen, Torsten O.; Sahinalp, S. Cenk; Huntsman, David; Shah, Sohrab P.

2011-01-01

78

Structure-based ligand design to overcome CYP inhibition in drug discovery projects.  

PubMed

Cytochrome P450 (CYP) enzymes are key players in xenobiotic metabolism, and inhibition of CYPs can therefore result in unwanted drug-drug interactions. Within drug discovery, CYP inhibition can cause delays in the progression of candidate drugs, or even premature closure of projects. During the past decade, a massive effort in the pharmaceutical industry and academic research has produced a wealth of structural information in the CYP field. In this short review, we will describe how structure-based approaches can be used in the pharmaceutical industry to work away from CYP inhibition, with a focus on the opportunities and challenges. We will show two examples from our own work where structural information on CYP2C9 and CYP3A4 inhibitor complexes have been successfully exploited in ongoing drug discovery projects. PMID:24642031

Brändén, Gisela; Sjögren, Tove; Schnecke, Volker; Xue, Yafeng

2014-07-01

79

Bioinformatic Screening of Autoimmune Disease Genes and Protein Structure Prediction with FAMS for Drug Discovery  

PubMed Central

Autoimmune diseases are often intractable because their causes are unknown. Identifying which genes contribute to these diseases may allow us to understand the pathogenesis, but it is difficult to determine which genes contribute to disease. Recently, epigenetic information has been considered to activate/deactivate disease-related genes. Thus, it may also be useful to study epigenetic information that differs between healthy controls and patients with autoimmune disease. Among several types of epigenetic information, promoter methylation is believed to be one of the most important factors. Here, we propose that principal component analysis is useful to identify specific gene promoters that are differently methylated between the normal healthy controls and patients with autoimmune disease. Full Automatic Modeling System (FAMS) was used to predict the three-dimensional structures of selected proteins and successfully inferred relatively confident structures. Several possibilities of the application to the drug discovery based on obtained structures are discussed. PMID:23855671

Ishida, Shigeharu; Umeyama, Hideaki; Iwadate, Mitsuo; Y-h, Taguchi

2014-01-01

80

PAGED: a pathway and gene-set enrichment database to enable molecular phenotype discoveries  

PubMed Central

Background Over the past decade, pathway and gene-set enrichment analysis has evolved into the study of high-throughput functional genomics. Owing to poorly annotated and incomplete pathway data, researchers have begun to combine pathway and gene-set enrichment analysis as well as network module-based approaches to identify crucial relationships between different molecular mechanisms. Methods To meet the new challenge of molecular phenotype discovery, in this work, we have developed an integrated online database, the Pathway And Gene Enrichment Database (PAGED), to enable comprehensive searches for disease-specific pathways, gene signatures, microRNA targets, and network modules by integrating gene-set-based prior knowledge as molecular patterns from multiple levels: the genome, transcriptome, post-transcriptome, and proteome. Results The online database we developed, PAGED http://bio.informatics.iupui.edu/PAGED is by far the most comprehensive public compilation of gene sets. In its current release, PAGED contains a total of 25,242 gene sets, 61,413 genes, 20 organisms, and 1,275,560 records from five major categories. Beyond its size, the advantage of PAGED lies in the explorations of relationships between gene sets as gene-set association networks (GSANs). Using colorectal cancer expression data analysis as a case study, we demonstrate how to query this database resource to discover crucial pathways, gene signatures, and gene network modules specific to colorectal cancer functional genomics. Conclusions This integrated online database lays a foundation for developing tools beyond third-generation pathway analysis approaches on for discovering molecular phenotypes, especially for disease-associated pathway/gene-set enrichment analysis. PMID:23046413

2012-01-01

81

Ontological Discovery Environment: A system for integrating gene-phenotype associations  

PubMed Central

The wealth of genomic technologies has enabled biologists to rapidly ascribe phenotypic characters to biological substrates. Central to effective biological investigation is the operational definition of the process under investigation. We propose an elucidation of categories of biological characters, including disease relevant traits, based on natural endogenous processes and experimentally observed biological networks, pathways and systems rather than on externally manifested constructs and current semantics such as disease names and processes. The Ontological Discovery Environment (ODE) is an Internet accessible resource for the storage, sharing, retrieval and analysis of phenotype-centered genomic data sets across species and experimental model systems. Any type of data set representing gene-phenotype relationships, such quantitative trait loci (QTL) positional candidates, literature reviews, microarray experiments, ontological or even meta-data, may serve as inputs. To demonstrate a use case leveraging the homology capabilities of ODE and its ability to synthesize diverse data sets, we conducted an analysis of genomic studies related to alcoholism. The core of ODE’s gene-set similarity, distance and hierarchical analysis is the creation of a bipartite network of gene-phenotype relations, a unique discrete graph approach to analysis that enables set-set matching of non-referential data. Gene sets are annotated with several levels of metadata, including community ontologies, while gene set translations compare models across species. Computationally derived gene sets are integrated into hierarchical trees based on gene-derived phenotype interdependencies. Automated set identifications are augmented by statistical tools which enable users to interpret the confidence of modeled results. This approach allows data integration and hypothesis discovery across multiple experimental contexts, regardless of the face similarity and semantic annotation of the experimental systems or species domain. PMID:19733230

Baker, Erich J.; Jay, Jeremy J.; Philip, Vivek M.; Zhang, Yun; Li, Zuopan; Kirova, Roumyana; Langston, Michael A.; Chesler, Elissa J.

2009-01-01

82

Designing and Developing a NASA Research Projects Knowledge Base and Implementing Knowledge Management and Discovery Techniques  

NASA Astrophysics Data System (ADS)

The Research Project Knowledge Base (RPKB) is currently being designed and will be implemented in a manner that is fully compatible and interoperable with enterprise architecture tools developed to support NASA's Applied Sciences Program. Through user needs assessment, collaboration with Stennis Space Center, Goddard Space Flight Center, and NASA's DEVELOP Staff personnel insight to information needs for the RPKB were gathered from across NASA scientific communities of practice. To enable efficient, consistent, standard, structured, and managed data entry and research results compilation a prototype RPKB has been designed and fully integrated with the existing NASA Earth Science Systems Components database. The RPKB will compile research project and keyword information of relevance to the six major science focus areas, 12 national applications, and the Global Change Master Directory (GCMD). The RPKB will include information about projects awarded from NASA research solicitations, project investigator information, research publications, NASA data products employed, and model or decision support tools used or developed as well as new data product information. The RPKB will be developed in a multi-tier architecture that will include a SQL Server relational database backend, middleware, and front end client interfaces for data entry. The purpose of this project is to intelligently harvest the results of research sponsored by the NASA Applied Sciences Program and related research program results. We present various approaches for a wide spectrum of knowledge discovery of research results, publications, projects, etc. from the NASA Systems Components database and global information systems and show how this is implemented in SQL Server database. The application of knowledge discovery is useful for intelligent query answering and multiple-layered database construction. Using advanced EA tools such as the Earth Science Architecture Tool (ESAT), RPKB will enable NASA and partner agencies to efficiently identify the significant results for new experiment directions and principle investigators to formulate experiment directions for new proposals.

Dabiru, L.; O'Hara, C. G.; Shaw, D.; Katragadda, S.; Anderson, D.; Kim, S.; Shrestha, B.; Aanstoos, J.; Frisbie, T.; Policelli, F.; Keblawi, N.

2006-12-01

83

Genes, genomes and identity. Projections on matter.  

PubMed

This paper aims to show that references to genes and genomes are counterproductive in legal and political understandings of what it is to be human and a unique individual. To support this claim, I will give a brief overview of the many incompatible meanings the term 'identity' has gathered in reference to genes or genome in the contexts of biology and family ancestry, personal identity, species identity. One finds various and incompatible understandings of these expressions. While genetics is usually considered to deliver definitive knowledge about history and the future, genomics seems to work with more complicated relations between DNA, inheritance and phenotype. In genomics, 'identity' is no longer about identification and status markers but about individualization. Regulatory and legal documents project from traits to genomes, implying that individuality is at least represented, if not created, in a unique genome. Boundaries between humans and other animals, between different 'kinds' of humans, and between all individual humans are re-established via reference to the chemical matter of DNA. My analysis will show how this trend is a reactionary response to modern understandings of identities as social products and that it ignores new biomedical understandings of human bodies. PMID:15828152

Hauskeller, Christine

2004-12-01

84

High-throughput platform for the discovery of elicitors of silent bacterial gene clusters.  

PubMed

Over the past decade, bacterial genome sequences have revealed an immense reservoir of biosynthetic gene clusters, sets of contiguous genes that have the potential to produce drugs or drug-like molecules. However, the majority of these gene clusters appear to be inactive for unknown reasons prompting terms such as "cryptic" or "silent" to describe them. Because natural products have been a major source of therapeutic molecules, methods that rationally activate these silent clusters would have a profound impact on drug discovery. Herein, a new strategy is outlined for awakening silent gene clusters using small molecule elicitors. In this method, a genetic reporter construct affords a facile read-out for activation of the silent cluster of interest, while high-throughput screening of small molecule libraries provides potential inducers. This approach was applied to two cryptic gene clusters in the pathogenic model Burkholderia thailandensis. The results not only demonstrate a prominent activation of these two clusters, but also reveal that the majority of elicitors are themselves antibiotics, most in common clinical use. Antibiotics, which kill B. thailandensis at high concentrations, act as inducers of secondary metabolism at low concentrations. One of these antibiotics, trimethoprim, served as a global activator of secondary metabolism by inducing at least five biosynthetic pathways. Further application of this strategy promises to uncover the regulatory networks that activate silent gene clusters while at the same time providing access to the vast array of cryptic molecules found in bacteria. PMID:24808135

Seyedsayamdost, Mohammad R

2014-05-20

85

High-throughput platform for the discovery of elicitors of silent bacterial gene clusters  

PubMed Central

Over the past decade, bacterial genome sequences have revealed an immense reservoir of biosynthetic gene clusters, sets of contiguous genes that have the potential to produce drugs or drug-like molecules. However, the majority of these gene clusters appear to be inactive for unknown reasons prompting terms such as “cryptic” or “silent” to describe them. Because natural products have been a major source of therapeutic molecules, methods that rationally activate these silent clusters would have a profound impact on drug discovery. Herein, a new strategy is outlined for awakening silent gene clusters using small molecule elicitors. In this method, a genetic reporter construct affords a facile read-out for activation of the silent cluster of interest, while high-throughput screening of small molecule libraries provides potential inducers. This approach was applied to two cryptic gene clusters in the pathogenic model Burkholderia thailandensis. The results not only demonstrate a prominent activation of these two clusters, but also reveal that the majority of elicitors are themselves antibiotics, most in common clinical use. Antibiotics, which kill B. thailandensis at high concentrations, act as inducers of secondary metabolism at low concentrations. One of these antibiotics, trimethoprim, served as a global activator of secondary metabolism by inducing at least five biosynthetic pathways. Further application of this strategy promises to uncover the regulatory networks that activate silent gene clusters while at the same time providing access to the vast array of cryptic molecules found in bacteria. PMID:24808135

Seyedsayamdost, Mohammad R.

2014-01-01

86

Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis  

PubMed Central

Background The antifungal therapy caspofungin is a semi-synthetic derivative of pneumocandin B0, a lipohexapeptide produced by the fungus Glarea lozoyensis, and was the first member of the echinocandin class approved for human therapy. The nonribosomal peptide synthetase (NRPS)-polyketide synthases (PKS) gene cluster responsible for pneumocandin biosynthesis from G. lozoyensis has not been elucidated to date. In this study, we report the elucidation of the pneumocandin biosynthetic gene cluster by whole genome sequencing of the G. lozoyensis wild-type strain ATCC 20868. Results The pneumocandin biosynthetic gene cluster contains a NRPS (GLNRPS4) and a PKS (GLPKS4) arranged in tandem, two cytochrome P450 monooxygenases, seven other modifying enzymes, and genes for L-homotyrosine biosynthesis, a component of the peptide core. Thus, the pneumocandin biosynthetic gene cluster is significantly more autonomous and organized than that of the recently characterized echinocandin B gene cluster. Disruption mutants of GLNRPS4 and GLPKS4 no longer produced the pneumocandins (A0 and B0), and the ?glnrps4 and ?glpks4 mutants lost antifungal activity against the human pathogenic fungus Candida albicans. In addition to pneumocandins, the G. lozoyensis genome encodes a rich repertoire of natural product-encoding genes including 24 PKSs, six NRPSs, five PKS-NRPS hybrids, two dimethylallyl tryptophan synthases, and 14 terpene synthases. Conclusions Characterization of the gene cluster provides a blueprint for engineering new pneumocandin derivatives with improved pharmacological properties. Whole genome estimation of the secondary metabolite-encoding genes from G. lozoyensis provides yet another example of the huge potential for drug discovery from natural products from the fungal kingdom. PMID:23688303

2013-01-01

87

Discovery Medicine, Volume 4, Number 24, Pages 396-400, December 2004 single inherited mutant gene may be enough to  

E-print Network

396 Discovery Medicine, Volume 4, Number 24, Pages 396-400, December 2004 A single inherited mutant gene may be enough to cause a very high cancer risk. Single-mutation cases have provided much insight of a mutation to a single gene. Males with a brother or father who has suffered prostate cancer are more likely

Frank, Steven A.

88

Discovery of a novel tumour metastasis-promoting gene, NVM-1.  

PubMed

We have previously reported that over-expression of a panel of 119 genes correlates with the metastatic potential of pancreatic carcinoma cells. We sought to identify and functionally characterize candidate tumour metastasis promoting genes among this library using a secondary phenotype-assisted screen. Here we report the discovery of the metastasis-promoting function of a hitherto not characterized gene located on chromosome 14 (ORF138), which we have named 'novel metastasis-promoting gene 1' (NVM-1). The NVM-1 transcript is extensively alternatively spliced, is expressed endogenously in a number of different tissues, and is strongly over-expressed at the protein level in a variety of human tumour types. Importantly, NVM-1 expression stimulates the migratory and invasive behaviour of tumour cells and promotes metastasis formation in experimental animals in vivo. Up-regulation of FMNL2 and MT1E and down-regulation of TIMP4 and MHC-I is observed as a consequence of NVM-1 expression. Together these data identify NVM-1 as a gene that is functionally involved in tumour metastasis, and suggest that NVM-1 may constitute a promising therapeutic target for inhibition of tumour metastasis. PMID:21744341

Thiele, Wilko; Novac, Natalia; Mink, Sigrun; Schreiber, Caroline; Plaumann, Diana; Fritzmann, Johannes; Cremers, Natascha; Rothley, Melanie; Schwager, Christian; Regiert, Thomas; Huber, Peter E; Stein, Ulrike; Schlag, Peter; Moll, Jürgen; Abdollahi, Amir; Sleeman, Jonathan P

2011-09-01

89

MORPHIN: a web tool for human disease research by projecting model organism biology onto a human integrated gene network  

PubMed Central

Despite recent advances in human genetics, model organisms are indispensable for human disease research. Most human disease pathways are evolutionally conserved among other species, where they may phenocopy the human condition or be associated with seemingly unrelated phenotypes. Much of the known gene-to-phenotype association information is distributed across diverse databases, growing rapidly due to new experimental techniques. Accessible bioinformatics tools will therefore facilitate translation of discoveries from model organisms into human disease biology. Here, we present a web-based discovery tool for human disease studies, MORPHIN (model organisms projected on a human integrated gene network), which prioritizes the most relevant human diseases for a given set of model organism genes, potentially highlighting new model systems for human diseases and providing context to model organism studies. Conceptually, MORPHIN investigates human diseases by an orthology-based projection of a set of model organism genes onto a genome-scale human gene network. MORPHIN then prioritizes human diseases by relevance to the projected model organism genes using two distinct methods: a conventional overlap-based gene set enrichment analysis and a network-based measure of closeness between the query and disease gene sets capable of detecting associations undetectable by the conventional overlap-based methods. MORPHIN is freely accessible at http://www.inetbio.org/morphin. PMID:24861622

Hwang, Sohyun; Kim, Eiru; Yang, Sunmo; Marcotte, Edward M.; Lee, Insuk

2014-01-01

90

Controlling False Discoveries in Multidimensional Directional Decisions, with Applications to Gene Expression Data on Ordered Categories  

PubMed Central

Summary Microarray gene expression studies over ordered categories are routinely conducted to gain insights into biological functions of genes and the underlying biological processes. Some common experiments are time-course/dose-response experiments where a tissue or cell-line is exposed for different doses and/or durations of time to a chemical. A goal of such studies is to identify gene expression patterns/profiles over the ordered categories. This problem can be formulated as a multiple testing problem where for each gene the null hypothesis of no difference between the successive mean gene expressions are tested and further directional decisions are made if it is rejected. Much of the existing multiple testing procedures are devised for controlling the usual false discovery rate (FDR) rather than the mixed directional FDR, the expected proportion of Type I and directional errors among all rejections. Benjamini and Yekutieli (2005) proved that an augmentation of the usual Benjamini-Hochberg (BH) procedure can control the mixed directional FDR while testing simple null hypotheses against two-sided alternatives in terms of one dimensional parameters. In this article, we consider the problem of controlling the mixed directional FDR involving multidimensional parameters. To deal with this problem, we develop a procedure extending that of Benjamini and Yekutieli based on the Bonferroni test for each gene. A proof is given for its mixed directional FDR control when the underlying test statistics are independent across the genes. The results of a simulation study evaluating its performance under independence as well as under dependence of the underlying test statistics across the genes relative to other relevant procedures are reported. Finally, the proposed methodology is applied to a time-course microarray data obtained by Lobenhofer et al. (2002). We identified several important cell-cycle genes, such as DNA replication/repair gene MCM4 and replication factor subunit C2, which were not identified by the previous analyses of the same data by Lobenhofer et al. (2002) and Peddada et al. (2003). Although some of our findings overlap with previous findings, we identify several other genes that compliment the results of Lobenhofer et al. (2002). PMID:19645703

Guo, Wenge; Sarkar, Sanat K.; Peddada, Shyamal D.

2009-01-01

91

The Berkeley Drosophila Genome Project Gene Disruption Project: Single P-Element Insertions Mutating 25% of Vital Drosophila Genes  

Microsoft Academic Search

A fundamental goal of genetics and functional genomics is to identify and mutate every gene in model organisms such as Drosophila melanogaster. The Berkeley Drosophila Genome Project (BDGP) gene disruption project generates single P-element insertion strains that each mutate unique genomic open reading frames. Such strains strongly facilitate further genetic and molecular studies of the disrupted loci, but it has

Allan C. Spradling; Dianne Stern; Amy Beaton; E. Jay Rhem; Todd Laverty; Nicole Mozden; Sima Misra; Gerald M. Rubin

92

Gene-associated single nucleotide polymorphism discovery in perennial ryegrass (Lolium perenne L.).  

PubMed

Molecular genetic marker development in perennial ryegrass has largely been dependent on anonymous sequence variation. The availability of a large-scale EST resource permits the development of functionally-associated genetic markers based on SNP variation in candidate genes. Genic SNP loci and associated haplotypes are suitable for implementation in molecular breeding of outbreeding forage species. Strategies for in vitro SNP discovery through amplicon cloning and sequencing have been designed and implemented. Putative SNPs were identified within and between the parents of the F(1)(NA(6) x AU(6)) genetic mapping family and were validated among progeny individuals. Proof-of-concept for the process was obtained using the drought tolerance-associated LpASRa2 gene. SNP haplotype structures were determined and correlated with predicted amino acid changes. Gene-length LD was evaluated across diverse germplasm collections. A survey of SNP variation across 100 candidate genes revealed a high frequency of SNP incidence (c. 1 per 54 bp), with similar proportions in exons and introns. A proportion (c. 50%) of the validated genic SNPs were assigned to the F(1)(NA(6) x AU(6)) genetic map, showing high levels of coincidence with previously mapped RFLP loci. The perennial ryegrass SNP resource will enable genetic map integration, detailed LD studies and selection of superior allele content during varietal development. PMID:16708235

Cogan, Noel O I; Ponting, Rebecca C; Vecchies, Anita C; Drayton, Michelle C; George, Julie; Dracatos, Peter M; Dobrowolski, Mark P; Sawbridge, Timothy I; Smith, Kevin F; Spangenberg, Germán C; Forster, John W

2006-08-01

93

Using Osteoclast Differentiation as a Model for Gene Discovery in an Undergraduate Cell Biology Laboratory  

ERIC Educational Resources Information Center

A key goal of molecular/cell biology/biotechnology is to identify essential genes in virtually every physiological process to uncover basic mechanisms of cell function and to establish potential targets of drug therapy combating human disease. This article describes a semester-long, project-oriented molecular/cellular/biotechnology laboratory…

Birnbaum, Mark J.; Picco, Jenna; Clements, Meghan; Witwicka, Hanna; Yang, Meiheng; Hoey, Margaret T.; Odgren, Paul R.

2010-01-01

94

Resequencing and Comparative Genomics of Stagonospora nodorum: Sectional Gene Absence and Effector Discovery  

PubMed Central

Stagonospora nodorum is an important wheat (Triticum aestivum) pathogen in many parts of the world, causing major yield losses. It was the first species in the large fungal Dothideomycete class to be genome sequenced. The reference genome sequence (SN15) has been instrumental in the discovery of genes encoding necrotrophic effectors that induce disease symptoms in specific host genotypes. Here we present the genome sequence of two further S. nodorum strains (Sn4 and Sn79) that differ in their effector repertoire from the reference. Sn79 is avirulent on wheat and produces no apparent effectors when infiltrated onto many cultivars and mapping population parents. Sn4 is pathogenic on wheat and has virulences not found in SN15. The new strains, sequenced with short-read Illumina chemistry, are compared with SN15 by a combination of mapping and de novo assembly approaches. Each of the genomes contains a large number of strain-specific genes, many of which have no meaningful similarity to any known gene. Large contiguous sections of the reference genome are absent in the two newly sequenced strains. We refer to these differences as “sectional gene absences.” The presence of genes in pathogenic strains and absence in Sn79 is added to computationally predicted properties of known proteins to produce a list of likely effector candidates. Transposon insertion was observed in the mitochondrial genomes of virulent strains where the avirulent strain retained the likely ancestral sequence. The study suggests that short-read enabled comparative genomics is an effective way to both identify new S. nodorum effector candidates and to illuminate evolutionary processes in this species. PMID:23589517

Syme, Robert Andrew; Hane, James K.; Friesen, Timothy L.; Oliver, Richard P.

2013-01-01

95

IMPEE PhD Opportunity Project title: Cyber-physical Systems (CPS) for knowledge discovery, data exploration and human factors  

E-print Network

IMPEE PhD Opportunity Project title: Cyber-physical Systems (CPS) for knowledge discovery, data exploration and human factors research Supervisor(s): T. Lim, J.M. Ritchie Abstract CPS is an engineering/augmented/mixed reality spaces. R&D interests include (but not limited to): Aural or narrative guidance for product design

Greenaway, Alan

96

A genome-wide cis-regulatory element discovery method based on promoter sequences and gene co-expression networks  

PubMed Central

Background Deciphering cis-regulatory networks has become an attractive yet challenging task. This paper presents a simple method for cis-regulatory network discovery which aims to avoid some of the common problems of previous approaches. Results Using promoter sequences and gene expression profiles as input, rather than clustering the genes by the expression data, our method utilizes co-expression neighborhood information for each individual gene, thereby overcoming the disadvantages of current clustering based models which may miss specific information for individual genes. In addition, rather than using a motif database as an input, it implements a simple motif count table for each enumerated k-mer for each gene promoter sequence. Thus, it can be used for species where previous knowledge of cis-regulatory motifs is unknown and has the potential to discover new transcription factor binding sites. Applications on Saccharomyces cerevisiae and Arabidopsis have shown that our method has a good prediction accuracy and outperforms a phylogenetic footprinting approach. Furthermore, the top ranked gene-motif regulatory clusters are evidently functionally co-regulated, and the regulatory relationships between the motifs and the enriched biological functions can often be confirmed by literature. Conclusions Since this method is simple and gene-specific, it can be readily utilized for insufficiently studied species or flexibly used as an additional step or data source for previous transcription regulatory networks discovery models. PMID:23368633

2013-01-01

97

Functional Linkage between Genes That Regulate Osmotic Stress Responses and Multidrug Resistance Transporters: Challenges and Opportunities for Antibiotic Discovery  

PubMed Central

All cells need to protect themselves against the osmotic challenges of their environment by maintaining low permeability to ions across their cell membranes. This is a basic principle of cellular function, which is reflected in the interactions among ion transport and drug efflux genes that have arisen during cellular evolution. Thus, upon exposure to pore-forming antibiotics such as amphotericin B (AmB) or daptomycin (Dap), sensitive cells overexpress common resistance genes to protect themselves from added osmotic challenges. These genes share pathway interactions with the various types of multidrug resistance (MDR) transporter genes, which both preserve the native lipid membrane composition and at the same time eliminate disruptive hydrophobic molecules that partition excessively within the lipid bilayer. An increased understanding of the relationships between the genes (and their products) that regulate osmotic stress responses and MDR transporters will help to identify novel strategies and targets to overcome the current stalemate in drug discovery. PMID:24295980

2014-01-01

98

Functional linkage between genes that regulate osmotic stress responses and multidrug resistance transporters: challenges and opportunities for antibiotic discovery.  

PubMed

All cells need to protect themselves against the osmotic challenges of their environment by maintaining low permeability to ions across their cell membranes. This is a basic principle of cellular function, which is reflected in the interactions among ion transport and drug efflux genes that have arisen during cellular evolution. Thus, upon exposure to pore-forming antibiotics such as amphotericin B (AmB) or daptomycin (Dap), sensitive cells overexpress common resistance genes to protect themselves from added osmotic challenges. These genes share pathway interactions with the various types of multidrug resistance (MDR) transporter genes, which both preserve the native lipid membrane composition and at the same time eliminate disruptive hydrophobic molecules that partition excessively within the lipid bilayer. An increased understanding of the relationships between the genes (and their products) that regulate osmotic stress responses and MDR transporters will help to identify novel strategies and targets to overcome the current stalemate in drug discovery. PMID:24295980

Cohen, B Eleazar

2014-01-01

99

Gene-based single nucleotide polymorphism discovery in bovine muscle using next-generation transcriptomic sequencing  

PubMed Central

Background Genetic information based on molecular markers has increasingly being used in cattle breeding improvement programmes, as a mean to improve conventionally phenotypic selection. Advances in molecular genetics have led to the identification of several genetic markers associated with genes affecting economic traits. Until recently, the identification of the causative genetic variants involved in the phenotypes of interest has remained a difficult task. The advent of novel sequencing technologies now offers a new opportunity for the identification of such variants. Despite sequencing costs plummeting, sequencing whole-genomes or large targeted regions is still too expensive for most laboratories. A transcriptomic-based sequencing approach offers a cheaper alternative to identify a large number of polymorphisms and possibly to discover causative variants. In the present study, we performed a gene-based single nucleotide polymorphism (SNP) discovery analysis in bovine Longissimus thoraci, using RNA-Seq. To our knowledge, this represents the first study done in bovine muscle. Results Messenger RNAs from Longissimus thoraci from three Limousin bull calves were subjected to high-throughput sequencing. Approximately 36–46 million paired-end reads were obtained per library. A total of 19,752 transcripts were identified and 34,376 different SNPs were detected. Fifty-five percent of the SNPs were found in coding regions and ~22% resulted in an amino acid change. Applying a very stringent SNP quality threshold, we detected 8,407 different high-confidence SNPs, 18% of which are non synonymous coding SNPs. To analyse the accuracy of RNA-Seq technology for SNP detection, 48 SNPs were selected for validation by genotyping. No discrepancies were observed when using the highest SNP probability threshold. To test the usefulness of the identified SNPs, the 48 selected SNPs were assessed by genotyping 93 bovine samples, representing mostly the nine major breeds used in France. Principal component analysis indicates a clear separation between the nine populations. Conclusions The RNA-Seq data and the collection of newly discovered coding SNPs improve the genomic resources available for cattle, especially for beef breeds. The large amount of variation present in genes expressed in Limousin Longissimus thoracis, especially the large number of non synonymous coding SNPs, may prove useful to study the mechanisms underlying the genetic variability of meat quality traits. PMID:23651547

2013-01-01

100

CancerGenes: a gene selection resource for cancer genome projects  

Microsoft Academic Search

The genome sequence framework provided by the human genome project allows us to precisely map human genetic variations in order to study their association with disease and their direct effects on gene function. Since the description of tumor suppressor genes and oncogenes several decades ago, both germ-line variations and somatic mutations have been established to be important in cancer—in terms

Maureen E. Higgins; Martine Claremont; John E. Major; Chris Sander; Alex E. Lash

2007-01-01

101

elemental discoveries  

NSDL National Science Digital Library

Experienced science journalist David Bradley serves up this resource on current chemical happenings. Tracking some of the discoveries and controversies at the forefront of chemistry, each issue of elemental discoveries summarizes a range of newsworthy topics, from gene control and tubular sensors to singing fish. In addition to the current issue, readers may browse past issues beginning December 1997. Two additional sections, Elemental Reviews and Book Sale, provide brief commentary on or descriptions (with UK prices) of related resources.

102

Genome-Scale Discovery of Cell Wall Biosynthesis Genes in Populus (JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)  

ScienceCinema

Wellington Muchero from Oak Ridge National Laboratory gives a talk titled "Discovery of Cell Wall Biosynthesis Genes in Populus" at the JGI 7th Annual Users Meeting: Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, California.

Muchero, Wellington [Oak Ridge National Laboratory

2013-01-22

103

Bioinformatics Approaches to Biomarker Discovery BIOC 218/ BMI 231  

E-print Network

1 Bioinformatics Approaches to Biomarker Discovery BIOC 218/ BMI 231 FINAL PROJECT March 2007 Seema the biologically relevant information. It is important that microarray technology and bioinformatics approaches and therapeutic target discovery. Adapted from Narayanan, R. (2007). "Bioinformatics approaches to cancer gene

104

drug discovery drug discovery  

E-print Network

drug discovery at Purdue #12;drug discovery 2 #12;drug discovery 3 Introduction The drug discovery and innovative drug candidates to treat chronic and acute illnesses. Our researchers also continue to be invested in various approaches to drug discovery, which include understanding of drug targets for future drug

105

Discrimination discovery in scientific project evaluation: A case study$ Andrea Romei, Salvatore Ruggieri and Franco Turini  

E-print Network

records is a non-trivial problem. It requires the design of ad-hoc methods and techniques of analysis, experimentation with real data. This paper contributes by presenting a case study on gender discrimination discovery process. Gender bias in scientific research is a challenging problem, that has been tackled

Ruggieri, Salvatore

106

The BDGP gene disruption project: Single transposon insertions associated with 40 percent of Drosophila genes  

SciTech Connect

The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in more than 30,000 fly strains were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6,300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7,140 lines. It now includes individual lines predicted to disrupt 5,362 of the 13,666 currently annotated Drosophila genes (39 percent). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene mis-expression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool.

Bellen, Hugo J.; Levis, Robert W.; Liao, Guochun; He, Yuchun; Carlson, Joseph W.; Tsang, Garson; Evans-Holm, Martha; Hiesinger, P. Robin; Schulze, Karen L.; Rubin, Gerald M.; Hoskins, Roger A.; Spradling, Allan C.

2004-01-13

107

The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes.  

PubMed Central

The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in >30,000 fly strains were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7140 lines. It now includes individual lines predicted to disrupt 5362 of the 13,666 currently annotated Drosophila genes (39%). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene misexpression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool. PMID:15238527

Bellen, Hugo J; Levis, Robert W; Liao, Guochun; He, Yuchun; Carlson, Joseph W; Tsang, Garson; Evans-Holm, Martha; Hiesinger, P Robin; Schulze, Karen L; Rubin, Gerald M; Hoskins, Roger A; Spradling, Allan C

2004-01-01

108

A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules  

Microsoft Academic Search

To elucidate gene function on a global scale, we identified pairs of genes that are coexpressed over 3182 DNA microarrays from humans, flies, worms, and yeast. We found 22,163 such coexpression relationships, each of which has been conserved across evolution. This conservation implies that the coexpression of these gene pairs confers a selective advantage and therefore that these genes are

Joshua M. Stuart; Eran Segal; Daphne Koller; Stuart K. Kim

2003-01-01

109

Ataxin1L is a regulator of HSC function highlighting the utility of cross-tissue comparisons for gene discovery.  

PubMed

Hematopoietic stem cells (HSCs) are rare quiescent cells that continuously replenish the cellular components of the peripheral blood. Observing that the ataxia-associated gene Ataxin-1-like (Atxn1L) was highly expressed in HSCs, we examined its role in HSC function through in vitro and in vivo assays. Mice lacking Atxn1L had greater numbers of HSCs that regenerated the blood more quickly than their wild-type counterparts. Molecular analyses indicated Atxn1L null HSCs had gene expression changes that regulate a program consistent with their higher level of proliferation, suggesting that Atxn1L is a novel regulator of HSC quiescence. To determine if additional brain-associated genes were candidates for hematologic regulation, we examined genes encoding proteins from autism- and ataxia-associated protein-protein interaction networks for their representation in hematopoietic cell populations. The interactomes were found to be highly enriched for proteins encoded by genes specifically expressed in HSCs relative to their differentiated progeny. Our data suggest a heretofore unappreciated similarity between regulatory modules in the brain and HSCs, offering a new strategy for novel gene discovery in both systems. PMID:23555280

Kahle, Juliette J; Souroullas, George P; Yu, Peng; Zohren, Fabian; Lee, Yoontae; Shaw, Chad A; Zoghbi, Huda Y; Goodell, Margaret A

2013-03-01

110

Discovery of Possible Gene Relationships through the Application of Self-Organizing Maps to DNA Microarray Databases  

PubMed Central

DNA microarrays and cell cycle synchronization experiments have made possible the study of the mechanisms of cell cycle regulation of Saccharomyces cerevisiae by simultaneously monitoring the expression levels of thousands of genes at specific time points. On the other hand, pattern recognition techniques can contribute to the analysis of such massive measurements, providing a model of gene expression level evolution through the cell cycle process. In this paper, we propose the use of one of such techniques –an unsupervised artificial neural network called a Self-Organizing Map (SOM)–which has been successfully applied to processes involving very noisy signals, classifying and organizing them, and assisting in the discovery of behavior patterns without requiring prior knowledge about the process under analysis. As a test bed for the use of SOMs in finding possible relationships among genes and their possible contribution in some biological processes, we selected 282 S. cerevisiae genes that have been shown through biological experiments to have an activity during the cell cycle. The expression level of these genes was analyzed in five of the most cited time series DNA microarray databases used in the study of the cell cycle of this organism. With the use of SOM, it was possible to find clusters of genes with similar behavior in the five databases along two cell cycles. This result suggested that some of these genes might be biologically related or might have a regulatory relationship, as was corroborated by comparing some of the clusters obtained with SOMs against a previously reported regulatory network that was generated using biological knowledge, such as protein-protein interactions, gene expression levels, metabolism dynamics, promoter binding, and modification, regulation and transport of proteins. The methodology described in this paper could be applied to the study of gene relationships of other biological processes in different organisms. PMID:24699245

Chavez-Alvarez, Rocio; Chavoya, Arturo; Mendez-Vazquez, Andres

2014-01-01

111

Knowledge Discovery Nuggets Directory  

NSDL National Science Digital Library

Knowledge Discovery Nuggets is both a web site and an associated newsletter. The newsletter focuses on the latest research, new applications, conference announcements, and news about data mining and knowledge discovery. The web site offers a large index of categorized pointers to data mining and knowledge discovery software, informative reference materials, related research projects, data sets, and much more. While somewhat difficult to navigate, Knowledge Discovery Nuggets offers an excellent place to start a data mining or knowledge discovery related search.

112

Single nucleotide polymorphism (SNP) discovery in mammals: a targeted-gene approach  

Microsoft Academic Search

Single nucleotide polymorphisms (SNPs) have rarely been exploited in nonhuman and nonmodel organism genetic studies. This is due partly to difficulties in finding SNPs in species where little DNA sequence data exist, as well as to a lack of robust and inexpensive genotyping methods. We have explored one SNP discovery method for molecular ecology, evolution, and conservation studies to evaluate

NICOLA AITKEN; STEVEN SMITH; CARSTEN SCHWARZ; PHILLIP A. M ORIN

2004-01-01

113

Discovery of Candidate Genes for Stallion Fertility from the Horse Y Chromosome  

E-print Network

The genetic component of mammalian male fertility is complex and involves thousands of genes. The majority of these genes are distributed on autosomes and the X chromosome, while a small number are located on the Y chromosome. Human and mouse...

Paria, Nandina

2012-02-14

114

H-InvDB in 2013: an omics study platform for human functional gene and transcript discovery  

PubMed Central

H-InvDB (http://www.h-invitational.jp/) is a comprehensive human gene database started in 2004. In the latest version, H-InvDB 8.0, a total of 244 709 human complementary DNA was mapped onto the hg19 reference genome and 43 829 gene loci, including nonprotein-coding ones, were identified. Of these loci, 35 631 were identified as potential protein-coding genes, and 22 898 of these were identical to known genes. In our analysis, 19 309 annotated genes were specific to H-InvDB and not found in RefSeq and Ensembl. In fact, 233 genes of the 19 309 turned out to have protein functions in this version of H-InvDB; they were annotated as unknown protein functions in the previous version. Furthermore, 11 genes were identified as known Mendelian disorder genes. It is advantageous that many biologically functional genes are hidden in the H-InvDB unique genes. As large-scale proteomic projects have been conducted to elucidate the functions of all human proteins, we have enhanced the proteomic information with an advanced protein view and new subdatabase of protein complexes (Protein Complex Database with quality index). We propose that H-InvDB is an important resource for finding novel candidate targets for medical care and drug development. PMID:23197657

Takeda, Jun-ichi; Yamasaki, Chisato; Murakami, Katsuhiko; Nagai, Yoko; Sera, Miho; Hara, Yuichiro; Obi, Nobuo; Habara, Takuya; Gojobori, Takashi; Imanishi, Tadashi

2013-01-01

115

Available online at www.sciencedirect.com From mutations to MAGIC: resources for gene discovery,  

E-print Network

aspect of modern plant biology. The identification of genes underlying simply inherited traits has been The dissection of gene-trait associations and its translation into practice through plant breeding is a central very successful. However, the identification of gene-trait associations for complex (multi

Kihara, Daisuke

116

Assessment of discretization techniques for relevant pattern discovery from gene expression data  

E-print Network

boolean matrices that encode gene properties. To take the most from these approaches, a needed step concerns gene prop- erty encoding (e.g., over-expression) and its need for the discretization of raw gene, computed from raw expression data and from the vari- ous derived boolean matrices. Thanks to a new

Boulicaut, Jean-François

117

Discovery of sequence motifs related to coexpression of genes using evolutionary computation  

Microsoft Academic Search

Transcription factors are key regulatory elements that control gene expression. Recognition of transcription factor binding site (TFBS) motifs in the upstream region of coexpressed genes is therefore critical towards a true understanding of the regulations of gene expression. The task of discovering eukaryotic TFBSs remains a challenging problem. Here, we demonstrate that evolutionary computation can be used to search for

Gary B. Fogel; Dana G. Weekes; Gabor Varga; Ernst R. Dow; Harry B. Harlow; Jude E. Onyia; Chen Su

2004-01-01

118

Rapid and accurate large-scale genotyping of duplicated genes and discovery of novel sites of interlocus gene conversion  

PubMed Central

Over 900 genes have been annotated within duplicated regions of the human genome, yet their functions and potential roles in disease remain largely unknown. One major obstacle has been our inability to accurately and comprehensively assay genetic variation for these genes in a high-throughput manner. We developed a sequencing-based method for rapid and high-throughput genotyping of duplicated genes using molecular inversion probes designed to unique paralogous sequence variants. We apply this method to genotype all members of two gene families, SRGAP2 and RH, among a diversity panel of 1,056 humans. The approach can accurately distinguish copy number in paralogs having up to ?99.6% sequence identity, identify small gene-disruptive deletions, detect single nucleotide variants, define breakpoints of unequal crossover, and discover regions of interlocus gene conversion. Our analysis of SRGAP2 suggests that nonreciprocal genetic exchange akin to interlocus gene conversion can occur over long distances (> 80 Mbp) between paralogs. The ability to rapidly and accurately genotype multiple gene families in thousands of individuals at low cost enables the development of genome-wide gene conversion maps and unlocks many duplicated genes for association with human traits. PMID:23892896

Nuttle, Xander; Huddleston, John; O'Roak, Brian J.; Antonacci, Francesca; Fichera, Marco; Romano, Corrado; Shendure, Jay; Eichler, Evan E.

2013-01-01

119

Discovery of a novel gene involved in autolysis of Clostridium cells.  

PubMed

Cell autolysis plays important physiological roles in the life cycle of clostridial cells. Understanding the genetic basis of the autolysis phenomenon of pathogenic Clostridium or solvent producing Clostridium cells might provide new insights into this important species. Genes that might be involved in autolysis of Clostridium acetobutylicum, a model clostridial species, were investigated in this study. Twelve putative autolysin genes were predicted in C. acetobutylicum DSM 1731 genome through bioinformatics analysis. Of these 12 genes, gene SMB_G3117 was selected for testing the in tracellular autolysin activity, growth profile, viable cell numbers, and cellular morphology. We found that overexpression of SMB_G3117 gene led to earlier ceased growth, significantly increased number of dead cells, and clear electrolucent cavities, while disruption of SMB_G3117 gene exhibited remarkably reduced intracellular autolysin activity. These results indicate that SMB_G3117 is a novel gene involved in cellular autolysis of C. acetobutylicum. PMID:23702687

Yang, Liejian; Bao, Guanhui; Zhu, Yan; Dong, Hongjun; Zhang, Yanping; Li, Yin

2013-06-01

120

Culture in global business transformation projects : the discovery of a grounded theory.  

E-print Network

??Presently organisations engage in what is termed as Global Business Transformation Projects [GBTPs], for consolidating, innovating, transforming and restructuring their processes and business strategies while… (more)

Reiter, Sebastian

2012-01-01

121

Discovery of nucleotide polymorphisms in the Musa gene pool by Ecotilling  

Microsoft Academic Search

Musa (banana and plantain) is an important genus for the global export market and in local markets where it provides staple food\\u000a for approximately 400 million people. Hybridization and polyploidization of several (sub)species, combined with vegetative\\u000a propagation and human selection have produced a complex genetic history. We describe the application of the Ecotilling method\\u000a for the discovery and characterization of nucleotide

Bradley J. Till; Joanna Jankowicz-Cieslak; László Sági; Owen A. Huynh; Hiroe Utsushi; Rony Swennen; Ryohei Terauchi

2010-01-01

122

Discovery of sequence motifs related to coexpression of genes using evolutionary computation  

PubMed Central

Transcription factors are key regulatory elements that control gene expression. Recognition of transcription factor binding site (TFBS) motifs in the upstream region of coexpressed genes is therefore critical towards a true understanding of the regulations of gene expression. The task of discovering eukaryotic TFBSs remains a challenging problem. Here, we demonstrate that evolutionary computation can be used to search for TFBSs in upstream regions of genes known to be coexpressed. Evolutionary computation was used to search for TFBSs of genes regulated by octamer-binding factor and nuclear factor kappa B. The discovered binding sites included experimentally determined known binding motifs as well as lists of putative, previously unknown TFBSs. We believe that this method to search nucleotide sequence information efficiently for similar motifs will be useful for discovering TFBSs that affect gene regulation. PMID:15266008

Fogel, Gary B.; Weekes, Dana G.; Varga, Gabor; Dow, Ernst R.; Harlow, Harry B.; Onyia, Jude E.; Su, Chen

2004-01-01

123

Long Serial Analysis of Gene Expression for Gene Discovery and Transcriptome Profiling in the Widespread Marine Coccolithophore Emiliania huxleyi  

Microsoft Academic Search

The abundant and widespread coccolithophore Emiliania huxleyi plays an important role in mediating CO2 exchange between the ocean and the atmosphere through its impact on marine photosynthesis and calcifica- tion. Here, we use long serial analysis of gene expression (SAGE) to identify E. huxleyi genes responsive to nitrogen (N) or phosphorus (P) starvation. Long SAGE is an elegant approach for

Sonya T. Dyhrman; Sheean T. Haley; Shanda R. Birkeland; Louie L. Wurch; Michael J. Cipriano; Andrew G. McArthur

2006-01-01

124

Comparative Toxicogenomics Database: a knowledgebase and discovery tool for chemical-gene-disease networks  

Microsoft Academic Search

The Comparative Toxicogenomics Database (CTD) is a curated database that promotes understanding about the effects of environmental chemicals on human health. Biocurators at CTD manually curate chemical-gene interactions, chemical-disease rela- tionships and gene-disease relationships from the literature. This strategy allows data to be integrated to construct chemical-gene-disease networks. CTD is unique in numerous respects: curation focuses on environmental chemicals; interactions

Allan Peter Davis; Cynthia G. Murphy; Cynthia A. Saraceni-richards; Michael C. Rosenstein; Thomas C. Wiegers; Carolyn J. Mattingly

2009-01-01

125

Markus Maeurer on the LifeGene project.  

PubMed

This year will see the full-scale roll-out of the LifeGene study. Coordinated by the Karolinska Institutet (Stockholm, Sweden), the project looks set to be one of the largest health studies performed in the world, aiming to enroll 500,000 Swedes in order to determine the relationship between disease and environmental, lifestyle and hereditary factors. International experts from a broad spectrum of scientific fields will collaborate on this project, including Mark Maeurer, Chair of the infections working group in LifeGene (www.lifegene.se). Maeurer leads the additional study on influenza-like illnesses, which is currently being run within the LifeGene project. Maeurer studied medicine in Germany, Switzerland and the USA. He is board-certified in medical microbiology, has served as Assistant Professor of Surgery at the University of Pittsburgh Medical School (PA, USA) in the Department of Surgical Oncology and Immunotherapy, as Professor of Medical Microbiology at the University of Mainz, Germany, and is now Professor of Clinical Immunology at the Microbiology and Tumor Cell Biology Center at the Karolinska Institutet. Maeurer has conducted experiments with nonhuman primate models to study TB vaccine take, with the aim to profile markers of immune protection. His general interests are in the field of immune reconstitution and memory immune responses, with a particular focus on gauging protective T-cell responses and antibody immune signatures using high-content peptide microarrays. He has published more than 100 original articles, ten book chapters and serves as a reviewer for a number of international scientific journals. PMID:20828278

Maeurer, Markus

2010-09-01

126

Albert Einstein researchers' gene discovery could improve treatment for acute myeloid leukemia  

Cancer.gov

Scientists at Albert Einstein College of Medicine of Yeshiva University have discovered, in a mouse model of acute myeloid leukemia, that the gene HLX is expressed at abnormally high levels in leukemia stem cells. Gene expression is the process by which a gene synthesizes the molecule that it codes for; an "over-expressed" gene makes its product in abnormally high amounts. These findings suggest that targeting elevated HLX expression may be a promising novel strategy for treating AML. The Albert Einstein College of Medicine is home to the Albert Einstein Cancer Center.

127

Molecular Profiling of Breast Cancer Cell Lines Defines Relevant Tumor Models and Provides a Resource for Cancer Gene Discovery  

PubMed Central

Background Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes–luminal A, luminal B, ERBB2-associated, basal-like and normal-like–with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs). Here, we studied a collection of breast cancer cell lines to catalog molecular profiles and to assess their relation to breast cancer subtypes. Methods Whole-genome DNA microarrays were used to profile gene expression and CNAs in a collection of 52 widely-used breast cancer cell lines, and comparisons were made to existing profiles of primary breast tumors. Hierarchical clustering was used to identify gene-expression subtypes, and Gene Set Enrichment Analysis (GSEA) to discover biological features of those subtypes. Genomic and transcriptional profiles were integrated to discover within high-amplitude CNAs candidate cancer genes with coordinately altered gene copy number and expression. Findings Transcriptional profiling of breast cancer cell lines identified one luminal and two basal-like (A and B) subtypes. Luminal lines displayed an estrogen receptor (ER) signature and resembled luminal-A/B tumors, basal-A lines were associated with ETS-pathway and BRCA1 signatures and resembled basal-like tumors, and basal-B lines displayed mesenchymal and stem/progenitor-cell characteristics. Compared to tumors, cell lines exhibited similar patterns of CNA, but an overall higher complexity of CNA (genetically simple luminal-A tumors were not represented), and only partial conservation of subtype-specific CNAs. We identified 80 high-level DNA amplifications and 13 multi-copy deletions, and the resident genes with concomitantly altered gene-expression, highlighting known and novel candidate breast cancer genes. Conclusions Overall, breast cancer cell lines were genetically more complex than tumors, but retained expression patterns with relevance to the luminal-basal subtype distinction. The compendium of molecular profiles defines cell lines suitable for investigations of subtype-specific pathobiology, cancer stem cell biology, biomarkers and therapies, and provides a resource for discovery of new breast cancer genes. PMID:19582160

Bocanegra, Melanie; Choi, Yoon-La; Girard, Luc; Gandhi, Jeet; Kwei, Kevin A.; Hernandez-Boussard, Tina; Wang, Pei; Gazdar, Adi F.; Minna, John D.; Pollack, Jonathan R.

2009-01-01

128

Analyzing Interaction of ?-, ?- and ?-opioid Receptor Gene Variants on Alcohol or Drug Dependence Using a Pattern Discovery-based Method  

PubMed Central

Background Polymorphisms in the ?-, ?- and ?-opioid receptor genes (OPRM1, OPRD1 and OPRK1) have been reported to be associated with substance (alcohol or drug) dependence. The influence of an individual gene on a disease trait should be more evident when analyzed in the context of gene-gene interactions. Thus, we assessed the joint effect of variants in these three opioid receptor genes on alcohol, cocaine, or opioid dependence. Methods Genotype data for 13 OPRM1 Single Nucleotide Polymorphisms (SNPs), 11 OPRD1 SNPs and seven OPRK1 SNPs were obtained from 382 European Americans (EAs) affected with substance dependence [among them, 318 with Alcohol Dependence (AD), 171 with Cocaine Dependence (CD), and 91 with Opioid Dependence (OD)] and 338 EA control subjects. We assessed the joint effect of OPRM1, OPRD1 and OPRK1 variants on AD, CD, or OD using a pattern discovery-based association test. Specific marker patterns (consisting of alleles of OPRM1, OPRD1 and OPRK1) that were significantly more frequent in AD, CD, or OD cases than in controls were identified. Results 12 significant patterns in the AD dataset, four significant patterns in the CD dataset, and 18 significant patterns in the OD dataset were identified. Moreover, the significance of most marker patterns was due primarily to OPRM1 variants and, to a lesser degree, OPRD1 variants. Conclusion Our findings suggest that variation in the above three opioid receptor genes can jointly influence the vulnerability of individuals to alcohol or drug dependence. Evidence provided by this study also supports previous biological findings that the interaction of the three opioid receptors can modulate the action of opioid and non-opioid drugs and alcohol. PMID:24533225

Li, Zhong; Zhang, Huiping

2013-01-01

129

Shotgun proteomics aids discovery of novel protein-coding genes, alternative splicing, and "resurrected" pseudogenes in the mouse genome.  

PubMed

Recent advances in proteomic mass spectrometry (MS) offer the chance to marry high-throughput peptide sequencing to transcript models, allowing the validation, refinement, and identification of new protein-coding loci. We present a novel pipeline that integrates highly sensitive and statistically robust peptide spectrum matching with genome-wide protein-coding predictions to perform large-scale gene validation and discovery in the mouse genome for the first time. In searching an excess of 10 million spectra, we have been able to validate 32%, 17%, and 7% of all protein-coding genes, exons, and splice boundaries, respectively. Moreover, we present strong evidence for the identification of multiple alternatively spliced translations from 53 genes and have uncovered 10 entirely novel protein-coding genes, which are not covered in any mouse annotation data sources. One such novel protein-coding gene is a fusion protein that spans the Ins2 and Igf2 loci to produce a transcript encoding the insulin II and the insulin-like growth factor 2-derived peptides. We also report nine processed pseudogenes that have unique peptide hits, demonstrating, for the first time, that they are not just transcribed but are translated and are therefore resurrected into new coding loci. This work not only highlights an important utility for MS data in genome annotation but also provides unique insights into the gene structure and propagation in the mouse genome. All these data have been subsequently used to improve the publicly available mouse annotation available in both the Vega and Ensembl genome browsers (http://vega.sanger.ac.uk). PMID:21460061

Brosch, Markus; Saunders, Gary I; Frankish, Adam; Collins, Mark O; Yu, Lu; Wright, James; Verstraten, Ruth; Adams, David J; Harrow, Jennifer; Choudhary, Jyoti S; Hubbard, Tim

2011-05-01

130

Mapping our genes: The genome projects: How big, how fast  

SciTech Connect

For the past 2 years, scientific and technical journals in biology and medicine have extensively covered a debate about whether and how to determine the function and order of human genes on human chromosomes and when to determine the sequence of molecular building blocks that comprise DNA in those chromosomes. In 1987, these issues rose to become part of the public agenda. The debate involves science, technology, and politics. Congress is responsible for /open quotes/writing the rules/close quotes/ of what various federal agencies do and for funding their work. This report surveys the points made so far in the debate, focusing on those that most directly influence the policy options facing the US Congress. Congressional interest focused on how to assess the rationales for conducting human genome projects, how to fund human genome projects (at what level and through which mechanisms), how to coordinate the scientific and technical programs of the several federal agencies and private interests already supporting various genome projects, and how to strike a balance regarding the impact of genome projects on international scientific cooperation and international economic competition in biotechnology. OTA prepared this report with the assistance of several hundred experts throughout the world. 342 refs., 26 figs., 11 tabs.

none,

1988-04-01

131

Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling  

Microsoft Academic Search

Treatment of pediatric acute lymphoblastic leukemia (ALL) is based on the concept of tailoring the intensity of therapy to a patient's risk of relapse. To determine whether gene expression profiling could enhance risk assignment, we used oligonucleotide microarrays to analyze the pattern of genes expressed in leukemic blasts from 360 pediatric ALL patients. Distinct expression profiles identified each of the

Eng-Juh Yeoh; Mary E. Ross; Sheila A. Shurtleff; W. Kent Williams; Divyen Patel; Rami Mahfouz; Fred G. Behm; Susana C. Raimondi; Mary V. Relling; Anami Patel; Cheng Cheng; Dario Campana; Dawn Wilkins; Xiaodong Zhou; Jinyan Li; Huiqing Liu; Ching-Hon Pui; William E Evans; Clayton Naeve; Limsoon Wong; James R Downing

2002-01-01

132

Systematic discovery of novel ciliary genes through functional genomics in the zebrafish  

PubMed Central

Cilia are microtubule-based hair-like organelles that play many important roles in development and physiology, and are implicated in a rapidly expanding spectrum of human diseases, collectively termed ciliopathies. Primary ciliary dyskinesia (PCD), one of the most prevalent of ciliopathies, arises from abnormalities in the differentiation or motility of the motile cilia. Despite their biomedical importance, a methodical functional screen for ciliary genes has not been carried out in any vertebrate at the organismal level. We sought to systematically discover novel motile cilia genes by identifying the genes induced by Foxj1, a winged-helix transcription factor that has an evolutionarily conserved role as the master regulator of motile cilia biogenesis. Unexpectedly, we find that the majority of the Foxj1-induced genes have not been associated with cilia before. To characterize these novel putative ciliary genes, we subjected 50 randomly selected candidates to a systematic functional phenotypic screen in zebrafish embryos. Remarkably, we find that over 60% are required for ciliary differentiation or function, whereas 30% of the proteins encoded by these genes localize to motile cilia. We also show that these genes regulate the proper differentiation and beating of motile cilia. This collection of Foxj1-induced genes will be invaluable for furthering our understanding of ciliary biology, and in the identification of new mutations underlying ciliary disorders in humans. PMID:25139857

Choksi, Semil P.; Babu, Deepak; Lau, Doreen; Yu, Xianwen; Roy, Sudipto

2014-01-01

133

Gene Discovery in Bladder Cancer Progression using cDNA Microarrays  

PubMed Central

To identify gene expression changes along progression of bladder cancer, we compared the expression profiles of early-stage and advanced bladder tumors using cDNA microarrays containing 17,842 known genes and expressed sequence tags. The application of bootstrapping techniques to hierarchical clustering segregated early-stage and invasive transitional carcinomas into two main clusters. Multidimensional analysis confirmed these clusters and more importantly, it separated carcinoma in situ from papillary superficial lesions and subgroups within early-stage and invasive tumors displaying different overall survival. Additionally, it recognized early-stage tumors showing gene profiles similar to invasive disease. Different techniques including standard t-test, single-gene logistic regression, and support vector machine algorithms were applied to identify relevant genes involved in bladder cancer progression. Cytokeratin 20, neuropilin-2, p21, and p33ING1 were selected among the top ranked molecular targets differentially expressed and validated by immunohistochemistry using tissue microarrays (n = 173). Their expression patterns were significantly associated with pathological stage, tumor grade, and altered retinoblastoma (RB) expression. Moreover, p33ING1 expression levels were significantly associated with overall survival. Analysis of the annotation of the most significant genes revealed the relevance of critical genes and pathways during bladder cancer progression, including the overexpression of oncogenic genes such as DEK in superficial tumors or immune response genes such as Cd86 antigen in invasive disease. Gene profiling successfully classified bladder tumors based on their progression and clinical outcome. The present study has identified molecular biomarkers of potential clinical significance and critical molecular targets associated with bladder cancer progression. PMID:12875971

Sanchez-Carbayo, Marta; Socci, Nicholas D.; Lozano, Juan Jose; Li, Wentian; Charytonowicz, Elizabeth; Belbin, Thomas J.; Prystowsky, Michael B.; Ortiz, Angel R.; Childs, Geoffrey; Cordon-Cardo, Carlos

2003-01-01

134

Discovery of estrogen receptor ? target genes and response elements in breast tumor cells  

PubMed Central

Background Estrogens and their receptors are important in human development, physiology and disease. In this study, we utilized an integrated genome-wide molecular and computational approach to characterize the interaction between the activated estrogen receptor (ER) and the regulatory elements of candidate target genes. Results Of around 19,000 genes surveyed in this study, we observed 137 ER-regulated genes in T-47D cells, of which only 89 were direct target genes. Meta-analysis of heterogeneous in vitro and in vivo datasets showed that the expression profiles in T-47D and MCF-7 cells are remarkably similar and overlap with genes differentially expressed between ER-positive and ER-negative tumors. Computational analysis revealed a significant enrichment of putative estrogen response elements (EREs) in the cis-regulatory regions of direct target genes. Chromatin immunoprecipitation confirmed ligand-dependent ER binding at the computationally predicted EREs in our highest ranked ER direct target genes, NRIP1, GREB1 and ABCA3. Wider examination of the cis-regulatory regions flanking the transcriptional start sites showed species conservation in mouse-human comparisons in only 6% of predicted EREs. Conclusions Only a small core set of human genes, validated across experimental systems and closely associated with ER status in breast tumors, appear to be sufficient to induce ER effects in breast cancer cells. That cis-regulatory regions of these core ER target genes are poorly conserved suggests that different evolutionary mechanisms are operative at transcriptional control elements than at coding regions. These results predict that certain biological effects of estrogen signaling will differ between mouse and human to a larger extent than previously thought. PMID:15345050

Lin, Chin-Yo; Ström, Anders; Vega, Vinsensius Berlian; Li Kong, Say; Li Yeo, Ai; Thomsen, Jane S; Chan, Wan Ching; Doray, Balraj; Bangarusamy, Dhinoth K; Ramasamy, Adaikalavan; Vergara, Liza A; Tang, Suisheng; Chong, Allen; Bajic, Vladimir B; Miller, Lance D; Gustafsson, Jan-Åke; Liu, Edison T

2004-01-01

135

Biochemical genomics for gene discovery in benzylisoquinoline alkaloid biosynthesis in opium poppy and related species.  

PubMed

Benzylisoquinoline alkaloids (BIAs) are a large, diverse group of ?2500 specialized plant metabolites. Many BIAs display potent pharmacological activities, including the narcotic analgesics codeine and morphine, the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine, the antimicrobial agents sanguinarine and berberine, and the muscle relaxant (+)-tubocurarine. Opium poppy remains the sole commercial source for codeine, morphine, and a variety of semisynthetic drugs, including oxycodone and buprenorphine, derived primarily from the biosynthetic pathway intermediate thebaine. Recent advances in transcriptomics, proteomics, and metabolomics have created unprecedented opportunities for isolating and characterizing novel BIA biosynthetic genes. Here, we describe the application of next-generation sequencing and cDNA microarrays for selecting gene candidates based on comparative transcriptome analysis. We outline the basic mass spectrometric techniques to perform deep proteome and targeted metabolite analyses on BIA-producing plant tissues and provide methodologies for functionally characterizing biosynthetic gene candidates through in vitro enzyme assays and transient gene silencing in planta. PMID:22999177

Dang, Thu Thuy T; Onoyovwi, Akpevwe; Farrow, Scott C; Facchini, Peter J

2012-01-01

136

Stanford discovery of gene fusion in ovarian cancer could lead to earlier diagnoses:  

Cancer.gov

About 15 percent of cases of an aggressive, difficult-to-detect form of ovarian cancer contain a unique fusion between two neighboring, normally separate genes, say researchers at the Stanford University School of Medicine.

137

Discovery of Candidate Genes for Muscle Traits Based on GWAS Supported by eQTL-analysis  

PubMed Central

Biochemical and biophysical processes that take place in muscle under relaxed and stressed conditions depend on the abundance and activity of gene products of metabolic and structural pathways. In livestock at post-mortem, these muscle properties determine aspects of meat quality and are measurable. The conversion of muscle to meat mimics pathological processes associated with muscle ischemia, injury or damage in humans and it is an economic factor in pork production. Linkage, association, and expression analyses independently contributed to the identification of trait-associated molecular pathways and genes. We aim at providing multiple evidences for the role of specific genes in meat quality by integrating a genome-wide association study (GWAS) for meat quality traits and the detection of eQTL based on trait-correlated expressed genes and trait-associated markers. The GWAS revealed 51 and 200 SNPs significantly associated with meat quality in a crossbred Pietrain×(German Landrace×Large White) (Pi×(GL×LW)) and a purebred German Landrace (GL) population, respectively. Most significant SNPs in Pi×(GL×LW) were located on chromosomes (SSC) 4 and 6. The data of 47,836 eQTLs at a significance level of p<10-5 were used to scale down the number candidate genes located in these regions. These SNPs on SSC4 showed association with expression levels of ZNF704, IMPA1, and OXSR1; SSC6 SNPs were associated with expression of SIGLEC10 and PIH1D1. Most significant SNPs in GL were located on SSC6 and associated with expression levels of PIH1D1, SIGLEC10, TBCB, LOC100518735, KIF1B, LOC100514845, and two unknown genes. The abundance of transcripts of these genes in muscle, in turn, is significantly correlated with meat quality traits. We identified several genes with evidence for their candidacy for meat quality arising from the integrative approach of a genome-wide association study and eQTL analysis. PMID:24643240

Ponsuksili, Siriluck; Murani, Eduard; Trakooljul, Nares; Schwerin, Manfred; Wimmers, Klaus

2014-01-01

138

Discovery of diversity in xylan biosynthetic genes by transcriptional profiling of a heteroxylan containing mucilaginous tissue  

PubMed Central

The exact biochemical steps of xylan backbone synthesis remain elusive. In Arabidopsis, three non-redundant genes from two glycosyltransferase (GT) families, IRX9 and IRX14 from GT43 and IRX10 from GT47, are candidates for forming the xylan backbone. In other plants, evidence exists that different tissues express these three genes at widely different levels, which suggests that diversity in the makeup of the xylan synthase complex exists. Recently we have profiled the transcripts present in the developing mucilaginous tissue of psyllium (Plantago ovata Forsk). This tissue was found to have high expression levels of an IRX10 homolog, but very low levels of the two GT43 family members. This contrasts with recent wheat endosperm tissue profiling that found a relatively high abundance of the GT43 family members. We have performed an in-depth analysis of all GTs genes expressed in four developmental stages of the psyllium mucilagenous layer and in a single stage of the psyllium stem using RNA-Seq. This analysis revealed several IRX10 homologs, an expansion in GT61 (homologs of At3g18170/At3g18180), and several GTs from other GT families that are highly abundant and specifically expressed in the mucilaginous tissue. Our current hypothesis is that the four IRX10 genes present in the mucilagenous tissues have evolved to function without the GT43 genes. These four genes represent some of the most divergent IRX10 genes identified to date. Conversely, those present in the psyllium stem are very similar to those in other eudicots. This suggests these genes are under selective pressure, likely due to the synthesis of the various xylan structures present in mucilage that has a different biochemical role than that present in secondary walls. The numerous GT61 family members also show a wide sequence diversity and may be responsible for the larger number of side chain structures present in the psyllium mucilage. PMID:23761806

Jensen, Jacob K.; Johnson, Nathan; Wilkerson, Curtis G.

2013-01-01

139

Transcriptome Analysis and Discovery of Genes Involved in Immune Pathways from Hepatopancreas of Microbial Challenged Mitten Crab Eriocheir sinensis  

PubMed Central

Background The Chinese mitten crab Eriocheir sinensis is an important economic crustacean and has been seriously attacked by various diseases, which requires more and more information for immune relevant genes on genome background. Recently, high-throughput RNA sequencing (RNA-seq) technology provides a powerful and efficient method for transcript analysis and immune gene discovery. Methods/Principal Findings A cDNA library from hepatopancreas of E. sinensis challenged by a mixture of three pathogen strains (Gram-positive bacteria Micrococcus luteus, Gram-negative bacteria Vibrio alginolyticus and fungi Pichia pastoris; 108 cfu·mL?1) was constructed and randomly sequenced using Illumina technique. Totally 39.76 million clean reads were assembled to 70,300 unigenes. After ruling out short-length and low-quality sequences, 52,074 non-redundant unigenes were compared to public databases for homology searching and 17,617 of them showed high similarity to sequences in NCBI non-redundant protein (Nr) database. For function classification and pathway assignment, 18,734 (36.00%) unigenes were categorized to three Gene Ontology (GO) categories, 12,243 (23.51%) were classified to 25 Clusters of Orthologous Groups (COG), and 8,983 (17.25%) were assigned to six Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Potentially, 24, 14, 47 and 132 unigenes were characterized to be involved in Toll, IMD, JAK-STAT and MAPK pathways, respectively. Conclusions/Significance This is the first systematical transcriptome analysis of components relating to innate immune pathways in E. sinensis. Functional genes and putative pathways identified here will contribute to better understand immune system and prevent various diseases in crab. PMID:23874555

Li, Xihong; Cui, Zhaoxia; Liu, Yuan; Song, Chengwen; Shi, Guohui

2013-01-01

140

De novo assembly of the common bean transcriptome using short reads for the discovery of drought-responsive genes.  

PubMed

The common bean (Phaseolus vulgaris L.) is one of the most important food legumes, far ahead of other legumes. The average grain yield of the common bean worldwide is much lower than its potential yields, primarily due to drought in the field. However, the gene network that mediates plant responses to drought stress remains largely unknown in this species. The major goals of our study are to identify a large scale of genes involved in drought stress using RNA-seq. First, we assembled 270 million high-quality trimmed reads into a non-redundant set of 62,828 unigenes, representing approximately 49 Mb of unique transcriptome sequences. Of these unigenes, 26,501 (42.2%) common bean unigenes had significant similarity with unigenes/predicted proteins from other legumes or sequenced plants. All unigenes were functionally annotated within the GO, COG and KEGG pathways. The strategy for de novo assembly of transcriptome data generated here will be useful in other legume plant transcriptome studies. Second, we identified 10,482 SSRs and 4,099 SNPs in transcripts. The large number of genetic markers provides a resource for gene discovery and development of functional molecular markers. Finally, we found differential expression genes (DEGs) between terminal drought and optimal irrigation treatments and between the two different genotypes Long 22-0579 (drought tolerant) and Naihua (drought sensitive). DEGs were confirmed by quantitative real-time PCR assays, which indicated that these genes are functionally associated with the drought-stress response. These resources will be helpful for basic and applied research for genome analysis and crop drought resistance improvement in the common bean. PMID:25275443

Wu, Jing; Wang, Lanfen; Li, Long; Wang, Shumin

2014-01-01

141

De Novo Assembly of the Common Bean Transcriptome Using Short Reads for the Discovery of Drought-Responsive Genes  

PubMed Central

The common bean (Phaseolus vulgaris L.) is one of the most important food legumes, far ahead of other legumes. The average grain yield of the common bean worldwide is much lower than its potential yields, primarily due to drought in the field. However, the gene network that mediates plant responses to drought stress remains largely unknown in this species. The major goals of our study are to identify a large scale of genes involved in drought stress using RNA-seq. First, we assembled 270 million high-quality trimmed reads into a non-redundant set of 62,828 unigenes, representing approximately 49 Mb of unique transcriptome sequences. Of these unigenes, 26,501 (42.2%) common bean unigenes had significant similarity with unigenes/predicted proteins from other legumes or sequenced plants. All unigenes were functionally annotated within the GO, COG and KEGG pathways. The strategy for de novo assembly of transcriptome data generated here will be useful in other legume plant transcriptome studies. Second, we identified 10,482 SSRs and 4,099 SNPs in transcripts. The large number of genetic markers provides a resource for gene discovery and development of functional molecular markers. Finally, we found differential expression genes (DEGs) between terminal drought and optimal irrigation treatments and between the two different genotypes Long 22-0579 (drought tolerant) and Naihua (drought sensitive). DEGs were confirmed by quantitative real-time PCR assays, which indicated that these genes are functionally associated with the drought-stress response. These resources will be helpful for basic and applied research for genome analysis and crop drought resistance improvement in the common bean. PMID:25275443

Wu, Jing; Wang, Lanfen; Li, Long; Wang, Shumin

2014-01-01

142

De Novo Assembly of Auricularia polytricha Transcriptome Using Illumina Sequencing for Gene Discovery and SSR Marker Identification  

PubMed Central

Auricularia polytricha (Mont.) Sacc., a type of edible black-brown mushroom with a gelatinous and modality-specific fruiting body, is in high demand in Asia due to its nutritional and medicinal properties. Illumina Solexa sequenceing technology was used to generate very large transcript sequences from the mycelium and the mature fruiting body of A. polytricha for gene discovery and molecular marker development. De novo assembly generated 36,483 ESTs with an N50 length of 636 bp. A total of 28,108 ESTs demonstrated significant hits with known proteins in the nr database, and 94.03% of the annotated ESTs showed the greatest similarity to A. delicata, a related species of A. polytricha. Functional categorization of the Gene Ontology (GO), Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed the conservation of genes involved in various biological processes in A. polytricha. Gene expression profile analysis indicated that a total of 2,057 ESTs were differentially expressed, including 1,020 ESTs that were up-regulated in the mycelium and 1,037 up-regulated in the fruiting body. Functional enrichment showed that the ESTs associated with biosynthesis, metabolism and assembly of proteins were more active in fruiting body development. The expression patterns of homologous transcription factors indicated that the molecular mechanisms of fruiting body formation and development were not exactly the same as for other agarics. Interestingly, an EST encoding tyrosinase was significantly up-regulated in the fruiting body, indicating that melanins accumulated during the processes of the formation of the black-brown color of the fruiting body in A. polytricha development. In addition, a total of 1,715 potential SSRs were detected in this transcriptome. The transcriptome analysis of A. polytricha provides valuable sequence resources and numerous molecular markers to facilitate further functional genomics studies and genetic researches on this fungus. PMID:24626227

Zhou, Yan; Chen, Lianfu; Fan, Xiuzhi; Bian, Yinbing

2014-01-01

143

Gene-expression-guided selection of candidate loci and molecular phenotype analyses enhance genetic discovery in systemic lupus erythematosus.  

PubMed

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disorder characterized by differences in autoantibody profiles, serum cytokines, and clinical manifestations. We have previously conducted a case-case genome-wide association study (GWAS) of SLE patients to detect associations with autoantibody profile and serum interferon alpha (IFN-?). In this study, we used public gene expression data sets to rationally select additional single nucleotide polymorphisms (SNPs) for validation. The top 200?GWAS SNPs were searched in a database which compares genome-wide expression data to genome-wide SNP genotype data in HapMap cell lines. SNPs were chosen for validation if they were associated with differential expression of 15 or more genes at a significance of P < 9 × 10(-5). This resulted in 11 SNPs which were genotyped in 453 SLE patients and 418 matched controls. Three SNPs were associated with SLE-associated autoantibodies, and one of these SNPs was also associated with serum IFN-? (P < 4.5 × 10(-3) for all). One additional SNP was associated exclusively with serum IFN-?. Case-control analysis was insensitive to these molecular subphenotype associations. This study illustrates the use of gene expression data to rationally select candidate loci in autoimmune disease, and the utility of stratification by molecular phenotypes in the discovery of additional genetic associations in SLE. PMID:22988468

Koldobskaya, Yelena; Ko, Kichul; Kumar, Akaash A; Agik, Sandra; Arrington, Jasmine; Kariuki, Silvia N; Franek, Beverly S; Kumabe, Marissa; Utset, Tammy O; Jolly, Meenakshi; Skol, Andrew D; Niewold, Timothy B

2012-01-01

144

Discovery and Characterization of Two Novel Salt-Tolerance Genes in Puccinellia tenuiflora  

PubMed Central

Puccinellia tenuiflora is a monocotyledonous halophyte that is able to survive in extreme saline soil environments at an alkaline pH range of 9–10. In this study, we transformed full-length cDNAs of P. tenuiflora into Saccharomyces cerevisiae by using the full-length cDNA over-expressing gene-hunting system to identify novel salt-tolerance genes. In all, 32 yeast clones overexpressing P. tenuiflora cDNA were obtained by screening under NaCl stress conditions; of these, 31 clones showed stronger tolerance to NaCl and were amplified using polymerase chain reaction (PCR) and sequenced. Four novel genes encoding proteins with unknown function were identified; these genes had no homology with genes from higher plants. Of the four isolated genes, two that encoded proteins with two transmembrane domains showed the strongest resistance to 1.3 M NaCl. RT-PCR and northern blot analysis of P. tenuiflora cultured cells confirmed the endogenous NaCl-induced expression of the two proteins. Both of the proteins conferred better tolerance in yeasts to high salt, alkaline and osmotic conditions, some heavy metals and H2O2 stress. Thus, we inferred that the two novel proteins might alleviate oxidative and other stresses in P. tenuiflora. PMID:25238412

Li, Ying; Takano, Tetsuo; Liu, Shenkui

2014-01-01

145

Discovery and characterization of two novel salt-tolerance genes in Puccinellia tenuiflora.  

PubMed

Puccinellia tenuiflora is a monocotyledonous halophyte that is able to survive in extreme saline soil environments at an alkaline pH range of 9-10. In this study, we transformed full-length cDNAs of P. tenuiflora into Saccharomyces cerevisiae by using the full-length cDNA over-expressing gene-hunting system to identify novel salt-tolerance genes. In all, 32 yeast clones overexpressing P. tenuiflora cDNA were obtained by screening under NaCl stress conditions; of these, 31 clones showed stronger tolerance to NaCl and were amplified using polymerase chain reaction (PCR) and sequenced. Four novel genes encoding proteins with unknown function were identified; these genes had no homology with genes from higher plants. Of the four isolated genes, two that encoded proteins with two transmembrane domains showed the strongest resistance to 1.3 M NaCl. RT-PCR and northern blot analysis of P. tenuiflora cultured cells confirmed the endogenous NaCl-induced expression of the two proteins. Both of the proteins conferred better tolerance in yeasts to high salt, alkaline and osmotic conditions, some heavy metals and H2O2 stress. Thus, we inferred that the two novel proteins might alleviate oxidative and other stresses in P. tenuiflora. PMID:25238412

Li, Ying; Takano, Tetsuo; Liu, Shenkui

2014-01-01

146

Designing and Developing a NASA Research Projects Knowledge Base and Implementing Knowledge Management and Discovery Techniques  

Microsoft Academic Search

The Research Project Knowledge Base (RPKB) is currently being designed and will be implemented in a manner that is fully compatible and interoperable with enterprise architecture tools developed to support NASA's Applied Sciences Program. Through user needs assessment, collaboration with Stennis Space Center, Goddard Space Flight Center, and NASA's DEVELOP Staff personnel insight to information needs for the RPKB were

L. Dabiru; C. G. O'Hara; D. Shaw; S. Katragadda; D. Anderson; S. Kim; B. Shrestha; J. Aanstoos; T. Frisbie; F. Policelli; N. Keblawi

2006-01-01

147

Human Genome Project discoveries: Dialectics and rhetoric in the science of genetics  

Microsoft Academic Search

The Human Genome Project (HGP), a $437 million effort that began in 1990 to chart the chemical sequence of our three billion base pairs of DNA, was completed in 2003, marking the 50th anniversary that proved the definitive structure of the molecule. This study considered how dialectical and rhetorical arguments functioned in the science, political, and public forums over a

Charlotte A. Robidoux

2008-01-01

148

Project ARCHIMEDES: Applications, Reasoning and Concepts for High School Instructors: Making Educational Discoveries and Expanding Skills.  

ERIC Educational Resources Information Center

Project ARCHIMEDES was designed in cooperation with local teachers to enhance concept understanding of teachers of physics and physical sciences, to increase use of electronics and computers in the classroom, and to introduce research on students' misconceptions in physics, teaching methods for identifying and remediating misconceptions, and ways…

Lea, Suzanne M.

149

Discovery of molecular mechanisms of traditional Chinese medicinal formula Si-Wu-Tang using gene expression microarray and connectivity map.  

PubMed

To pursue a systematic approach to discovery of mechanisms of action of traditional Chinese medicine (TCM), we used microarrays, bioinformatics and the "Connectivity Map" (CMAP) to examine TCM-induced changes in gene expression. We demonstrated that this approach can be used to elucidate new molecular targets using a model TCM herbal formula Si-Wu-Tang (SWT) which is widely used for women's health. The human breast cancer MCF-7 cells treated with 0.1 µM estradiol or 2.56 mg/ml of SWT showed dramatic gene expression changes, while no significant change was detected for ferulic acid, a known bioactive compound of SWT. Pathway analysis using differentially expressed genes related to the treatment effect identified that expression of genes in the nuclear factor erythroid 2-related factor 2 (Nrf2) cytoprotective pathway was most significantly affected by SWT, but not by estradiol or ferulic acid. The Nrf2-regulated genes HMOX1, GCLC, GCLM, SLC7A11 and NQO1 were upregulated by SWT in a dose-dependent manner, which was validated by real-time RT-PCR. Consistently, treatment with SWT and its four herbal ingredients resulted in an increased antioxidant response element (ARE)-luciferase reporter activity in MCF-7 and HEK293 cells. Furthermore, the gene expression profile of differentially expressed genes related to SWT treatment was used to compare with those of 1,309 compounds in the CMAP database. The CMAP profiles of estradiol-treated MCF-7 cells showed an excellent match with SWT treatment, consistent with SWT's widely claimed use for women's diseases and indicating a phytoestrogenic effect. The CMAP profiles of chemopreventive agents withaferin A and resveratrol also showed high similarity to the profiles of SWT. This study identified SWT as an Nrf2 activator and phytoestrogen, suggesting its use as a nontoxic chemopreventive agent, and demonstrated the feasibility of combining microarray gene expression profiling with CMAP mining to discover mechanisms of actions and to identify new health benefits of TCMs. PMID:21464939

Wen, Zhining; Wang, Zhijun; Wang, Steven; Ravula, Ranadheer; Yang, Lun; Xu, Jun; Wang, Charles; Zuo, Zhong; Chow, Moses S S; Shi, Leming; Huang, Ying

2011-01-01

150

Target genes discovery through copy number alteration analysis in human hepatocellular carcinoma.  

PubMed

High-throughput short-read sequencing of exomes and whole cancer genomes in multiple human hepatocellular carcinoma (HCC) cohorts confirmed previously identified frequently mutated somatic genes, such as TP53, CTNNB1 and AXIN1, and identified several novel genes with moderate mutation frequencies, including ARID1A, ARID2, MLL, MLL2, MLL3, MLL4, IRF2, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3, JAK1, KEAP1, NFE2L2, C16orf62, LEPR, RAC2, and IL6ST. Functional classification of these mutated genes suggested that alterations in pathways participating in chromatin remodeling, Wnt/?-catenin signaling, JAK/STAT signaling, and oxidative stress play critical roles in HCC tumorigenesis. Nevertheless, because there are few druggable genes used in HCC therapy, the identification of new therapeutic targets through integrated genomic approaches remains an important task. Because a large amount of HCC genomic data genotyped by high density single nucleotide polymorphism arrays is deposited in the public domain, copy number alteration (CNA) analyses of these arrays is a cost-effective way to reveal target genes through profiling of recurrent and overlapping amplicons, homozygous deletions and potentially unbalanced chromosomal translocations accumulated during HCC progression. Moreover, integration of CNAs with other high-throughput genomic data, such as aberrantly coding transcriptomes and non-coding gene expression in human HCC tissues and rodent HCC models, provides lines of evidence that can be used to facilitate the identification of novel HCC target genes with the potential of improving the survival of HCC patients. PMID:24379610

Gu, De-Leung; Chen, Yen-Hsieh; Shih, Jou-Ho; Lin, Chi-Hung; Jou, Yuh-Shan; Chen, Chian-Feng

2013-12-21

151

Target genes discovery through copy number alteration analysis in human hepatocellular carcinoma  

PubMed Central

High-throughput short-read sequencing of exomes and whole cancer genomes in multiple human hepatocellular carcinoma (HCC) cohorts confirmed previously identified frequently mutated somatic genes, such as TP53, CTNNB1 and AXIN1, and identified several novel genes with moderate mutation frequencies, including ARID1A, ARID2, MLL, MLL2, MLL3, MLL4, IRF2, ATM, CDKN2A, FGF19, PIK3CA, RPS6KA3, JAK1, KEAP1, NFE2L2, C16orf62, LEPR, RAC2, and IL6ST. Functional classification of these mutated genes suggested that alterations in pathways participating in chromatin remodeling, Wnt/?-catenin signaling, JAK/STAT signaling, and oxidative stress play critical roles in HCC tumorigenesis. Nevertheless, because there are few druggable genes used in HCC therapy, the identification of new therapeutic targets through integrated genomic approaches remains an important task. Because a large amount of HCC genomic data genotyped by high density single nucleotide polymorphism arrays is deposited in the public domain, copy number alteration (CNA) analyses of these arrays is a cost-effective way to reveal target genes through profiling of recurrent and overlapping amplicons, homozygous deletions and potentially unbalanced chromosomal translocations accumulated during HCC progression. Moreover, integration of CNAs with other high-throughput genomic data, such as aberrantly coding transcriptomes and non-coding gene expression in human HCC tissues and rodent HCC models, provides lines of evidence that can be used to facilitate the identification of novel HCC target genes with the potential of improving the survival of HCC patients. PMID:24379610

Gu, De-Leung; Chen, Yen-Hsieh; Shih, Jou-Ho; Lin, Chi-Hung; Jou, Yuh-Shan; Chen, Chian-Feng

2013-01-01

152

Genomic approaches for the discovery of genes mutated in inherited retinal degeneration.  

PubMed

In view of their high degree of genetic heterogeneity, inherited retinal diseases (IRDs) pose a significant challenge for identifying novel genetic causes. Thus far, more than 200 genes have been found to be mutated in IRDs, which together contain causal variants in >80% of the cases. Accurate genetic diagnostics is particularly important for isolated cases, in which X-linked and de novo autosomal dominant variants are not uncommon. In addition, new gene- or mutation-specific therapies are emerging, underlining the importance of identifying causative mutations in each individual. Sanger sequencing of selected genes followed by cost-effective targeted next-generation sequencing (NGS) can identify defects in known IRD-associated genes in the majority of the cases. Exome NGS in combination with genetic linkage or homozygosity mapping studies can aid the identification of the remaining causal genes. As these are thought to be mutated in <1% of the cases, validation through functional modeling in, for example, zebrafish and/or replication through the genotyping of large patient cohorts is required. In the near future, whole genome NGS in combination with transcriptome NGS may reveal mutations that are currently hidden in the noncoding regions of the human genome. PMID:24939053

Siemiatkowska, Anna M; Collin, Rob W J; den Hollander, Anneke I; Cremers, Frans P M

2014-08-01

153

Discovery of new regulatory genes of lipopeptide biosynthesis in Pseudomonas fluorescens.  

PubMed

Pseudomonas fluorescens SS101 produces the cyclic lipopeptide massetolide with diverse functions in antimicrobial activity, motility, and biofilm formation. To understand how massetolide biosynthesis is genetically regulated in SS101, c. 8000 random plasposon mutants were screened for reduced or loss of massetolide production. Of a total of 58 putative mutants, 45 had a mutation in one of the three massetolide biosynthesis genes massA, massB, or massC. For five mutants, the insertions were located in the known regulatory genes gacS, gacA, and clpP. For the remaining eight mutants, insertions were located in clpA, encoding the ClpP chaperone, in phgdh, encoding D-3-phosphoglycerate dehydrogenase, in the heat shock protein-encoding dnaK, or in the transmembrane regulatory gene prtR. Genetic, chemical, and phenotypic analyses showed that phgdh, dnaK, and prtR are indeed involved in the regulation of massetolide biosynthesis, most likely by transcriptional repression of the LuxR-type regulator genes massAR and massBCR. In addition to their role in massetolide biosynthesis, dnaK and prtR were found to affect siderophore and extracellular protease(s) production, respectively. The identification of new regulatory genes substantially extended insights into the signal transduction pathways of lipopeptide biosynthesis in P. fluorescens and into regulation of other traits that may contribute to its life-style in the rhizosphere. PMID:25202778

Song, Chunxu; Aundy, Kumar; van de Mortel, Judith; Raaijmakers, Jos M

2014-07-01

154

Integrating microRNA target predictions for the discovery of gene regulatory networks: a semi-supervised ensemble learning approach  

PubMed Central

Background MicroRNAs (miRNAs) are small non-coding RNAs which play a key role in the post-transcriptional regulation of many genes. Elucidating miRNA-regulated gene networks is crucial for the understanding of mechanisms and functions of miRNAs in many biological processes, such as cell proliferation, development, differentiation and cell homeostasis, as well as in many types of human tumors. To this aim, we have recently presented the biclustering method HOCCLUS2, for the discovery of miRNA regulatory networks. Experiments on predicted interactions revealed that the statistical and biological consistency of the obtained networks is negatively affected by the poor reliability of the output of miRNA target prediction algorithms. Recently, some learning approaches have been proposed to learn to combine the outputs of distinct prediction algorithms and improve their accuracy. However, the application of classical supervised learning algorithms presents two challenges: i) the presence of only positive examples in datasets of experimentally verified interactions and ii) unbalanced number of labeled and unlabeled examples. Results We present a learning algorithm that learns to combine the score returned by several prediction algorithms, by exploiting information conveyed by (only positively labeled/) validated and unlabeled examples of interactions. To face the two related challenges, we resort to a semi-supervised ensemble learning setting. Results obtained using miRTarBase as the set of labeled (positive) interactions and mirDIP as the set of unlabeled interactions show a significant improvement, over competitive approaches, in the quality of the predictions. This solution also improves the effectiveness of HOCCLUS2 in discovering biologically realistic miRNA:mRNA regulatory networks from large-scale prediction data. Using the miR-17-92 gene cluster family as a reference system and comparing results with previous experiments, we find a large increase in the number of significantly enriched biclusters in pathways, consistent with miR-17-92 functions. Conclusion The proposed approach proves to be fundamental for the computational discovery of miRNA regulatory networks from large-scale predictions. This paves the way to the systematic application of HOCCLUS2 for a comprehensive reconstruction of all the possible multiple interactions established by miRNAs in regulating the expression of gene networks, which would be otherwise impossible to reconstruct by considering only experimentally validated interactions. PMID:24564296

2014-01-01

155

Plant gravitropic signal transduction: A network analysis leads to gene discovery  

NASA Astrophysics Data System (ADS)

Gravity plays a fundamental role in plant growth and development. Although a significant body of research has helped define the events of gravity perception, the role of the plant growth regulator auxin, and the mechanisms resulting in the gravity response, the events of signal transduction, those that link the biophysical action of perception to a biochemical signal that results in auxin redistribution, those that regulate the gravitropic effects on plant growth, remain, for the most part, a “black box.” Using a cold affect, dubbed the gravity persistent signal (GPS) response, we developed a mutant screen to specifically identify components of the signal transduction pathway. Cloning of the GPS genes have identified new proteins involved in gravitropic signaling. We have further exploited the GPS response using a multi-faceted approach including gene expression microarrays, proteomics analysis, and bioinformatics analysis and continued mutant analysis to identified additional genes, physiological and biochemical processes. Gene expression data provided the foundation of a regulatory network for gravitropic signaling. Based on these gene expression data and related data sets/information from the literature/repositories, we constructed a gravitropic signaling network for Arabidopsis inflorescence stems. To generate the network, both a dynamic Bayesian network approach and a time-lagged correlation coefficient approach were used. The dynamic Bayesian network added existing information of protein-protein interaction while the time-lagged correlation coefficient allowed incorporation of temporal regulation and thus could incorporate the time-course metric from the data set. Thus the methods complemented each other and provided us with a more comprehensive evaluation of connections. Each method generated a list of possible interactions associated with a statistical significance value. The two networks were then overlaid to generate a more rigorous, intersected network with shared genes and interactions. This network is flexible and can be updated with new data from the original research. The network allows identification of hubs/additional components and processes that are involved in gravitropic signal transduction to provide further hypotheses for testing. In essence, genes identified through experimental methods can be located and interactions that might connect them identified. Genes along these connections can then tested, much like stopping at towns along a driving route from one city to another.

Wyatt, Sarah

156

The discovery of the two types of small subunit ribosomal RNA gene in Eimeria mitis contests the existence of E. mivati as an independent species  

Microsoft Academic Search

Although the validity of the coccidian species, Eimeria mivati, has been questioned by many researchers for a long time there has not been any molecular analysis that would help resolve this issue. Here we report on the discovery of the two types of small ribosomal subunit (18S) gene within the Eimeria mitis genome that correspond to the known 18S sequences

Vladimir Vrba; Martin Poplstein; Michal Pakandl

157

Transcriptome analysis of Catharanthus roseus for gene discovery and expression profiling.  

PubMed

The medicinal plant, Catharanthus roseus, accumulates wide range of terpenoid indole alkaloids, which are well documented therapeutic agents. In this study, deep transcriptome sequencing of C. roseus was carried out to identify the pathways and enzymes (genes) involved in biosynthesis of these compounds. About 343 million reads were generated from different tissues (leaf, flower and root) of C. roseus using Illumina platform. Optimization of de novo assembly involving a two-step process resulted in a total of 59,220 unique transcripts with an average length of 1284 bp. Comprehensive functional annotation and gene ontology (GO) analysis revealed the representation of many genes involved in different biological processes and molecular functions. In total, 65% of C. roseus transcripts showed homology with sequences available in various public repositories, while remaining 35% unigenes may be considered as C. roseus specific. In silico analysis revealed presence of 11,620 genic simple sequence repeats (excluding mono-nucleotide repeats) and 1820 transcription factor encoding genes in C. roseus transcriptome. Expression analysis showed roots and leaves to be actively participating in bisindole alkaloid production with clear indication that enzymes involved in pathway of vindoline and vinblastine biosynthesis are restricted to aerial tissues. Such large-scale transcriptome study provides a rich source for understanding plant-specialized metabolism, and is expected to promote research towards production of plant-derived pharmaceuticals. PMID:25072156

Verma, Mohit; Ghangal, Rajesh; Sharma, Raghvendra; Sinha, Alok K; Jain, Mukesh

2014-01-01

158

Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome  

Microsoft Academic Search

Human brain connectivity is disrupted in a wide range of disorders — from Alzheimer's disease to autism — but little is known about which specific genes affect it. Here we conducted a genome-wide association for connectivity matrices that capture information on the density of fiber connections between 70 brain regions. We scanned a large twin cohort (N=366) with 4-Tesla high

Neda Jahanshad; Derrek P. Hibar; April Ryles; Arthur W. Toga; Katie L. McMahon; Greig I. de Zubicaray; Narelle K. Hansell; Grant W. Montgomery; Nicholas G. Martin; Margaret J. Wright; Paul M. Thompson

2012-01-01

159

Use of eQTL Analysis for the Discovery of Target Genes Identified by GWAS.  

National Technical Information Service (NTIS)

The goals of this grant proposal are to: (1) construct a prostate tissue-specific expression quantitative trait loci (eQTL) dataset; and (2) utilize this dataset to identify candidate genes for existing prostate cancer (PC) risk-single nucleotide polymorp...

S. Thibodeau

2012-01-01

160

Discovery and assessment of conserved Pax6 target genes and enhancers  

PubMed Central

The characterization of transcriptional networks (TNs) is essential for understanding complex biological phenomena such as development, disease, and evolution. In this study, we have designed and implemented a procedure that combines in silico target screens with zebrafish and mouse validation, in order to identify cis-elements and genes directly regulated by Pax6. We chose Pax6 as the paradigm because of its crucial roles in organogenesis and human disease. We identified over 600 putative Pax6 binding sites and more than 200 predicted direct target genes, conserved in evolution from zebrafish to human and to mouse. This was accomplished using hidden Markov models (HMMs) generated from experimentally validated Pax6 binding sites. A small sample of genes, expressed in the neural lineage, was chosen from the predictions for RNA in situ validation using zebrafish and mouse models. Validation of DNA binding to some predicted cis-elements was also carried out using chromatin immunoprecipitation (ChIP) and zebrafish reporter transgenic studies. The results show that this combined procedure is a highly efficient tool to investigate the architecture of TNs and constitutes a useful complementary resource to ChIP and expression data sets because of its inherent spatiotemporal independence. We have identified several novel direct targets, including some putative disease genes, among them Foxp2; these will allow further dissection of Pax6 function in development and disease. PMID:21617155

Coutinho, Pedro; Pavlou, Sofia; Bhatia, Shipra; Chalmers, Kevin J.; Kleinjan, Dirk A.; van Heyningen, Veronica

2011-01-01

161

Discovery and functional assessment of gene variants in the vascular endothelial growth factor pathway.  

PubMed

Angiogenesis is a host-mediated mechanism in disease pathophysiology. The vascular endothelial growth factor (VEGF) pathway is a major determinant of angiogenesis, and a comprehensive annotation of the functional variation in this pathway is essential to understand the genetic basis of angiogenesis-related diseases. We assessed the allelic heterogeneity of gene expression, population specificity of cis expression quantitative trait loci (eQTLs), and eQTL function in luciferase assays in CEU and Yoruba people of Ibadan, Nigeria (YRI) HapMap lymphoblastoid cell lines in 23 resequenced genes. Among 356 cis-eQTLs, 155 and 174 were unique to CEU and YRI, respectively, and 27 were shared between CEU and YRI. Two cis-eQTLs provided mechanistic evidence for two genome-wide association study findings. Five eQTLs were tested for function in luciferase assays and the effect of two KRAS variants was concordant with the eQTL effect. Two eQTLs found in each of PRKCE, PIK3C2A, and MAP2K6 could predict 44%, 37%, and 45% of the variance in gene expression, respectively. This is the first analysis focusing on the pattern of functional genetic variation of the VEGF pathway genes in CEU and YRI populations and providing mechanistic evidence for genetic association studies of diseases for which angiogenesis plays a pathophysiologic role. PMID:24186849

Paré-Brunet, Laia; Glubb, Dylan; Evans, Patrick; Berenguer-Llergo, Antoni; Etheridge, Amy S; Skol, Andrew D; Di Rienzo, Anna; Duan, Shiwei; Gamazon, Eric R; Innocenti, Federico

2014-02-01

162

Gene Annotation and Drug Target Discovery in Candida albicans with a Tagged Transposon Mutant Collection  

Microsoft Academic Search

Candida albicans is the most common human fungal pathogen, causing infections that can be lethal in immunocompromised patients. Although Saccharomyces cerevisiae has been used as a model for C. albicans, it lacks C. albicans' diverse morphogenic forms and is primarily non-pathogenic. Comprehensive genetic analyses that have been instrumental for determining gene function in S. cerevisiae are hampered in C. albicans,

Julia Oh; Eula Fung; Ulrich Schlecht; Ronald W. Davis; Guri Giaever; Robert P. St. Onge; Adam Deutschbauer; Corey Nislow

2010-01-01

163

Human Transporter Database: Comprehensive Knowledge and Discovery Tools in the Human Transporter Genes  

PubMed Central

Transporters are essential in homeostatic exchange of endogenous and exogenous substances at the systematic, organic, cellular, and subcellular levels. Gene mutations of transporters are often related to pharmacogenetics traits. Recent developments in high throughput technologies on genomics, transcriptomics and proteomics allow in depth studies of transporter genes in normal cellular processes and diverse disease conditions. The flood of high throughput data have resulted in urgent need for an updated knowledgebase with curated, organized, and annotated human transporters in an easily accessible way. Using a pipeline with the combination of automated keywords query, sequence similarity search and manual curation on transporters, we collected 1,555 human non-redundant transporter genes to develop the Human Transporter Database (HTD) (http://htd.cbi.pku.edu.cn). Based on the extensive annotations, global properties of the transporter genes were illustrated, such as expression patterns and polymorphisms in relationships with their ligands. We noted that the human transporters were enriched in many fundamental biological processes such as oxidative phosphorylation and cardiac muscle contraction, and significantly associated with Mendelian and complex diseases such as epilepsy and sudden infant death syndrome. Overall, HTD provides a well-organized interface to facilitate research communities to search detailed molecular and genetic information of transporters for development of personalized medicine. PMID:24558441

Ye, Adam Y.; Liu, Qing-Rong; Li, Chuan-Yun; Zhao, Min; Qu, Hong

2014-01-01

164

Molecular mapping of soybean rust (Phakopsora pachyrhizi) resistance genes: discovery of a novel locus and alleles.  

PubMed

Soybean production in South and North America has recently been threatened by the widespread dissemination of soybean rust (SBR) caused by the fungus Phakopsora pachyrhizi. Currently, chemical spray containing fungicides is the only effective method to control the disease. This strategy increases production costs and exposes the environment to higher levels of fungicides. As a first step towards the development of SBR resistant cultivars, we studied the genetic basis of SBR resistance in five F2 populations derived from crossing the Brazilian-adapted susceptible cultivar CD 208 to each of five different plant introductions (PI 200487, PI 200526, PI 230970, PI 459025, PI 471904) carrying SBR-resistant genes (Rpp). Molecular mapping of SBR-resistance genes was performed in three of these PIs (PI 459025, PI 200526, PI 471904), and also in two other PIs (PI 200456 and 224270). The strategy mapped two genes present in PI 230970 and PI 459025, the original sources of Rpp2 and Rpp4, to linkage groups (LG) J and G, respectively. A new SBR resistance locus, rpp5 was mapped in the LG-N. Together, the genetic and molecular analysis suggested multiple alleles or closely linked genes that govern SBR resistance in soybean. PMID:18506417

Garcia, Alexandre; Calvo, Eberson Sanches; de Souza Kiihl, Romeu Afonso; Harada, Arlindo; Hiromoto, Dario Minoru; Vieira, Luiz Gonzaga Esteves

2008-08-01

165

The Extragalactic Distance Scale Key Project VIII. The Discovery of Cepheids and a New Distance to NGC 3621 Using the Hubble Space Telescope  

NASA Technical Reports Server (NTRS)

We report on the discovery of Cepheids in the field spiral galaxy NGC3621, based on observations made with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope (HST). NGC 3621 is one of 18 galaxies observed as part of the HST Key Project on the Extragalctic Distance Scale, which aims to measure the Hubble Constant to 10 percent accuracy.

Rawson, D. M.; Mould, J. R.; Macri, L. M.; Huchra, J. P.; Kennicutt, R. C.; Harding, P.; Freedman, W. L.; Hill, R. J.; Phelps, R. L.; Madore, B. F.; Silbermann, N. A.; Graham, J. A.; Ferrarese, L.; Ford, H. C.; Illingworth, G. D.; Hoessel, J. G.; Han, M.; Hughes, S. M.; Saha, A.; Stetson, P. B.

1996-01-01

166

The human gene connectome as a map of short cuts for morbid allele discovery  

PubMed Central

High-throughput genomic data reveal thousands of gene variants per patient, and it is often difficult to determine which of these variants underlies disease in a given individual. However, at the population level, there may be some degree of phenotypic homogeneity, with alterations of specific physiological pathways underlying the pathogenesis of a particular disease. We describe here the human gene connectome (HGC) as a unique approach for human Mendelian genetic research, facilitating the interpretation of abundant genetic data from patients with the same disease, and guiding subsequent experimental investigations. We first defined the set of the shortest plausible biological distances, routes, and degrees of separation between all pairs of human genes by applying a shortest distance algorithm to the full human gene network. We then designed a hypothesis-driven application of the HGC, in which we generated a Toll-like receptor 3-specific connectome useful for the genetic dissection of inborn errors of Toll-like receptor 3 immunity. In addition, we developed a functional genomic alignment approach from the HGC. In functional genomic alignment, the genes are clustered according to biological distance (rather than the traditional molecular evolutionary genetic distance), as estimated from the HGC. Finally, we compared the HGC with three state-of-the-art methods: String, FunCoup, and HumanNet. We demonstrated that the existing methods are more suitable for polygenic studies, whereas HGC approaches are more suitable for monogenic studies. The HGC and functional genomic alignment data and computer programs are freely available to noncommercial users from http://lab.rockefeller.edu/casanova/HGC and should facilitate the genome-wide selection of disease-causing candidate alleles for experimental validation. PMID:23509278

Itan, Yuval; Zhang, Shen-Ying; Vogt, Guillaume; Abhyankar, Avinash; Herman, Melina; Nitschke, Patrick; Fried, Dror; Quintana-Murci, Lluis; Abel, Laurent; Casanova, Jean-Laurent

2013-01-01

167

The MY NASA DATA Project: Tools and a Collaboration Space for Knowledge Discovery  

NASA Astrophysics Data System (ADS)

The Atmospheric Science Data Center (ASDC) at NASA Langley Research Center is charged with serving a wide user community that is interested in its large data holdings in the areas of Aerosols, Clouds, Radiation Budget, and Tropospheric Chemistry. Most of the data holdings, however, are in large files with specialized data formats. The MY NASA DATA (mynasadata.larc.nasa.gov) project began in 2004, as part of the NASA Research, Education, and Applications Solutions Network (REASoN), in order to open this important resource to a broader community including K-12 education and citizen scientists. MY NASA DATA (short for Mentoring and inquirY using NASA Data on Atmospheric and earth science for Teachers and Amateurs) consists of a web space that collects tools, lesson plans, and specially developed documentation to help the target audience more easily use the vast collection of NASA data about the Earth System. The core piece of the MY NASA DATA project is the creation of microsets (both static and custom) that make data easily accessible. The installation of a Live Access Server (LAS) greatly enhanced the ability for teachers, students, and citizen scientists to create and explore custom microsets of Earth System Science data. The LAS, which is an open source software tool using emerging data standards, also allows the MY NASA DATA team to make available data on other aspects of the Earth System from collaborating data centers. We are currently working with the Physical Oceanography DAAC at the Jet Propulsion Laboratory to bring in several parameters describing the ocean. In addition, MY NASA DATA serves as a central space for the K-12 community to share resources. The site already includes a dozen User-contributed lesson plans. This year we will be focusing on the Citizen Science portion of the site, and will be welcoming user-contributed project ideas, as well as reports of completed projects. An e-mentor network has also been created to involve a wider community in answering questions on scientific and pedagogical aspects of data use. The MY NASA DATA website, and an initial collection of lesson plans, have passed the NASA Earth Science Education peer review process, and thus are also being cataloged in the Digital Library for Earth System Education (DLESE).

Chambers, L. H.; Alston, E. J.; Diones, D. D.; Moore, S. W.; Oots, P. C.; Phelps, C. S.

2006-05-01

168

A Systems-Genetics Approach and Data Mining Tool to Assist in the Discovery of Genes Underlying Complex Traits in Oryza sativa  

PubMed Central

Many traits of biological and agronomic significance in plants are controlled in a complex manner where multiple genes and environmental signals affect the expression of the phenotype. In Oryza sativa (rice), thousands of quantitative genetic signals have been mapped to the rice genome. In parallel, thousands of gene expression profiles have been generated across many experimental conditions. Through the discovery of networks with real gene co-expression relationships, it is possible to identify co-localized genetic and gene expression signals that implicate complex genotype-phenotype relationships. In this work, we used a knowledge-independent, systems genetics approach, to discover a high-quality set of co-expression networks, termed Gene Interaction Layers (GILs). Twenty-two GILs were constructed from 1,306 Affymetrix microarray rice expression profiles that were pre-clustered to allow for improved capture of gene co-expression relationships. Functional genomic and genetic data, including over 8,000 QTLs and 766 phenotype-tagged SNPs (p-value GeneNet Engine, was constructed to enable dynamic discovery of gene sets (i.e. network modules) that overlap with genetic traits. GeneNet Engine does not provide the exact set of genes underlying a given complex trait, but through the evidence of gene-marker correspondence, co-expression, and functional enrichment, site visitors can identify genes with potential shared causality for a trait which could then be used for experimental validation. A set of 2 million SNPs was incorporated into the database and serve as a potential set of testable biomarkers for genes in modules that overlap with genetic traits. Herein, we describe two modules found using GeneNet Engine, one with significant overlap with the trait amylose content and another with significant overlap with blast disease resistance. PMID:23874666

Ficklin, Stephen P.; Feltus, Frank Alex

2013-01-01

169

Beyond gene discovery in inflammatory bowel disease: the emerging role of epigenetics.  

PubMed

In the past decade, there have been fundamental advances in our understanding of genetic factors that contribute to the inflammatory bowel diseases (IBDs) Crohn's disease and ulcerative colitis. The latest international collaborative studies have brought the number of IBD susceptibility gene loci to 163. However, genetic factors account for only a portion of overall disease variance, indicating a need to better explore gene-environment interactions in the development of IBD. Epigenetic factors can mediate interactions between the environment and the genome; their study could provide new insight into the pathogenesis of IBD. We review recent progress in identification of genetic factors associated with IBD and discuss epigenetic mechanisms that could affect development and progression of IBD. PMID:23751777

Ventham, Nicholas T; Kennedy, Nicholas A; Nimmo, Elaine R; Satsangi, Jack

2013-08-01

170

Beyond Gene Discovery in Inflammatory Bowel Disease: The Emerging Role of Epigenetics  

PubMed Central

In the past decade, there have been fundamental advances in our understanding of genetic factors that contribute to the inflammatory bowel diseases (IBDs) Crohn’s disease and ulcerative colitis. The latest international collaborative studies have brought the number of IBD susceptibility gene loci to 163. However, genetic factors account for only a portion of overall disease variance, indicating a need to better explore gene-environment interactions in the development of IBD. Epigenetic factors can mediate interactions between the environment and the genome; their study could provide new insight into the pathogenesis of IBD. We review recent progress in identification of genetic factors associated with IBD and discuss epigenetic mechanisms that could affect development and progression of IBD. PMID:23751777

Ventham, Nicholas T.; Kennedy, Nicholas A.; Nimmo, Elaine R.; Satsangi, Jack

2013-01-01

171

SAM Thresholding and False Discovery Rates for Detecting Differential Gene Expression in DNA Microarrays  

Microsoft Academic Search

SAM is a computer package for correlating gene expression with an outcome parameter such as treatment, survival time, or diagnostic class. It thresholds an appropriate test statistic and reports the q-value of each test based on a set of sample permutations. SAM works as a Microsoft Excel add-in and has additional features for fold-change thresholding and block permutations. Here, we

John D. Storey; Robert Tibshirani

172

Discovery of Nuclear-Encoded Genes for the Neurotoxin Saxitoxin in Dinoflagellates  

PubMed Central

Saxitoxin is a potent neurotoxin that occurs in aquatic environments worldwide. Ingestion of vector species can lead to paralytic shellfish poisoning, a severe human illness that may lead to paralysis and death. In freshwaters, the toxin is produced by prokaryotic cyanobacteria; in marine waters, it is associated with eukaryotic dinoflagellates. However, several studies suggest that saxitoxin is not produced by dinoflagellates themselves, but by co-cultured bacteria. Here, we show that genes required for saxitoxin synthesis are encoded in the nuclear genomes of dinoflagellates. We sequenced >1.2×106 mRNA transcripts from the two saxitoxin-producing dinoflagellate strains Alexandrium fundyense CCMP1719 and A. minutum CCMP113 using high-throughput sequencing technology. In addition, we used in silico transcriptome analyses, RACE, qPCR and conventional PCR coupled with Sanger sequencing. These approaches successfully identified genes required for saxitoxin-synthesis in the two transcriptomes. We focused on sxtA, the unique starting gene of saxitoxin synthesis, and show that the dinoflagellate transcripts of sxtA have the same domain structure as the cyanobacterial sxtA genes. But, in contrast to the bacterial homologs, the dinoflagellate transcripts are monocistronic, have a higher GC content, occur in multiple copies, contain typical dinoflagellate spliced-leader sequences and eukaryotic polyA-tails. Further, we investigated 28 saxitoxin-producing and non-producing dinoflagellate strains from six different genera for the presence of genomic sxtA homologs. Our results show very good agreement between the presence of sxtA and saxitoxin-synthesis, except in three strains of A. tamarense, for which we amplified sxtA, but did not detect the toxin. Our work opens for possibilities to develop molecular tools to detect saxitoxin-producing dinoflagellates in the environment. PMID:21625593

Stuken, Anke; Orr, Russell J. S.; Kellmann, Ralf; Murray, Shauna A.; Neilan, Brett A.; Jakobsen, Kjetill S.

2011-01-01

173

Adenovirus vector library: an approach to the discovery of gene and protein function  

Microsoft Academic Search

A method was developed to generate a complex cDNA expression library within an adenovirus type 5 (Ad5)-based vector backbone, termed AdLibrary. Construction of the AdLibrary entailed the conversion of an Ad5 genome-containing cosmid to infectious virus particles. The Ad5 genome was modified by replacing the E1A and E1B genes with a Rous sarcoma virus-driven expression cassette. Conversion was accomplished by

Duncan McVey; Mohammed Zuber; Douglas E. Brough; Imre Kovesdi

2003-01-01

174

Meta-analysis discovery of tissue-specific DNA sequence motifs from mammalian gene expression data  

PubMed Central

Background A key step in the regulation of gene expression is the sequence-specific binding of transcription factors (TFs) to their DNA recognition sites. However, elucidating TF binding site (TFBS) motifs in higher eukaryotes has been challenging, even when employing cross-species sequence conservation. We hypothesized that for human and mouse, many orthologous genes expressed in a similarly tissue-specific manner in both human and mouse gene expression data, are likely to be co-regulated by orthologous TFs that bind to DNA sequence motifs present within noncoding sequence conserved between these genomes. Results We performed automated motif searching and merging across four different motif finding algorithms, followed by filtering of the resulting motifs for those that contain blocks of information content. Applying this motif finding strategy to conserved noncoding regions surrounding co-expressed tissue-specific human genes allowed us to discover both previously known, and many novel candidate, regulatory DNA motifs in all 18 tissue-specific expression clusters that we examined. For previously known TFBS motifs, we observed that if a TF was expressed in the specified tissue of interest, then in most cases we identified a motif that matched its TRANSFAC motif; conversely, of all those discovered motifs that matched TRANSFAC motifs, most of the corresponding TF transcripts were expressed in the tissue(s) corresponding to the expression cluster for which the motif was found. Conclusion Our results indicate that the integration of the results from multiple motif finding tools identifies and ranks highly more known and novel motifs than does the use of just one of these tools. In addition, we believe that our simultaneous enrichment strategies helped to identify likely human cis regulatory elements. A number of the discovered motifs may correspond to novel binding site motifs for as yet uncharacterized tissue-specific TFs. We expect this strategy to be useful for identifying motifs in other metazoan genomes. PMID:16643658

Huber, Bertrand R; Bulyk, Martha L

2006-01-01

175

Gene Discovery through Transcriptome Sequencing for the Invasive Mussel Limnoperna fortunei  

PubMed Central

The success of the Asian bivalve Limnoperna fortunei as an invader in South America is related to its high acclimation capability. It can inhabit waters with a wide range of temperatures and salinity and handle long-term periods of air exposure. We describe the transcriptome of L. fortunei aiming to give a first insight into the phenotypic plasticity that allows non-native taxa to become established and widespread. We sequenced 95,219 reads from five main tissues of the mussel L. fortunei using Roche’s 454 and assembled them to form a set of 84,063 unigenes (contigs and singletons) representing partial or complete gene sequences. We annotated 24,816 unigenes using a BLAST sequence similarity search against a NCBI nr database. Unigenes were divided into 20 eggNOG functional categories and 292 KEGG metabolic pathways. From the total unigenes, 1,351 represented putative full-length genes of which 73.2% were functionally annotated. We described the first partial and complete gene sequences in order to start understanding bivalve invasiveness. An expansion of the hsp70 gene family, seen also in other bivalves, is present in L. fortunei and could be involved in its adaptation to extreme environments, e.g. during intertidal periods. The presence of toll-like receptors gives a first insight into an immune system that could be more complex than previously assumed and may be involved in the prevention of disease and extinction when population densities are high. Finally, the apparent lack of special adaptations to extremely low O2 levels is a target worth pursuing for the development of a molecular control approach. PMID:25047650

Uliano-Silva, Marcela; Americo, Juliana Alves; Brindeiro, Rodrigo; Dondero, Francesco; Prosdocimi, Francisco; de Freitas Rebelo, Mauro

2014-01-01

176

FMR1, circadian genes and depression: suggestive associations or false discovery?  

PubMed Central

Background There are several indications that malfunctions of the circadian clock contribute to depression. To search for particular circadian gene polymorphisms associated with depression, diverse polymorphisms were genotyped in two samples covering a range of depressed volunteers and participants with normal mood. Methods Depression mood self-ratings and DNA were collected independently from a sample of patients presenting to a sleep disorders center (1086 of European origin) and from a separate sample consisting of 399 participants claiming delayed sleep phase symptoms and 406 partly-matched controls. A custom Illumina Golden Gate array of 768 selected single nucleotide polymorphisms (SNPs) was assayed in both samples, supplemented by additional SNPlex and Taqman assays, including assay of 41 ancestry-associated markers (AIMs) to control stratification. Results In the Sleep Clinic sample, these assays yielded Bonferroni-significant association with depressed mood in three linked SNPs of the gene FMR1: rs25702 (nominal P=1.77E-05), rs25714 (P=1.83E-05), and rs28900 (P=5.24E-05). This FMR1 association was supported by 8 SNPs with nominal significance and a nominally-significant gene-wise set test. There was no association of depressed mood with FMR1 in the delayed sleep phase case–control sample or in downloaded GWAS data from the GenRED 2 sample contrasting an early-onset recurrent depression sample with controls. No replication was located in other GWAS studies of depression. Our data did weakly replicate a previously-reported association of depression with PPARGC1B rs7732671 (P=0.0235). Suggestive associations not meeting strict criteria for multiple testing and replication were found with GSK3B, NPAS2, RORA, PER3, CRY1, MTNR1A and NR1D1. Notably, 16 SNPs nominally associated with depressed mood (14 in GSK3B) were also nominally associated with delayed sleep phase syndrome (P=3E10-6). Conclusions Considering the inconsistencies between samples and the likelihood that the significant three FMR1 SNPs might be linked to complex polymorphisms more functionally related to depression, large gene resequencing studies may be needed to clarify the import for depression of these circadian genes. PMID:23521777

2013-01-01

177

Gene Discovery and Molecular Marker Development, Based on High-Throughput Transcript Sequencing of Paspalum dilatatum Poir  

PubMed Central

Background Paspalum dilatatum Poir. (common name dallisgrass) is a native grass species of South America, with special relevance to dairy and red meat production. P. dilatatum exhibits higher forage quality than other C4 forage grasses and is tolerant to frost and water stress. This species is predominantly cultivated in an apomictic monoculture, with an inherent high risk that biotic and abiotic stresses could potentially devastate productivity. Therefore, advanced breeding strategies that characterise and use available genetic diversity, or assess germplasm collections effectively are required to deliver advanced cultivars for production systems. However, there are limited genomic resources available for this forage grass species. Results Transcriptome sequencing using second-generation sequencing platforms has been employed using pooled RNA from different tissues (stems, roots, leaves and inflorescences) at the final reproductive stage of P. dilatatum cultivar Primo. A total of 324,695 sequence reads were obtained, corresponding to c. 102 Mbp. The sequences were assembled, generating 20,169 contigs of a combined length of 9,336,138 nucleotides. The contigs were BLAST analysed against the fully sequenced grass species of Oryza sativa subsp. japonica, Brachypodium distachyon, the closely related Sorghum bicolor and foxtail millet (Setaria italica) genomes as well as against the UniRef 90 protein database allowing a comprehensive gene ontology analysis to be performed. The contigs generated from the transcript sequencing were also analysed for the presence of simple sequence repeats (SSRs). A total of 2,339 SSR motifs were identified within 1,989 contigs and corresponding primer pairs were designed. Empirical validation of a cohort of 96 SSRs was performed, with 34% being polymorphic between sexual and apomictic biotypes. Conclusions The development of genetic and genomic resources for P. dilatatum will contribute to gene discovery and expression studies. Association of gene function with agronomic traits will significantly enable molecular breeding and advance germplasm enhancement. PMID:24520314

Giordano, Andrea; Cogan, Noel O. I.; Kaur, Sukhjiwan; Drayton, Michelle; Mouradov, Aidyn; Panter, Stephen; Schrauf, Gustavo E.; Mason, John G.; Spangenberg, German C.

2014-01-01

178

Transcriptome analysis of head kidney in grass carp and discovery of immune-related genes  

PubMed Central

Background Grass carp (Ctenopharyngodon idella) is one of the most economically important freshwater fish, but its production is often affected by diseases that cause serious economic losses. To date, no good breeding varieties have been obtained using the oriented cultivation technique. The ability to identify disease resistance genes in grass carp is important to cultivate disease-resistant varieties of grass carp. Results In this study, we constructed a non-normalized cDNA library of head kidney in grass carp, and, after clustering and assembly, we obtained 3,027 high-quality unigenes. Solexa sequencing was used to generate sequence tags from the transcriptomes of the head kidney in grass carp before and after grass carp reovirus (GCRV) infection. After processing, we obtained 22,144 tags that were differentially expressed by more than 2-fold between the uninfected and infected groups. 679 of the differentially expressed tags (3.1%) mapped to 483 of the unigenes (16.0%). The up-regulated and down-regulated unigenes were annotated using gene ontology terms; 16 were annotated as immune-related and 42 were of unknown function having no matches to any of the sequences in the databases that were used in the similarity searches. Semi-quantitative RT-PCR revealed four unknown unigenes that showed significant responses to the viral infection. Based on domain structure predictions, one of these sequences was found to encode a protein that contained two transmembrane domains and, therefore, may be a transmembrane protein. Here, we proposed that this novel unigene may encode a virus receptor or a protein that mediates the immune signalling pathway at the cell surface. Conclusion This study enriches the molecular basis data of grass carp and further confirms that, based on fish tissue-specific EST databases, transcriptome analysis is an effective route to discover novel functional genes. PMID:22776770

2012-01-01

179

Functional Analysis and Discovery of Microbial Genes Transforming Metallic and Organic Pollutants: Database and Experimental Tools  

SciTech Connect

Microbial functional genomics is faced with a burgeoning list of genes which are denoted as unknown or hypothetical for lack of any knowledge about their function. The majority of microbial genes encode enzymes. Enzymes are the catalysts of metabolism; catabolism, anabolism, stress responses, and many other cell functions. A major problem facing microbial functional genomics is proposed here to derive from the breadth of microbial metabolism, much of which remains undiscovered. The breadth of microbial metabolism has been surveyed by the PIs and represented according to reaction types on the University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD): http://umbbd.ahc.umn.edu/search/FuncGrps.html The database depicts metabolism of 49 chemical functional groups, representing most of current knowledge. Twice that number of chemical groups are proposed here to be metabolized by microbes. Thus, at least 50% of the unique biochemical reactions catalyzed by microbes remain undiscovered. This further suggests that many unknown and hypothetical genes encode functions yet undiscovered. This gap will be partly filled by the current proposal. The UM-BBD will be greatly expanded as a resource for microbial functional genomics. Computational methods will be developed to predict microbial metabolism which is not yet discovered. Moreover, a concentrated effort to discover new microbial metabolism will be conducted. The research will focus on metabolism of direct interest to DOE, dealing with the transformation of metals, metalloids, organometallics and toxic organics. This is precisely the type of metabolism which has been characterized most poorly to date. Moreover, these studies will directly impact functional genomic analysis of DOE-relevant genomes.

Lawrence P. Wackett; Lynda B.M. Ellis

2004-12-09

180

Gene discovery and transcript analyses in the corn smut pathogen Ustilago maydis: expressed sequence tag and genome sequence comparison  

PubMed Central

Background Ustilago maydis is the basidiomycete fungus responsible for common smut of corn and is a model organism for the study of fungal phytopathogenesis. To aid in the annotation of the genome sequence of this organism, several expressed sequence tag (EST) libraries were generated from a variety of U. maydis cell types. In addition to utility in the context of gene identification and structure annotation, the ESTs were analyzed to identify differentially abundant transcripts and to detect evidence of alternative splicing and anti-sense transcription. Results Four cDNA libraries were constructed using RNA isolated from U. maydis diploid teliospores (U. maydis strains 518 × 521) and haploid cells of strain 521 grown under nutrient rich, carbon starved, and nitrogen starved conditions. Using the genome sequence as a scaffold, the 15,901 ESTs were assembled into 6,101 contiguous expressed sequences (contigs); among these, 5,482 corresponded to predicted genes in the MUMDB (MIPS Ustilago maydis database), while 619 aligned to regions of the genome not yet designated as genes in MUMDB. A comparison of EST abundance identified numerous genes that may be regulated in a cell type or starvation-specific manner. The transcriptional response to nitrogen starvation was assessed using RT-qPCR. The results of this suggest that there may be cross-talk between the nitrogen and carbon signalling pathways in U. maydis. Bioinformatic analysis identified numerous examples of alternative splicing and anti-sense transcription. While intron retention was the predominant form of alternative splicing in U. maydis, other varieties were also evident (e.g. exon skipping). Selected instances of both alternative splicing and anti-sense transcription were independently confirmed using RT-PCR. Conclusion Through this work: 1) substantial sequence information has been provided for U. maydis genome annotation; 2) new genes were identified through the discovery of 619 contigs that had previously escaped annotation; 3) evidence is provided that suggests the regulation of nitrogen metabolism in U. maydis differs from that of other model fungi, and 4) Alternative splicing and anti-sense transcription were identified in U. maydis and, amid similar observations in other basidiomycetes, this suggests these phenomena may be widespread in this group of fungi. These advances emphasize the importance of EST analysis in genome annotation. PMID:17892571

Ho, Eric CH; Cahill, Matt J; Saville, Barry J

2007-01-01

181

Fish Suppressors of Cytokine Signaling (SOCS): Gene Discovery, Modulation of Expression and Function  

PubMed Central

The intracellular suppressors of cytokine signaling (SOCS) family members, including CISH and SOCS1 to 7 in mammals, are important regulators of cytokine signaling pathways. So far, the orthologues of all the eight mammalian SOCS members have been identified in fish, with several of them having multiple copies. Whilst fish CISH, SOCS3, and SOCS5 paralogues are possibly the result of the fish-specific whole genome duplication event, gene duplication or lineage-specific genome duplication may also contribute to some paralogues, as with the three trout SOCS2s and three zebrafish SOCS5s. Fish SOCS genes are broadly expressed and also show species-specific expression patterns. They can be upregulated by cytokines, such as IFN-?, TNF-?, IL-1?, IL-6, and IL-21, by immune stimulants such as LPS, poly I:C, and PMA, as well as by viral, bacterial, and parasitic infections in member- and species-dependent manners. Initial functional studies demonstrate conserved mechanisms of fish SOCS action via JAK/STAT pathways. PMID:22203897

Wang, Tiehui; Gorgoglione, Bartolomeo; Maehr, Tanja; Holland, Jason W.; Vecino, Jose L. Gonzalez; Wadsworth, Simon; Secombes, Christopher J.

2011-01-01

182

A large-scale gene discovery for the red palm weevil Rhynchophorus ferrugineus (Coleoptera: Curculionidae).  

PubMed

The red palm weevil (RPW; Rhynchophorus ferrugineus) is a devastating pest of palms, prevalent in the Middle East as well as many other regions of the world. Here, we report a large-scale de novo complementary DNA (cDNA) sequencing effort that acquired ?5 million reads and assembled them into 26?765 contigs from 12 libraries made from samples of different RPW developmental stages based on the Roche/454 GS FLX platform. We annotated these contigs based on the publically available known insect genes and the Tribolium castaneum genome assembly. We find that over 80% of coding sequences (CDS) from the RPW contigs have high-identity homologs to known proteins with complete CDS. Gene expression analysis shows that the pupa and larval stages have the highest and lowest expression levels, respectively. In addition, we also identified more than 60?000 single nucleotide polymorphisms and 1?200 simple sequence repeat markers. This study provides the first large-scale cDNA dataset for RPW, a much-needed resource for future molecular studies. PMID:23955844

Wang, Lei; Zhang, Xiao-Wei; Pan, Lin-Lin; Liu, Wan-Fei; Wang, Da-Peng; Zhang, Guang-Yu; Yin, Yu-Xin; Yin, An; Jia, Shan-Gang; Yu, Xiao-Guang; Sun, Gao-Yuan; Hu, Song-Nian; Al-Mssallem, Ibrahim S; Yu, Jun

2013-12-01

183

The long (and winding) road to gene discovery for canine hip dysplasia  

PubMed Central

Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1–2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a ‘breeding value’ that could improve the accuracy of predicting a dog’s hip conformation. PMID:19297220

Zhu, Lan; Zhang, Zhiwu; Friedenberg, Steven; Jung, Seung-Woo; Phavaphutanon, Janjira; Vernier-Singer, Margaret; Corey, Elizabeth; Mateescu, Raluca; Dykes, Nathan; Sandler, Jody; Acland, Gregory; Lust, George; Todhunter, Rory

2009-01-01

184

MixMir: microRNA motif discovery from gene expression data using mixed linear models.  

PubMed

microRNAs (miRNAs) are a class of ?22nt non-coding RNAs that potentially regulate over 60% of human protein-coding genes. miRNA activity is highly specific, differing between cell types, developmental stages and environmental conditions, so the identification of active miRNAs in a given sample is of great interest. Here we present a novel computational approach for analyzing both mRNA sequence and gene expression data, called MixMir. Our method corrects for 3' UTR background sequence similarity between transcripts, which is known to correlate with mRNA transcript abundance. We demonstrate that after accounting for kmer sequence similarities in 3' UTRs, a statistical linear model based on motif presence/absence can effectively discover active miRNAs in a sample. MixMir utilizes fast software implementations for solving mixed linear models, which are widely used in genome-wide association studies (GWASs). Essentially we use 3' UTR sequence similarity in place of population cryptic relatedness in the GWAS problem. Compared to similar methods such as miReduce, Sylamer and cWords, we found that MixMir performed better at discovering true miRNA motifs in three mouse Dicer-knockout experiments from different tissues, two of which were collected by our group. We confirmed these results on protein and mRNA expression data obtained from miRNA transfection experiments in human cell lines. MixMir can be freely downloaded from https://github.com/ldiao/MixMir. PMID:25081207

Diao, Liyang; Marcais, Antoine; Norton, Scott; Chen, Kevin C

2015-01-01

185

Discovery and characterization of the first genuine avian leptin gene in the rock dove (Columba livia).  

PubMed

Leptin, the key regulator of mammalian energy balance, has been at the center of a great controversy in avian biology for the last 15 years since initial reports of a putative leptin gene (LEP) in chickens. Here, we characterize a novel LEP in rock dove (Columba livia) with low similarity of the predicted protein sequence (30% identity, 47% similarity) to the human ortholog. Searching the Sequence-Read-Archive database revealed leptin transcripts, in the dove's liver, with 2 noncoding exons preceding 2 coding exons. This unusual 4-exon structure was validated by sequencing of a GC-rich product (76% GC, 721 bp) amplified from liver RNA by RT-PCR. Sequence alignment of the dove leptin with orthologous leptins indicated that it consists of a leader peptide (21 amino acids; aa) followed by the mature protein (160 aa), which has a putative structure typical of 4-helical-bundle cytokines except that it is 12 aa longer than human leptin. Extra residues (10 aa) were located within the loop between 2 5'-helices, interrupting the amino acid motif that is conserved in tetrapods and considered essential for activation of leptin receptor (LEPR) but not for receptor binding per se. Quantitative RT-PCR of 11 tissues showed highest (P < .05) expression of LEP in the dove's liver, whereas the dove LEPR peaked (P < .01) in the pituitary. Both genes were prominently expressed in the gonads and at lower levels in tissues involved in mammalian leptin signaling (adipose; hypothalamus). A bioassay based on activation of the chicken LEPR in vitro showed leptin activity in the dove's circulation, suggesting that dove LEP encodes an active protein, despite the interrupted loop motif. Providing tools to study energy-balance control at an evolutionary perspective, our original demonstration of leptin signaling in dove predicts a more ancient role of leptin in growth and reproduction in birds, rather than appetite control. PMID:24758303

Friedman-Einat, Miriam; Cogburn, Larry A; Yosefi, Sara; Hen, Gideon; Shinder, Dmitry; Shirak, Andrey; Seroussi, Eyal

2014-09-01

186

MixMir: microRNA motif discovery from gene expression data using mixed linear models  

PubMed Central

microRNAs (miRNAs) are a class of ?22nt non-coding RNAs that potentially regulate over 60% of human protein-coding genes. miRNA activity is highly specific, differing between cell types, developmental stages and environmental conditions, so the identification of active miRNAs in a given sample is of great interest. Here we present a novel computational approach for analyzing both mRNA sequence and gene expression data, called MixMir. Our method corrects for 3’ UTR background sequence similarity between transcripts, which is known to correlate with mRNA transcript abundance. We demonstrate that after accounting for kmer sequence similarities in 3’ UTRs, a statistical linear model based on motif presence/absence can effectively discover active miRNAs in a sample. MixMir utilizes fast software implementations for solving mixed linear models, which are widely used in genome-wide association studies (GWASs). Essentially we use 3’ UTR sequence similarity in place of population cryptic relatedness in the GWAS problem. Compared to similar methods such as miReduce, Sylamer and cWords, we found that MixMir performed better at discovering true miRNA motifs in three mouse Dicer-knockout experiments from different tissues, two of which were collected by our group. We confirmed these results on protein and mRNA expression data obtained from miRNA transfection experiments in human cell lines. MixMir can be freely downloaded from https://github.com/ldiao/MixMir. PMID:25081207

Diao, Liyang; Marcais, Antoine; Norton, Scott; Chen, Kevin C.

2014-01-01

187

Pattern discovery and cancer gene identification in integrated cancer genomic data  

PubMed Central

Large-scale integrated cancer genome characterization efforts including the cancer genome atlas and the cancer cell line encyclopedia have created unprecedented opportunities to study cancer biology in the context of knowing the entire catalog of genetic alterations. A clinically important challenge is to discover cancer subtypes and their molecular drivers in a comprehensive genetic context. Curtis et al. [Nature (2012) 486(7403):346–352] has recently shown that integrative clustering of copy number and gene expression in 2,000 breast tumors reveals novel subgroups beyond the classic expression subtypes that show distinct clinical outcomes. To extend the scope of integrative analysis for the inclusion of somatic mutation data by massively parallel sequencing, we propose a framework for joint modeling of discrete and continuous variables that arise from integrated genomic, epigenomic, and transcriptomic profiling. The core idea is motivated by the hypothesis that diverse molecular phenotypes can be predicted by a set of orthogonal latent variables that represent distinct molecular drivers, and thus can reveal tumor subgroups of biological and clinical importance. Using the cancer cell line encyclopedia dataset, we demonstrate our method can accurately group cell lines by their cell-of-origin for several cancer types, and precisely pinpoint their known and potential cancer driver genes. Our integrative analysis also demonstrates the power for revealing subgroups that are not lineage-dependent, but consist of different cancer types driven by a common genetic alteration. Application of the cancer genome atlas colorectal cancer data reveals distinct integrated tumor subtypes, suggesting different genetic pathways in colon cancer progression. PMID:23431203

Mo, Qianxing; Wang, Sijian; Seshan, Venkatraman E.; Olshen, Adam B.; Schultz, Nikolaus; Sander, Chris; Powers, R. Scott; Ladanyi, Marc; Shen, Ronglai

2013-01-01

188

Project Information Form Project Title Do California Highways Act as Barriers to Gene Flow for Ground-Dwelling  

E-print Network

Project Information Form Project Title Do California Highways Act as Barriers to Gene Flow to generalize results among systems. To begin to understand how Northern California highways affect native coyotes and non-invasive sources (hair and scat) on either side of each highway and use landscape genetic

California at Davis, University of

189

Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo.  

PubMed

Identifying new biomarkers and therapeutic targets for podocytopathies such as focal segmental glomerulosclerosis (FSGS) requires a detailed analysis of transcriptional changes in podocytes over the course of disease. Here we used translating ribosome affinity purification (TRAP) to isolate and profile podocyte-specific mRNA in two different models of FSGS. We expressed enhanced green fluorescent protein-tagged to ribosomal protein L10a in podocytes under the control of the collagen-1?1 promoter, enabling one-step podocyte-specific mRNA isolation over the course of disease. This TRAP protocol robustly enriched known podocyte-specific mRNAs. We crossed Col1?1-eGFP-L10a mice with the Actn4(-/-) and Actn4(+/K256E) models of FSGS and analyzed podocyte transcriptional profiles at 2, 6, and 44 weeks of age. Two upregulated podocyte genes in murine FSGS (CXCL1 and DMPK) were found to be upregulated at the protein level in biopsies from patients with FSGS, validating this approach. There was no dilution of podocyte-specific transcripts during disease. These are the first podocyte-specific RNA expression data sets during aging and in two models of FSGS. This approach identified new podocyte proteins that are upregulated in FSGS and defines novel biomarkers and therapeutic targets for human glomerular disease. PMID:24940801

Grgic, Ivica; Hofmeister, Andreas F; Genovese, Giulio; Bernhardy, Andrea J; Sun, Hua; Maarouf, Omar H; Bijol, Vanesa; Pollak, Martin R; Humphreys, Benjamin D

2014-12-01

190

Genetic and genomic approaches for the discovery of parasite genes involved in antimalarial drug resistance.  

PubMed

The biggest threat to the war on malaria is the continued evolution of drug resistance by the parasite. Resistance to almost all currently available antimalarials now exists in Plasmodium falciparum which causes the most suffering among all human malaria parasites. Monitoring of antimalarial efficacy and the development and subsequent spread of resistance has become an important part in the treatment and control of malaria. With recent reports of reduced efficacy of artemisinin, the current recommended treatment for uncomplicated malaria, there is urgent need for better methods to recognize and monitor drug resistance for effective treatment. Molecular markers have become a welcome addition to complement the more laborious and costly in vitro and in vivo methods that have traditionally been used to monitor drug resistance. However, there are currently no molecular markers for resistance to some antimalarials. This review highlights the role of the various genetic and genomic approaches that have been used in identifying the molecular markers that underlie drug resistance in P. falciparum. These approaches include; candidate genes, genetic linkage and genome-wide association studies. We discuss the requirements and limitations of each approach and use various examples to illustrate their contributions in identifying genomic regions of the parasite associated with antimalarial drug responses. PMID:23931581

Mwangi, Jonathan M; Ranford-Cartwright, Lisa C

2013-10-01

191

Discovery, taxonomic distribution, and phenotypic characterization of a gene required for 3-methylhopanoid production.  

PubMed

Hopanoids methylated at the C-3 position are a subset of bacterial triterpenoids that are readily preserved in modern and ancient sediments and in petroleum. The production of 3-methylhopanoids by extant aerobic methanotrophs and their common occurrence in modern and fossil methane seep communities, in conjunction with carbon isotope analysis, has led to their use as biomarker proxies for aerobic methanotrophy. In addition, these lipids are also produced by aerobic acetic acid bacteria and, lacking carbon isotope analysis, are more generally used as indicators for aerobiosis in ancient ecosystems. However, recent genetic studies have brought into question our current understanding of the taxonomic diversity of methylhopanoid-producing bacteria and have highlighted that a proper interpretation of methylhopanes in the rock record requires a deeper understanding of their cellular function. In this study, we identified and deleted a gene, hpnR, required for methylation of hopanoids at the C-3 position in the obligate methanotroph Methylococcus capsulatus strain Bath. Bioinformatics analysis revealed that the taxonomic distribution of HpnR extends beyond methanotrophic and acetic acid bacteria. Phenotypic analysis of the M. capsulatus hpnR deletion mutant demonstrated a potential physiological role for 3-methylhopanoids; they appear to be required for the maintenance of intracytoplasmic membranes and cell survival in late stationary phase. Therefore, 3-methylhopanoids may prove more useful as proxies for specific environmental conditions encountered during stationary phase rather than a particular bacterial group. PMID:22826256

Welander, Paula V; Summons, Roger E

2012-08-01

192

Discovery, taxonomic distribution, and phenotypic characterization of a gene required for 3-methylhopanoid production  

PubMed Central

Hopanoids methylated at the C-3 position are a subset of bacterial triterpenoids that are readily preserved in modern and ancient sediments and in petroleum. The production of 3-methylhopanoids by extant aerobic methanotrophs and their common occurrence in modern and fossil methane seep communities, in conjunction with carbon isotope analysis, has led to their use as biomarker proxies for aerobic methanotrophy. In addition, these lipids are also produced by aerobic acetic acid bacteria and, lacking carbon isotope analysis, are more generally used as indicators for aerobiosis in ancient ecosystems. However, recent genetic studies have brought into question our current understanding of the taxonomic diversity of methylhopanoid-producing bacteria and have highlighted that a proper interpretation of methylhopanes in the rock record requires a deeper understanding of their cellular function. In this study, we identified and deleted a gene, hpnR, required for methylation of hopanoids at the C-3 position in the obligate methanotroph Methylococcus capsulatus strain Bath. Bioinformatics analysis revealed that the taxonomic distribution of HpnR extends beyond methanotrophic and acetic acid bacteria. Phenotypic analysis of the M. capsulatus hpnR deletion mutant demonstrated a potential physiological role for 3-methylhopanoids; they appear to be required for the maintenance of intracytoplasmic membranes and cell survival in late stationary phase. Therefore, 3-methylhopanoids may prove more useful as proxies for specific environmental conditions encountered during stationary phase rather than a particular bacterial group. PMID:22826256

Welander, Paula V.; Summons, Roger E.

2012-01-01

193

Discovery of molecular associations among aging, stem cells, and cancer based on gene expression profiling  

PubMed Central

The emergence of a huge volume of “omics” data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experimental approach. I reviewed several reports that used a bioinformatics approach to analyze the associations among aging, stem cells, and cancer by microarray gene expression profiling. The high expression of aging- or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging, stem cells, and cancer. These mechanisms are involved in cell cycle regulation, metabolic process, DNA damage response, apoptosis, p53 signaling pathway, immune/inflammatory response, and other processes, suggesting that cancer is a developmental and evolutional disease that is strongly related to aging. Moreover, these mechanisms demonstrate that the initiation, proliferation, and metastasis of cancer are associated with the deregulation of stem cells. These findings provide insights into the biology of cancer. Certainly, the findings that are obtained by the informatics approach should be justified by experimental validation. This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study. PMID:23298462

Wang, Xiaosheng

2013-01-01

194

Integration of Cot Analysis, DNA Cloning, and High-Throughput Sequencing Facilitates Genome Characterization and Gene Discovery  

PubMed Central

Cot-based sequence discovery represents a powerful means by which both low-copy and repetitive sequences can be selectively and efficiently fractionated, cloned, and characterized. Based upon the results of a Cot analysis, hydroxyapatite chromatography was used to fractionate sorghum (Sorghum bicolor) genomic DNA into highly repetitive (HR), moderately repetitive (MR), and single/low-copy (SL) sequence components that were consequently cloned to produce HRCot, MRCot, and SLCot genomic libraries. Filter hybridization (blotting) and sequence analysis both show that the HRCot library is enriched in sequences traditionally found in high-copy number (e.g., retroelements, rDNA, centromeric repeats), the SLCot library is enriched in low-copy sequences (e.g., genes and “nonrepetitive ESTs”), and the MRCot library contains sequences of moderate redundancy. The Cot analysis suggests that the sorghum genome is approximately 700 Mb (in agreement with previous estimates) and that HR, MR, and SL components comprise 15%, 41%, and 24% of sorghum DNA, respectively. Unlike previously described techniques to sequence the low-copy components of genomes, sequencing of Cot components is independent of expression and methylation patterns that vary widely among DNA elements, developmental stages, and taxa. High-throughput sequencing of Cot clones may be a means of “capturing” the sequence complexity of eukaryotic genomes at unprecedented efficiency. [Online supplementary material is available at www.genome.org. The sequence data described in this paper have been submitted to the GenBank under accession nos. AZ921847-AZ923007. Reagents, samples, and unpublished information freely provided by H. Ma and J. Messing.] PMID:11997346

Peterson, Daniel G.; Schulze, Stefan R.; Sciara, Erica B.; Lee, Scott A.; Bowers, John E.; Nagel, Alexander; Jiang, Ning; Tibbitts, Deanne C.; Wessler, Susan R.; Paterson, Andrew H.

2002-01-01

195

NCI DTP Discovery Services  

Cancer.gov

What's New Home Discovery Development Pathways Grants/Contracts Books/Publications Site Search Data Search What's New MicroXeno Project data now available NCI-60 characterization NCI Experimental Therapeutics Program (NExT)

196

A critical assessment of Agrobacterium tumefaciens-mediated transformation as a tool for pathogenicity gene discovery in the phytopathogenic fungus Leptosphaeria maculans.  

PubMed

We evaluated the usefulness and robustness of Agrobacterium tumefaciens-mediated transformation (ATMT) as a high-throughput transformation tool for pathogenicity gene discovery in the filamentous phytopathogen Leptosphaeria maculans. Thermal asymmetric interlaced polymerase chain reaction allowed us to amplify the left border (LB) flanking sequence in 135 of 400 transformants analysed, and indicated a high level of preservation of the T-DNA LB. In addition, T-DNA preferentially integrated as a single copy in gene-rich regions of the fungal genome, with a probable bias towards intergenic and/or regulatory regions. A total of 53 transformants out of 1388 (3.8%) showed reproducible pathogenicity defects when inoculated on cotyledons of Brassica napus, with diverse altered phenotypes. Co-segregation of the altered phenotype with the T-DNA integration was observed for 6 of 12 transformants crossed. If extrapolated to the whole collection, this indicates that 1.9% of the collection actually corresponds to tagged pathogenicity mutants. The preferential insertion into gene-rich regions along with the high ratio of tagged mutants renders ATMT a tool of choice for large-scale gene discovery in L. maculans. PMID:16979359

Blaise, Françoise; Rémy, Estelle; Meyer, Michel; Zhou, Ligang; Narcy, Jean-Paul; Roux, Jacqueline; Balesdent, Marie-Hélène; Rouxel, Thierry

2007-02-01

197

Interestingness measures and strategies for mining multi-ontology multi-level association rules from gene ontology annotations for the discovery of new GO relationships.  

PubMed

The Gene Ontology (GO), a set of three sub-ontologies, is one of the most popular bio-ontologies used for describing gene product characteristics. GO annotation data containing terms from multiple sub-ontologies and at different levels in the ontologies is an important source of implicit relationships between terms from the three sub-ontologies. Data mining techniques such as association rule mining that are tailored to mine from multiple ontologies at multiple levels of abstraction are required for effective knowledge discovery from GO annotation data. We present a data mining approach, Multi-ontology data mining at All Levels (MOAL) that uses the structure and relationships of the GO to mine multi-ontology multi-level association rules. We introduce two interestingness measures: Multi-ontology Support (MOSupport) and Multi-ontology Confidence (MOConfidence) customized to evaluate multi-ontology multi-level association rules. We also describe a variety of post-processing strategies for pruning uninteresting rules. We use publicly available GO annotation data to demonstrate our methods with respect to two applications (1) the discovery of co-annotation suggestions and (2) the discovery of new cross-ontology relationships. PMID:23850840

Manda, Prashanti; McCarthy, Fiona; Bridges, Susan M

2013-10-01

198

FAF-Drugs2: Free ADME\\/tox filtering tool to assist drug discovery and chemical biology projects  

Microsoft Academic Search

BACKGROUND: Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting\\/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying

David Lagorce; Olivier Sperandio; Hervé Galons; Maria A. Miteva; Bruno O. Villoutreix

2008-01-01

199

Gene disruptions using P transposable elements: an integral component of the Drosophila genome project.  

PubMed Central

Biologists require genetic as well as molecular tools to decipher genomic information and ultimately to understand gene function. The Berkeley Drosophila Genome Project is addressing these needs with a massive gene disruption project that uses individual, genetically engineered P transposable elements to target open reading frames throughout the Drosophila genome. DNA flanking the insertions is sequenced, thereby placing an extensive series of genetic markers on the physical genomic map and associating insertions with specific open reading frames and genes. Insertions from the collection now lie within or near most Drosophila genes, greatly reducing the time required to identify new mutations and analyze gene functions. Information revealed from these studies about P element site specificity is being used to target the remaining open reading frames. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7479892

Spradling, A C; Stern, D M; Kiss, I; Roote, J; Laverty, T; Rubin, G M

1995-01-01

200

The Genetics of Obsessive-Compulsive Disorder and Tourette Syndrome: An Epidemiological and Pathway-Based Approach for Gene Discovery  

ERIC Educational Resources Information Center

Objective: To provide a contemporary perspective on genetic discovery methods applied to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). Method: A review of research trends in genetics research in OCD and TS is conducted, with emphasis on novel approaches. Results: Genome-wide association studies (GWAS) are now in progress in OCD…

Grados, Marco A.

2010-01-01

201

Guided Discoveries.  

ERIC Educational Resources Information Center

Presented are four mathematical discoveries made by students on an arithmetical function using the Fibonacci sequence. Discussed is the nature of the role of the teacher in directing the students' discovery activities. (KR)

Ehrlich, Amos

1991-01-01

202

Natural product proteomining, a quantitative proteomics platform, allows rapid discovery of biosynthetic gene clusters for different classes of natural products.  

PubMed

Information on gene clusters for natural product biosynthesis is accumulating rapidly because of the current boom of available genome sequencing data. However, linking a natural product to a specific gene cluster remains challenging. Here, we present a widely applicable strategy for the identification of gene clusters for specific natural products, which we name natural product proteomining. The method is based on using fluctuating growth conditions that ensure differential biosynthesis of the bioactivity of interest. Subsequent combination of metabolomics and quantitative proteomics establishes correlations between abundance of natural products and concomitant changes in the protein pool, which allows identification of the relevant biosynthetic gene cluster. We used this approach to elucidate gene clusters for different natural products in Bacillus and Streptomyces, including a novel juglomycin-type antibiotic. Natural product proteomining does not require prior knowledge of the gene cluster or secondary metabolite and therefore represents a general strategy for identification of all types of gene clusters. PMID:24816229

Gubbens, Jacob; Zhu, Hua; Girard, Geneviève; Song, Lijiang; Florea, Bogdan I; Aston, Philip; Ichinose, Koji; Filippov, Dmitri V; Choi, Young H; Overkleeft, Herman S; Challis, Gregory L; van Wezel, Gilles P

2014-06-19

203

Development of a system for discovery of genetic interactions for essential genes in Escherichia coli K-12.  

PubMed

Genetic interaction networks are especially useful for functional assignment of genes and gaining new insights into the systems-level organization of the cell. While studying interactions of nonessential genes can be relatively straight-forward via use of deletion mutants, different approaches must be used to reveal interactions of essential genes due to their indispensability. One method shown to be useful for revealing interactions of essential genes requires tagging the query protein. However, this approach can be complicated by mutational effects of potential hypomorphic alleles. Here, we describe a pilot study for a new scheme of systematically studying the interactions of essential genes. Our method uses a low-copy, F-based, complementing plasmid, pFE604T, from which the essential gene is conditionally expressed. The essential gene is expressed at lower levels, producing a moderate growth defect in a query host. Secondary mutations are introduced into the query host by conjugation and the resultant exconjugants are scored for growth by imaging them over time. We report results from studying five essential query genes: dnaN, ftsW, trmD, yrfF and yjgP, showing (on average) interactions with nearly 80 nonessential genes. This system should prove useful for genome-wide analyses of other essential genes in E. coli K-12. PMID:24463526

Yong, Han Tek; Yamamoto, Natsuko; Takeuchi, Rikiya; Hsieh, Yi-Ju; Conrad, Tom M; Datsenko, Kirill A; Nakayashiki, Toru; Wanner, Barry L; Mori, Hirotada

2013-01-01

204

TOXICOGENOMICS DRUG DISCOVERY AND THE PATHOLOGIST  

EPA Science Inventory

Toxicogenomics, drug discovery, and pathologist. The field of toxicogenomics, which currently focuses on the application of large-scale differential gene expression (DGE) data to toxicology, is starting to influence drug discovery and development in the pharmaceutical indu...

205

Simultaneous structure discovery and parameter estimation in gene networks using a multi-objective GP-PSO hybrid approach.  

PubMed

This paper presents a hybrid algorithm based on Genetic Programming (GP) and Particle Swarm Optimisation (PSO) for the automated recovery of gene network structure. It uses gene expression time series data as well as phenotypic data pertaining to plant flowering time as its input data. The algorithm then attempts to discover simple structures to approximate the plant gene regulatory networks that produce model gene expressions and flowering times that closely resemble the input data. To show the efficacy of the proposed approach, simulation results applied to flowering time control in Arabidopsis thaliana are demonstrated and discussed. PMID:19525199

Cai, Xinye; Koduru, Praveen; Das, Sanjoy; Welch, Stephen M

2009-01-01

206

Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing  

PubMed Central

Half of prostate cancers harbor gene fusions between TMPRSS2 and members of the ETS transcription factor family. To date, little is known about the presence of non-ETS fusion events in prostate cancer. We used next-generation transcriptome sequencing (RNA-seq) in order to explore the whole transcriptome of 25 human prostate cancer samples for the presence of chimeric fusion transcripts. We generated more than 1 billion sequence reads and used a novel computational approach (FusionSeq) in order to identify novel gene fusion candidates with high confidence. In total, we discovered and characterized seven new cancer-specific gene fusions, two involving the ETS genes ETV1 and ERG, and four involving non-ETS genes such as CDKN1A (p21), CD9, and IKBKB (IKK-beta), genes known to exhibit key biological roles in cellular homeostasis or assumed to be critical in tumorigenesis of other tumor entities, as well as the oncogene PIGU and the tumor suppressor gene RSRC2. The novel gene fusions are found to be of low frequency, but, interestingly, the non-ETS fusions were all present in prostate cancer harboring the TMPRSS2–ERG gene fusion. Future work will focus on determining if the ETS rearrangements in prostate cancer are associated or directly predispose to a rearrangement-prone phenotype. PMID:21036922

Pflueger, Dorothee; Terry, Stephane; Sboner, Andrea; Habegger, Lukas; Esgueva, Raquel; Lin, Pei-Chun; Svensson, Maria A.; Kitabayashi, Naoki; Moss, Benjamin J.; MacDonald, Theresa Y.; Cao, Xuhong; Barrette, Terrence; Tewari, Ashutosh K.; Chee, Mark S.; Chinnaiyan, Arul M.; Rickman, David S.; Demichelis, Francesca; Gerstein, Mark B.; Rubin, Mark A.

2011-01-01

207

Manipulating gene expression in projection-specific neuronal populations using combinatorial viral approaches  

PubMed Central

The mammalian brain contains tremendous structural and genetic complexity that is vital for its function. The elucidation of gene expression profiles in the brain, coupled with the development of large-scale connectivity maps and emerging viral vector-based approaches for target-selective gene manipulation, now allow for detailed dissection of gene-circuit interfaces. This protocol details how to perform combinatorial viral injections to manipulate gene expression in subsets of neurons interconnecting two brain regions. This method utilizes stereotaxic injection of a retrograde transducing CAV2-Cre virus into one brain region, combined with injection of a locally transducing Cre-dependent AAV virus into another brain region. This technique is widely applicable to the genetic dissection of neural circuitry, as it enables selective expression of candidate genes, dominant-negatives, fluorescent reporters, or genetic tools within heterogeneous populations of neurons based upon their projection targets.

Gore, Bryan B.; Soden, Marta E.; Zweifel, Larry S.

2013-01-01

208

The discovery of the two types of small subunit ribosomal RNA gene in Eimeria mitis contests the existence of E. mivati as an independent species.  

PubMed

Although the validity of the coccidian species, Eimeria mivati, has been questioned by many researchers for a long time there has not been any molecular analysis that would help resolve this issue. Here we report on the discovery of the two types of small ribosomal subunit (18S) gene within the Eimeria mitis genome that correspond to the known 18S sequences of E. mitis and E. mivati, and this is in conflict with the existence of E. mivati as an independent species. We have carried out five single oocyst isolations to obtain five single-oocyst-derived strains of E. mitis and these were analyzed by the sequencing of 18S and mitochondrial cytochrome c oxidase subunit I genes. The two types of 18S gene were found to be present in each strain in roughly equal ratios. This indicates that if the strains carrying only one or the other 18S type exist, they will likely cross-breed and still represent a single species. However, the more probable explanation is that all strains of E. mitis contain two types of 18S gene and that the occasional detection of only one or the other type by sequencing might be caused by insufficient sampling. This is also the first report of the two types of 18S gene in Eimeria, which has already been described in some other apicomplexan species, most notably Plasmodium. We also found that these two types of ribosomal RNA differ significantly in their secondary structure. The biological significance of the two 18S gene variants in E. mitis is not known, however, we hypothesize that these variants might be used in different stages of the parasite's life-cycle as it is in other apicomplexan species investigated so far. PMID:21767912

Vrba, Vladimir; Poplstein, Martin; Pakandl, Michal

2011-12-29

209

Coupled Transcriptome and Proteome Analysis of Human Lymphotropic Tumor Viruses: Insights on the Detection and Discovery of Viral Genes  

SciTech Connect

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are related human tumor viruses that cause primary effusion lymphomas (PEL) and Burkitt's lymphomas (BL), respectively. Viral genes expressed in naturally-infected cancer cells contribute to disease pathogenesis; knowing which viral genes are expressed is critical in understanding how these viruses cause cancer. To evaluate the expression of viral genes, we used high-resolution separation and mass spectrometry coupled with custom tiling arrays to align the viral proteomes and transcriptomes of three PEL and two BL cell lines under latent and lytic culture conditions. Results The majority of viral genes were efficiently detected at the transcript and/or protein level on manipulating the viral life cycle. Overall the correlation of expressed viral proteins and transcripts was highly complementary in both validating and providing orthogonal data with latent/lytic viral gene expression. Our approach also identified novel viral genes in both KSHV and EBV, and extends viral genome annotation. Several previously uncharacterized genes were validated at both transcript and protein levels. Conclusions This systems biology approach coupling proteome and transcriptome measurements provides a comprehensive view of viral gene expression that could not have been attained using each methodology independently. Detection of viral proteins in combination with viral transcripts is a potentially powerful method for establishing virus-disease relationships.

Dresang, Lindsay R.; Teuton, Jeremy R.; Feng, Huichen; Jacobs, Jon M.; Camp, David G.; Purvine, Samuel O.; Gritsenko, Marina A.; Li, Zhihua; Smith, Richard D.; Sugden, Bill; Moore, Patrick S.; Chang, Yuan

2011-12-20

210

The discovery that mutations in single genes can modulate aging was not only fascinating but it provided  

E-print Network

aging rates [1-2]. According to the GenAge database [3], at the time of writing, genetic manipulations in 68 genes have been shown to affect lifespan in mice. Among mouse genes in which mutations extend-13]. Although conducted in different labs and strains, bi-maternal mice had a similar increase in average

de Magalhães, João Pedro

211

Discovery Informatics: AI Opportunities in Scientific Discovery  

E-print Network

Discovery Informatics: AI Opportunities in Scientific Discovery Yolanda Gil Information Sciences and replicate processes of scientific discovery. This article discusses Discovery Informatics as an emerging and information systems to understand, automate, improve, and innovate processes of scientific discovery

Gil, Yolanda

212

Discovery of genes related to witches broom disease in Paulownia tomentosa × Paulownia fortunei by a De Novo assembled transcriptome.  

PubMed

In spite of its economic importance, very little molecular genetics and genomic research has been targeted at the family Paulownia spp. The little genetic information on this plant is a big obstacle to studying the mechanisms of its ability to resist Paulownia Witches' Broom (PaWB) disease. Analysis of the Paulownia transcriptome and its expression profile data are essential to extending the genetic resources on this species, thus will greatly improves our studies on Paulownia. In the current study, we performed the de novo assembly of a transcriptome on P. tomentosa × P. fortunei using the short-read sequencing technology (Illumina). 203,664 unigenes with a mean length of 1,328 bp was obtained. Of these unigenes, 32,976 (30% of all unigenes) containing complete structures were chosen. Eukaryotic clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed of these unigenes. Genes related to PaWB disease resistance were analyzed in detail. To our knowledge, this is the first study to elucidate the genetic makeup of Paulownia. This transcriptome provides a quick way to understanding Paulownia, increases the number of gene sequences available for further functional genomics studies and provides clues to the identification of potential PaWB disease resistance genes. This study has provided a comprehensive insight into gene expression profiles at different states, which facilitates the study of each gene's roles in the developmental process and in PaWB disease resistance. PMID:24278262

Liu, Rongning; Dong, Yanpeng; Fan, Guoqiang; Zhao, Zhenli; Deng, Minjie; Cao, Xibing; Niu, Suyan

2013-01-01

213

NK cell-based approach for screening novel functional immune genes  

Microsoft Academic Search

The human genome project provides extensive opportunities for the discovery of novel functional immune genes. In order to find innate immune genes that might regulate the function of NK cells from a cDNA library, we used an NK cell line, NK-92, as a platform to screen candidate genes. After comparing with other gene transfer methods, electroporation was selected as the

Longyan Wu; Cai Zhang; Zhigang Tian; Jian Zhang

2011-01-01

214

Discovery of genes related to insecticide resistance in Bactrocera dorsalis by functional genomic analysis of a de novo assembled transcriptome.  

PubMed

Insecticide resistance has recently become a critical concern for control of many insect pest species. Genome sequencing and global quantization of gene expression through analysis of the transcriptome can provide useful information relevant to this challenging problem. The oriental fruit fly, Bactrocera dorsalis, is one of the world's most destructive agricultural pests, and recently it has been used as a target for studies of genetic mechanisms related to insecticide resistance. However, prior to this study, the molecular data available for this species was largely limited to genes identified through homology. To provide a broader pool of gene sequences of potential interest with regard to insecticide resistance, this study uses whole transcriptome analysis developed through de novo assembly of short reads generated by next-generation sequencing (NGS). The transcriptome of B. dorsalis was initially constructed using Illumina's Solexa sequencing technology. Qualified reads were assembled into contigs and potential splicing variants (isotigs). A total of 29,067 isotigs have putative homologues in the non-redundant (nr) protein database from NCBI, and 11,073 of these correspond to distinct D. melanogaster proteins in the RefSeq database. Approximately 5,546 isotigs contain coding sequences that are at least 80% complete and appear to represent B. dorsalis genes. We observed a strong correlation between the completeness of the assembled sequences and the expression intensity of the transcripts. The assembled sequences were also used to identify large numbers of genes potentially belonging to families related to insecticide resistance. A total of 90 P450-, 42 GST-and 37 COE-related genes, representing three major enzyme families involved in insecticide metabolism and resistance, were identified. In addition, 36 isotigs were discovered to contain target site sequences related to four classes of resistance genes. Identified sequence motifs were also analyzed to characterize putative polypeptide translational products and associate them with specific genes and protein functions. PMID:22879883

Hsu, Ju-Chun; Chien, Ting-Ying; Hu, Chia-Cheng; Chen, Mei-Ju May; Wu, Wen-Jer; Feng, Hai-Tung; Haymer, David S; Chen, Chien-Yu

2012-01-01

215

De Novo Assembly, Gene Annotation, and Marker Discovery in Stored-Product Pest Liposcelis entomophila (Enderlein) Using Transcriptome Sequences  

PubMed Central

Background As a major stored-product pest insect, Liposcelis entomophila has developed high levels of resistance to various insecticides in grain storage systems. However, the molecular mechanisms underlying resistance and environmental stress have not been characterized. To date, there is a lack of genomic information for this species. Therefore, studies aimed at profiling the L. entomophila transcriptome would provide a better understanding of the biological functions at the molecular levels. Methodology/Principal Findings We applied Illumina sequencing technology to sequence the transcriptome of L. entomophila. A total of 54,406,328 clean reads were obtained and that de novo assembled into 54,220 unigenes, with an average length of 571 bp. Through a similarity search, 33,404 (61.61%) unigenes were matched to known proteins in the NCBI non-redundant (Nr) protein database. These unigenes were further functionally annotated with gene ontology (GO), cluster of orthologous groups of proteins (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A large number of genes potentially involved in insecticide resistance were manually curated, including 68 putative cytochrome P450 genes, 37 putative glutathione S-transferase (GST) genes, 19 putative carboxyl/cholinesterase (CCE) genes, and other 126 transcripts to contain target site sequences or encoding detoxification genes representing eight types of resistance enzymes. Furthermore, to gain insight into the molecular basis of the L. entomophila toward thermal stresses, 25 heat shock protein (Hsp) genes were identified. In addition, 1,100 SSRs and 57,757 SNPs were detected and 231 pairs of SSR primes were designed for investigating the genetic diversity in future. Conclusions/Significance We developed a comprehensive transcriptomic database for L. entomophila. These sequences and putative molecular markers would further promote our understanding of the molecular mechanisms underlying insecticide resistance or environmental stress, and will facilitate studies on population genetics for psocids, as well as providing useful information for functional genomic research in the future. PMID:24244605

Wei, Dan-Dan; Chen, Er-Hu; Ding, Tian-Bo; Chen, Shi-Chun; Dou, Wei; Wang, Jin-Jun

2013-01-01

216

SNP discovery, validation, haplotype structure and linkage disequilibrium in full-length herbage nutritive quality genes of perennial ryegrass (Lolium perenne L.).  

PubMed

Development of accurate high-throughput molecular marker systems such as SNPs permits evaluation and selection of favourable gene variants to accelerate elite varietal production. SNP discovery in perennial ryegrass has been based on PCR amplification and sequencing of multiple amplicons designed to scan all components of the transcriptional unit. Full-length genes (with complete intron-exon structure and promoter information) corresponding to well-defined biochemical functions such as lignin biosynthesis and oligosaccharide metabolism are ideal for complete SNP haplotype determination. Multiple SNPs at regular intervals across the transcriptional unit were detected within and between the heterozygous parents and validated in the progeny of the F (1)(NA(6) x AU(6)) genetic mapping family. Haplotype structures in the parental genotypes were defined and haplotypic abundance, structure and variation were assessed in diverse germplasm sources. Decay of LD to r (2) values of c. 0.2 typically occurs over 500-3,000 bp, comparable with gene length and with little apparent variation between diverse, ecotypic and varietal population sub-groups. Similar patterns were revealed as limited blocks of intragenic LD. The results are compatible with the reproductive biology of perennial ryegrass and the effects of large ancestral population size. This analysis provides crucial information to validate strategies for correlation of haplotypic diversity and phenotypic variation through association mapping. PMID:17647019

Ponting, Rebecca C; Drayton, Michelle C; Cogan, Noel O I; Dobrowolski, Mark P; Spangenberg, Germán C; Smith, Kevin F; Forster, John W

2007-11-01

217

Whole genome shotgun sequencing of Brassica oleracea and its application to gene discovery and annotation in Arabidopsis.  

PubMed

Through comparative studies of the model organism Arabidopsis thaliana and its close relative Brassica oleracea, we have identified conserved regions that represent potentially functional sequences overlooked by previous Arabidopsis genome annotation methods. A total of 454,274 whole genome shotgun sequences covering 283 Mb (0.44 x) of the estimated 650 Mb Brassica genome were searched against the Arabidopsis genome, and conserved Arabidopsis genome sequences (CAGSs) were identified. Of these 229,735 conserved regions, 167,357 fell within or intersected existing gene models, while 60,378 were located in previously unannotated regions. After removal of sequences matching known proteins, CAGSs that were close to one another were chained together as potentially comprising portions of the same functional unit. This resulted in 27,347 chains of which 15,686 were sufficiently distant from existing gene annotations to be considered a novel conserved unit. Of 192 conserved regions examined, 58 were found to be expressed in our cDNA populations. Rapid amplification of cDNA ends (RACE) was used to obtain potentially full-length transcripts from these 58 regions. The resulting sequences led to the creation of 21 gene models at 17 new Arabidopsis loci and the addition of splice variants or updates to another 19 gene structures. In addition, CAGSs overlapping already annotated genes in Arabidopsis can provide guidance for manual improvement of existing gene models. Published genome-wide expression data based on whole genome tiling arrays and massively parallel signature sequencing were overlaid on the Brassica-Arabidopsis conserved sequences, and 1399 regions of intersection were identified. Collectively our results and these data sets suggest that several thousand new Arabidopsis genes remain to be identified and annotated. PMID:15805490

Ayele, Mulu; Haas, Brian J; Kumar, Nikhil; Wu, Hank; Xiao, Yongli; Van Aken, Susan; Utterback, Teresa R; Wortman, Jennifer R; White, Owen R; Town, Christopher D

2005-04-01

218

Whole genome shotgun sequencing of Brassica oleracea and its application to gene discovery and annotation in Arabidopsis  

PubMed Central

Through comparative studies of the model organism Arabidopsis thaliana and its close relative Brassica oleracea, we have identified conserved regions that represent potentially functional sequences overlooked by previous Arabidopsis genome annotation methods. A total of 454,274 whole genome shotgun sequences covering 283 Mb (0.44×) of the estimated 650 Mb Brassica genome were searched against the Arabidopsis genome, and conserved Arabidopsis genome sequences (CAGSs) were identified. Of these 229,735 conserved regions, 167,357 fell within or intersected existing gene models, while 60,378 were located in previously unannotated regions. After removal of sequences matching known proteins, CAGSs that were close to one another were chained together as potentially comprising portions of the same functional unit. This resulted in 27,347 chains of which 15,686 were sufficiently distant from existing gene annotations to be considered a novel conserved unit. Of 192 conserved regions examined, 58 were found to be expressed in our cDNA populations. Rapid amplification of cDNA ends (RACE) was used to obtain potentially full-length transcripts from these 58 regions. The resulting sequences led to the creation of 21 gene models at 17 new Arabidopsis loci and the addition of splice variants or updates to another 19 gene structures. In addition, CAGSs overlapping already annotated genes in Arabidopsis can provide guidance for manual improvement of existing gene models. Published genome-wide expression data based on whole genome tiling arrays and massively parallel signature sequencing were overlaid on the Brassica–Arabidopsis conserved sequences, and 1399 regions of intersection were identified. Collectively our results and these data sets suggest that several thousand new Arabidopsis genes remain to be identified and annotated. PMID:15805490

Ayele, Mulu; Haas, Brian J.; Kumar, Nikhil; Wu, Hank; Xiao, Yongli; Van Aken, Susan; Utterback, Teresa R.; Wortman, Jennifer R.; White, Owen R.; Town, Christopher D.

2005-01-01

219

Transcriptome-based discovery of pathways and genes related to resistance against Fusarium head blight in wheat landrace Wangshuibai  

PubMed Central

Background Fusarium head blight (FHB), caused mainly by Fusarium graminearum (Fg) Schwabe (teleomorph: Gibberellazeae Schwble), brings serious damage to wheat production. Chinese wheat landrace Wangshuibai is one of the most important resistance sources in the world. The knowledge of mechanism underlying its resistance to FHB is still limited. Results To get an overview of transcriptome characteristics of Wangshuibai during infection by Fg, a high-throughput RNA sequencing based on next generation sequencing (NGS) technology (Illumina) were performed. Totally, 165,499 unigenes were generated and assigned to known protein databases including NCBI non-redundant protein database (nr) (82,721, 50.0%), Gene Ontology (GO) (38,184, 23.1%), Swiss-Prot (50,702, 30.6%), Clusters of orthologous groups (COG) (51,566, 31.2%) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) (30,657, 18.5%), as determined by Blastx search. With another NGS based platform, a digital gene expression (DGE) system, gene expression in Wangshuibai and its FHB susceptible mutant NAUH117 was profiled and compared at two infection stages by inoculation of Fg at 24 and 48 hour, with the aim of identifying genes involved in FHB resistance. Conclusion Pathogen-related proteins such as PR5, PR14 and ABC transporter and JA signaling pathway were crucial for FHB resistance, especially that mediated by Fhb1. ET pathway and ROS/NO pathway were not activated in Wangshuibai and may be not pivotal in defense to FHB. Consistent with the fact that in NAUH117 there presented a chromosome fragment deletion, which led to its increased FHB susceptibility, in Wangshuibai, twenty out of eighty-nine genes showed changed expression patterns upon the infection of Fg. The up-regulation of eight of them was confirmed by qRT-PCR, revealing they may be candidate genes for Fhb1 and need further functional analysis to confirm their roles in FHB resistance. PMID:23514540

2013-01-01

220

A Practical Introduction to Electronic Discovery aka e-data discovery; digital discovery; computer discovery  

E-print Network

A Practical Introduction to Electronic Discovery aka e-data discovery; digital discovery; computer discovery How to discover what you cannot see Hazards of electronic discovery................................................................................................................................6 Should e-discovery be permitted

Shamos, Michael I.

221

Discovery and characterization of miRNA genes in atlantic salmon (Salmo salar) by use of a deep sequencing approach  

PubMed Central

Background MicroRNAs (miRNAs) are an abundant class of endogenous small RNA molecules that downregulate gene expression at the posttranscriptional level. They play important roles in multiple biological processes by regulating genes that control developmental timing, growth, stem cell division and apoptosis by binding to the mRNA of target genes. Despite the position Atlantic salmon (Salmo salar) has as an economically important domesticated animal, there has been little research on miRNAs in this species. Knowledge about miRNAs and their target genes may be used to control health and to improve performance of economically important traits. However, before their biological function can be unravelled they must be identified and annotated. The aims of this study were to identify and characterize miRNA genes in Atlantic salmon by deep sequencing analysis of small RNA libraries from nine different tissues. Results A total of 180 distinct mature miRNAs belonging to 106 families of evolutionary conserved miRNAs, and 13 distinct novel mature miRNAs were discovered and characterized. The mature miRNAs corresponded to 521 putative precursor sequences located at unique genome locations. About 40% of these precursors were part of gene clusters, and the majority of the Salmo salar gene clusters discovered were conserved across species. Comparison of expression levels in samples from different tissues applying DESeq indicated that there were tissue specific expression differences in three conserved and one novel miRNA. Ssa-miR 736 was detected in heart tissue only, while two other clustered miRNAs (ssa-miR 212 and132) seems to be at a higher expression level in brain tissue. These observations correlate well with their expected functions as regulators of signal pathways in cardiac and neuronal cells, respectively. Ssa-miR 8163 is one of the novel miRNAs discovered and its function remains unknown. However, differential expression analysis using DESeq suggests that this miRNA is enriched in liver tissue and the precursor was mapped to intron 7 of the transferrin gene. Conclusions The identification and annotation of evolutionary conserved and novel Salmo salar miRNAs as well as the characterization of miRNA gene clusters provide biological knowledge that will greatly facilitate further functional studies on miRNAs in this species. PMID:23865519

2013-01-01

222

Discovery of Novel Leaf Rust Responsive microRNAs in Wheat and Prediction of Their Target Genes  

PubMed Central

MicroRNAs are endogenous small noncoding RNAs which play critical roles in gene regulation. Few wheat (Triticum aestivum L.) miRNA sequences are available in miRBase repertoire and knowledge of their biological functions related to biotic stress is limited. We identified 52 miRNAs, belonging to 19 families, from next-generation transcriptome sequence data based on homology search. One wheat specific novel miRNA was identified but could not be ascribed or assigned to any known miRNA family. Differentially expressed 22 miRNAs were found between susceptible and resistant wheat near-isogenic lines inoculated with leaf rust pathogen Puccinia triticina and compared with mock inoculated controls. Most miRNAs were more upregulated in susceptible NIL compared to resistant NIL. We identified 1306 potential target genes for these 52 miRNAs with vital roles in response to stimuli, signaling, and diverse metabolic and cellular processes. Gene ontology analysis showed 66, 20, and 35 target genes to be categorized into biological process, molecular function, and cellular component, respectively. A miRNA-mediated regulatory network revealed relationships among the components of the targetome. The present study provides insight into potential miRNAs with probable roles in leaf rust pathogenesis and their target genes in wheat which establish a foundation for future studies. PMID:25180085

Kumar, Dhananjay; Singh, Dharmendra; Kanodia, Pulkit; Prabhu, Kumble Vinod; Kumar, Manish; Mukhopadhyay, Kunal

2014-01-01

223

TGF? Inducible Early Gene-1 (TIEG1) and Cardiac Hypertrophy: Discovery and Characterization of a Novel Signaling Pathway  

PubMed Central

Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGF? inducible early gene (TIEG) null mouse implicatingTIEG1 in cardiac hypertrophy. The TIEG?/? knock-out mouse was studied. Male mice age 4–16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N =40) did not develop hypertrophy or fibrosis. The TIEG ?/? knock-out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG?/?, and an increase in wall thickness in TIEG?/? mice of (1.85 ±0.21 mm), compared to the control (1.13 ±0.15 mm, P< 0.04). Masson Trichrome staining demonstrated evidence of myocyte disarray and myofibroblast fibrosis. Microarray analysis of the left ventricles demonstrated that TIEG?/? heart tissues expressed a 13.81-fold increase in pituitary tumor-transforming gene-1 (Pttg1). An increase in Pttg1 and histone H3 protein levels were confirmed in the TIEG?/? mice hearts tissues. We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse. PMID:16888812

Rajamannan, Nalini M.; Subramaniam, Malayannan; Abraham, Theodore P.; Vasile, Vlad C.; Ackerman, Michael J.; Monroe, David G.; Chew, Teng-Leong; Spelsberg, Thomas C.

2014-01-01

224

Discovery of a Linear Peptide for Improving Tumor Targeting of Gene Products and Treatment of Distal Tumors by IL-12 Gene Therapy  

PubMed Central

Like many effective therapeutics, interleukin-12 (IL-12) therapy often causes side effects. Tumor targeted delivery may improve the efficacy and decrease the toxicity of systemic IL-12 treatments. In this study, a novel targeting approach was investigated. A secreted alkaline phosphatase (SEAP) reporter gene-based screening process was used to identify a mini-peptide which can be produced in vivo to target gene products to tumors. The coding region for the best peptide was inserted into an IL-12 gene to determine the antitumor efficacy. Affinity chromatography, mass spectrometry analysis, and binding studies were used to identify a receptor for this peptide. We discovered that the linear peptide VNTANST increased the tumor accumulation of the reporter gene products in five independent tumor models including one human xenogeneic model. The product from VNTANST-IL-12 fusion gene therapy increased accumulation of IL-12 in the tumor environment, and in three tumor models, VNTANST-IL-12 gene therapy inhibited distal tumor growth. In a spontaneous lung metastasis model, inhibition of metastatic tumor growth was improved compared to wild-type IL-12 gene therapy, and in a squamous cell carcinoma model, toxic liver lesions were reduced. The receptor for VNTANST was identified as vimentin. These results show the promise of using VNTANST to improve IL-12 treatments. PMID:21386825

Cutrera, Jeffry; Dibra, Denada; Xia, Xueqing; Hasan, Azeem; Reed, Scott; Li, Shulin

2011-01-01

225

Discovery of a novel human G protein-coupled receptor gene (GPR25) located on chromosome 1.  

PubMed

We amplified human genomic DNA by the polymerase chain reaction (PCR) using oligonucleotides based on the primary sequence of the genes encoding the somatostatin receptors (SSTR) and the somatostatin-like receptor gene SLC-1. One resultant DNA fragment was used to screen a genomic DNA library resulting in the isolation of a gene, GPR25, encoding an additional member of the G protein-coupled receptor family (GPCR). GPR25 is intronless throughout its open reading frame (ORF) and encodes a protein of 360 amino acids. The receptor encoded by GPR25 shares highest identity to the receptor encoded by GPR15, angiotensin II type 1A receptor, and somatostatin receptor 5. Northern analysis found no transcripts expressed in liver or any of the 12 brain regions analyzed. Fluorescence in situ hybridization analysis localized GPR25 to chromosome 1q32.1. PMID:9020062

Jung, B P; Nguyen, T; Kolakowski, L F; Lynch, K R; Heng, H H; George, S R; O'Dowd, B F

1997-01-01

226

Novel enabling technologies of gene isolation and plant transformation for improved crop protection  

SciTech Connect

Meeting the needs of agricultural producers requires the continued development of improved transgenic crop protection products. The completed project focused on developing novel enabling technologies of gene discovery and plant transformation to facilitate the generation of such products.

Torok, Tamas

2013-02-04

227

The Hubble Space Telescope Extragalactic Distance Scale Key Project XXIII The Discovery of Cepheids In NGC 3319  

E-print Network

The distance to NGC 3319 has been determined from Cepheid variable stars as part of the Hubble Space Telescope Key Project on the Extragalactic Distance Scale. Thirteen and four epochs of observations, using filters F555W (V) and F814W (I) respectively, were made with the Wide Field Planetary Camera 2. Thirty-three Cepheid variables between periods of 8 and 47 days were discovered. Adopting a Large Magellanic Cloud distance modulus of 18.50 +- 0.10 mag and extinction of E(V-I)=0.13 mag, a true reddening-corrected distance modulus (based on an analysis employing the ALLFRAME software package) of 30.78 +- 0.14 (random) +- 0.10 (systematic) mag and the extinction of E(V-I) = 0.06 mag were determined for NGC 3319. This galaxy is the last galaxy observed for the HST H0 Key Project.

Sakai, S; Kennicutt, R C; Graham, J A; Silbermann, N A; Mould, J R; Freedman, W L; Bresolin, F; Ford, H C; Gibson, B K; Han, M; Harding, P; Hössel, J G; Huchra, J P; Hughes, S M; Illingworth, G D; Kelson, D D; Macri, L M; Madore, B F; Phelps, R L; Saha, A; Sebo, K M; Stetson, P B; Turner, A; Sakai, Shoko; Ferrarese, Laura; Kennicutt, Robert C.; Graham, John A.; Mould, Jeremy R.; Freedman, Wendy L.; Bresolin, Fabio; Ford, Holland C.; Gibson, Brad K.; Han, Mingsheng; Harding, Paul; Hoessel, John G.; Huchra, John P.; Hughes, Shaun M.; Illingworth, Garth D.; Kelson, Daniel; Macri, Lucas; Madore, Barry F.; Phelps, Randy L.; Saha, Abhijit; Sebo, Kim M.; Stetson, Peter B.; Turner, Anne

1999-01-01

228

De Novo Transcriptome Analysis of an Aerial Microalga Trentepohlia jolithus: Pathway Description and Gene Discovery for Carbon Fixation and Carotenoid Biosynthesis  

PubMed Central

Background Algae in the order Trentepohliales have a broad geographic distribution and are generally characterized by the presence of abundant ?-carotene. The many monographs published to date have mainly focused on their morphology, taxonomy, phylogeny, distribution and reproduction; molecular studies of this order are still rare. High-throughput RNA sequencing (RNA-Seq) technology provides a powerful and efficient method for transcript analysis and gene discovery in Trentepohlia jolithus. Methods/Principal Findings Illumina HiSeq 2000 sequencing generated 55,007,830 Illumina PE raw reads, which were assembled into 41,328 assembled unigenes. Based on NR annotation, 53.28% of the unigenes (22,018) could be assigned to gene ontology classes with 54 subcategories and 161,451 functional terms. A total of 26,217 (63.44%) assembled unigenes were mapped to 128 KEGG pathways. Furthermore, a set of 5,798 SSRs in 5,206 unigenes and 131,478 putative SNPs were identified. Moreover, the fact that all of the C4 photosynthesis genes exist in T. jolithus suggests a complex carbon acquisition and fixation system. Similarities and differences between T. jolithus and other algae in carotenoid biosynthesis are also described in depth. Conclusions/Significance This is the first broad transcriptome survey for T. jolithus, increasing the amount of molecular data available for the class Ulvophyceae. As well as providing resources for functional genomics studies, the functional genes and putative pathways identified here will contribute to a better understanding of carbon fixation and fatty acid and carotenoid biosynthesis in T. jolithus. PMID:25254555

Li, Qianqian; Liu, Jianguo; Zhang, Litao; Liu, Qian

2014-01-01

229

Discovery of a Linear Peptide for Improving Tumor Targeting of Gene Products and Treatment of Distal Tumors by IL12 Gene Therapy  

Microsoft Academic Search

Like many effective therapeutics, interleukin-12 (IL-12) therapy often causes side effects. Tumor targeted delivery may improve the efficacy and decrease the toxicity of systemic IL-12 treatments. In this study, a novel targeting approach was investigated. A secreted alkaline phosphatase (SEAP) reporter gene-based screening process was used to identify a mini-peptide which can be produced in vivo to target gene products

Jeffry Cutrera; Denada Dibra; Xueqing Xia; Azeem Hasan; Scott Reed; Shulin Li

2011-01-01

230

Gene discovery by genome-wide CDS re-prediction and microarray-based transcriptional analysis in phytopathogen Xanthomonas campestris  

PubMed Central

Background One of the major tasks of the post-genomic era is "reading" genomic sequences in order to extract all the biological information contained in them. Although a wide variety of techniques is used to solve the gene finding problem and a number of prokaryotic gene-finding software are available, gene recognition in bacteria is far from being always straightforward. Results This study reported a thorough search for new CDS in the two published Xcc genomes. In the first, putative CDSs encoded in the two genomes were re-predicted using three gene finders, resulting in the identification of 2850 putative new CDSs. In the second, similarity searching was conducted and 278 CDSs were found to have homologs in other bacterial species. In the third, oligonucleotide microarray and RT-PCR analysis identified 147 CDSs with detectable mRNA transcripts. Finally, in-frame deletion and subsequent phenotype analysis of confirmed that Xcc_CDS002 encoding a novel SIR2-like domain protein is involved in virulence and Xcc_CDS1553 encoding a ArsR family transcription factor is involved in arsenate resistance. Conclusions Despite sophisticated approaches available for genome annotation, many cellular transcripts have remained unidentified so far in Xcc genomes. Through a combined strategy involving bioinformatic, postgenomic and genetic approaches, a reliable list of 306 new CDSs was identified and a more thorough understanding of some cellular processes was gained. PMID:21745409

2011-01-01

231

Public Versus Private Ownership of Scientific Discovery: Legal and Economic Analyses of the Implications of Human Gene Patents  

Microsoft Academic Search

his issue of Academic Medicine presents a collection of original scholarly articles and commentaries on the legal and economic rationales supporting— and opposing—patents on human gene sequences. In this introduction, we review the concerns that led us to invite these analyses from authors who are each distin- guished in their respective professions of the law, economics, medicine, research, and education.

DAVID KORN; STEPHEN J. HEINIG

2002-01-01

232

Gene discovery for comparative biology of parasitic and non-parasitic plants. A five-week molecular research immersion  

Microsoft Academic Search

As part of an NSF-funded initiative, biology students, primarily those in the early stages of their degree program, were recruited to participate in ongoing research alongside principle investigators. In this example, ten students were given five weeks of intensive training in molecular research methods, with the objective of cloning genes involved in core metabolic processes in the parasitic plant Cuscuta

Mark A. Schoenbeck

233

Functional Gene-Guided Discovery of Type II Polyketides from Culturable Actinomycetes Associated with Soft Coral Scleronephthya sp  

PubMed Central

Compared with the actinomycetes in stone corals, the phylogenetic diversity of soft coral-associated culturable actinomycetes is essentially unexplored. Meanwhile, the knowledge of the natural products from coral-associated actinomycetes is very limited. In this study, thirty-two strains were isolated from the tissue of the soft coral Scleronephthya sp. in the East China Sea, which were grouped into eight genera by 16S rDNA phylogenetic analysis: Micromonospora, Gordonia, Mycobacterium, Nocardioides, Streptomyces, Cellulomonas, Dietzia and Rhodococcus. 6 Micromonospora strains and 4 Streptomyces strains were found to be with the potential for producing aromatic polyketides based on the analysis of KS? (ketoacyl-synthase) gene in the PKS II (type II polyketides synthase) gene cluster. Among the 6 Micromonospora strains, angucycline cyclase gene was amplified in 2 strains (A5-1 and A6-2), suggesting their potential in synthesizing angucyclines e.g. jadomycin. Under the guidance of functional gene prediction, one jadomycin B analogue (7b, 13-dihydro-7-O-methyl jadomycin B) was detected in the fermentation broth of Micromonospora sp. strain A5-1. This study highlights the phylogenetically diverse culturable actinomycetes associated with the tissue of soft coral Scleronephthya sp. and the potential of coral-derived actinomycetes especially Micromonospora in producing aromatic polyketides. PMID:22880121

Sun, Wei; Peng, Chongsheng; Zhao, Yunyu; Li, Zhiyong

2012-01-01

234

Discovery of single nucleotide polymorphisms in candidate genes associated with fertility and production traits in Holstein cattle  

PubMed Central

Background Identification of single nucleotide polymorphisms (SNPs) for specific genes involved in reproduction might improve reliability of genomic estimates for these low-heritability traits. Semen from 550 Holstein bulls of high (? 1.7; n?=?288) or low (? ?2; n?=?262) daughter pregnancy rate (DPR) was genotyped for 434 candidate SNPs using the Sequenom MassARRAY® system. Three types of SNPs were evaluated: SNPs previously reported to be associated with reproductive traits or physically close to genetic markers for reproduction, SNPs in genes that are well known to be involved in reproductive processes, and SNPs in genes that are differentially expressed between physiological conditions in a variety of tissues associated in reproductive function. Eleven reproduction and production traits were analyzed. Results A total of 40 SNPs were associated (P?genes involved in the endocrine system, cell signaling, immune function and inhibition of apoptosis. A total of 10 genes were regulated by estradiol. In addition, 22 SNPs were associated with heifer conception rate, 33 with cow conception rate, 36 with productive life, 34 with net merit, 23 with milk yield, 19 with fat yield, 13 with fat percent, 19 with protein yield, 22 with protein percent, and 13 with somatic cell score. The allele substitution effect for SNPs associated with heifer conception rate, cow conception rate, productive life and net merit were in the same direction as for DPR. Allele substitution effects for several SNPs associated with production traits were in the opposite direction as DPR. Nonetheless, there were 29 SNPs associated with DPR that were not negatively associated with production traits. Conclusion SNPs in a total of 40 genes associated with DPR were identified as well as SNPs for other traits. It might be feasible to include these SNPs into genomic tests of reproduction and other traits. The genes associated with DPR are likely to be important for understanding the physiology of reproduction. Given the large number of SNPs associated with DPR that were not negatively associated with production traits, it should be possible to select for DPR without compromising production. PMID:23759029

2013-01-01

235

Scientific Discovery for All  

ERIC Educational Resources Information Center

The scientific discovery process comes alive for 70 minority students each year at Uniondale High School in New York where students have won top awards for "in-house" projects. Uniondale High School is in a middle-income school district where over 95% of students are from minority groups. Founded in 2000, the Uniondale High School Research Program…

Zaikowski, Lori; Lichtman, Paul; Quarless, Duncan

2007-01-01

236

Redesigning antidepressant drug discovery  

PubMed Central

Antidepressant drug discovery and development have been put on hold by many pharmaceutical companies. The main reason for this is the negative efficacy studies with novel specific drugs. Here I argue that the main obstacles are the absence of gene tests and biomarkers as an integral part of a diagnostic process. Further, too much emphasis has been put on validating drug candidates in animal models of psychiatric disorders. A more rapid transfer of drug candidates into human research is necessary to overcome current obstacles that prevent the discovery of next-generation antidepressants. PMID:24733967

Holsboer, Florian

2014-01-01

237

The Hubble Space Telescope Extragalactic Distance Scale Key Project. 1: The discovery of Cepheids and a new distance to M81  

NASA Technical Reports Server (NTRS)

We report on the discovery of 30 new Cepheids in the nearby galaxy M81 based on observations using the Hubble Space Telescope (HST). The periods of these Cepheids lie in the range of 10-55 days, based on 18 independent epochs using the HST wide-band F555W filter. The HST F555W and F785LP data have been transformed to the Cousins standard V and I magnitude system using a ground-based calibration. Apparent period-luminosity relations at V and I were constructed, from which apparent distance moduli were measured with respect to assumed values of mu(sub 0) = 18.50 mag and E(B - V) = 0.10 mag for the Large Magellanic Cloud. The difference in the apparent V and I moduli yields a measure of the difference in the total mean extinction between the M81 and the LMC Cepheid samples. A low total mean extinction to the M81 sample of E(B - V) = 0.03 +/- 0.05 mag is obtained. The true distance modulus to M81 is determined to be 27.80 +/- 0.20 mag, corresponding to a distance of 3.63 +/- 0.34 Mpc. These data illustrate that with an optimal (power-law) sampling strategy, the HST provides a powerful tool for the discovery of extragalactic Cepheids and their application to the distance scale. M81 is the first calibrating galaxy in the target sample of the HST Key Project on the Extragalactic Distance Scale, the ultimate aim of which is to provide a value of the Hubble constant to 10% accuracy.

Freedman, Wendy L.; Hughes, Shaun M.; Madore, Barry F.; Mould, Jeremy R.; Lee, Myung Gyoon; Stetson, Peter; Kennicutt, Robert C.; Turner, Anne; Ferrarese, Laura; Ford, Holland

1994-01-01

238

Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.  

PubMed

We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six new genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN. PMID:25305756

Kiryluk, Krzysztof; Li, Yifu; Scolari, Francesco; Sanna-Cherchi, Simone; Choi, Murim; Verbitsky, Miguel; Fasel, David; Lata, Sneh; Prakash, Sindhuri; Shapiro, Samantha; Fischman, Clara; Snyder, Holly J; Appel, Gerald; Izzi, Claudia; Viola, Battista Fabio; Dallera, Nadia; Del Vecchio, Lucia; Barlassina, Cristina; Salvi, Erika; Bertinetto, Francesca Eleonora; Amoroso, Antonio; Savoldi, Silvana; Rocchietti, Marcella; Amore, Alessandro; Peruzzi, Licia; Coppo, Rosanna; Salvadori, Maurizio; Ravani, Pietro; Magistroni, Riccardo; Ghiggeri, Gian Marco; Caridi, Gianluca; Bodria, Monica; Lugani, Francesca; Allegri, Landino; Delsante, Marco; Maiorana, Mariarosa; Magnano, Andrea; Frasca, Giovanni; Boer, Emanuela; Boscutti, Giuliano; Ponticelli, Claudio; Mignani, Renzo; Marcantoni, Carmelita; Di Landro, Domenico; Santoro, Domenico; Pani, Antonello; Polci, Rosaria; Feriozzi, Sandro; Chicca, Silvana; Galliani, Marco; Gigante, Maddalena; Gesualdo, Loreto; Zamboli, Pasquale; Battaglia, Giovanni Giorgio; Garozzo, Maurizio; Maixnerová, Dita; Tesar, Vladimir; Eitner, Frank; Rauen, Thomas; Floege, Jürgen; Kovacs, Tibor; Nagy, Judit; Mucha, Krzysztof; P?czek, Leszek; Zaniew, Marcin; Mizerska-Wasiak, Ma?gorzata; Roszkowska-Blaim, Maria; Pawlaczyk, Krzysztof; Gale, Daniel; Barratt, Jonathan; Thibaudin, Lise; Berthoux, Francois; Canaud, Guillaume; Boland, Anne; Metzger, Marie; Panzer, Ulf; Suzuki, Hitoshi; Goto, Shin; Narita, Ichiei; Caliskan, Yasar; Xie, Jingyuan; Hou, Ping; Chen, Nan; Zhang, Hong; Wyatt, Robert J; Novak, Jan; Julian, Bruce A; Feehally, John; Stengel, Benedicte; Cusi, Daniele; Lifton, Richard P; Gharavi, Ali G

2014-11-01

239

Transcriptome Analysis of the Portunus trituberculatus: De Novo Assembly, Growth-Related Gene Identification and Marker Discovery  

PubMed Central

Background The swimming crab, Portunus trituberculatus, is an important farmed species in China, has been attracting extensive studies, which require more and more genome background knowledge. To date, the sequencing of its whole genome is unavailable and transcriptomic information is also scarce for this species. In the present study, we performed de novo transcriptome sequencing to produce a comprehensive transcript dataset for major tissues of Portunus trituberculatus by the Illumina paired-end sequencing technology. Results Total RNA was isolated from eyestalk, gill, heart, hepatopancreas and muscle. Equal quantities of RNA from each tissue were pooled to construct a cDNA library. Using the Illumina paired-end sequencing technology, we generated a total of 120,137 transcripts with an average length of 1037 bp. Further assembly analysis showed that all contigs contributed to 87,100 unigenes, of these, 16,029 unigenes (18.40% of the total) can be matched in the GenBank non-redundant database. Potential genes and their functions were predicted by GO, KEGG pathway mapping and COG analysis. Based on our sequence analysis and published literature, many putative genes with fundamental roles in growth and muscle development, including actin, myosin, tropomyosin, troponin and other potentially important candidate genes were identified for the first time in this specie. Furthermore, 22,673 SSRs and 66,191 high-confidence SNPs were identified in this EST dataset. Conclusion The transcriptome provides an invaluable new data for a functional genomics resource and future biological research in Portunus trituberculatus. The data will also instruct future functional studies to manipulate or select for genes influencing growth that should find practical applications in aquaculture breeding programs. The molecular markers identified in this study will provide a material basis for future genetic linkage and quantitative trait loci analyses, and will be essential for accelerating aquaculture breeding programs with this species. PMID:24722690

Lv, Jianjian; Liu, Ping; Gao, Baoquan; Wang, Yu; Wang, Zheng; Chen, Ping; Li, Jian

2014-01-01

240

Discovery of genes implicated in whirling disease infection and resistance in rainbow trout using genome-wide expression profiling  

PubMed Central

Background Whirling disease, caused by the pathogen Myxobolus cerebralis, afflicts several salmonid species. Rainbow trout are particularly susceptible and may suffer high mortality rates. The disease is persistent and spreading in hatcheries and natural waters of several countries, including the U.S.A., and the economic losses attributed to whirling disease are substantial. In this study, genome-wide expression profiling using cDNA microarrays was conducted for resistant Hofer and susceptible Trout Lodge rainbow trout strains following pathogen exposure with the primary objective of identifying specific genes implicated in whirling disease resistance. Results Several genes were significantly up-regulated in skin following pathogen exposure for both the resistant and susceptible rainbow trout strains. For both strains, response to infection appears to be linked with the interferon system. Expression profiles for three genes identified with microarrays were confirmed with qRT-PCR. Ubiquitin-like protein 1 was up-regulated over 100 fold and interferon regulating factor 1 was up-regulated over 15 fold following pathogen exposure for both strains. Expression of metallothionein B, which has known roles in inflammation and immune response, was up-regulated over 5 fold in the resistant Hofer strain but was unchanged in the susceptible Trout Lodge strain following pathogen exposure. Conclusion The present study has provided an initial view into the genetic basis underlying immune response and resistance of rainbow trout to the whirling disease parasite. The identified genes have allowed us to gain insight into the molecular mechanisms implicated in salmonid immune response and resistance to whirling disease infection. PMID:18218127

Baerwald, Melinda R; Welsh, Amy B; Hedrick, Ronald P; May, Bernie

2008-01-01

241

Discovery of consensus gene signature and intermodular connectivity defining self-renewal of human embryonic stem cells.  

PubMed

Molecular markers defining self-renewing pluripotent embryonic stem cells (ESCs) have been identified by relative comparisons between undifferentiated and differentiated cells. Most of analysis has been done under a specific differentiation condition that may present significantly different molecular changes over others. Therefore, it is currently unclear if there are true consensus markers defining undifferentiated human ESCs (hESCs). To identify a set of key genes consistently altered during differentiation of hESCs regardless of differentiation conditions, we have performed microarray analysis on undifferentiated hESCs (H1 and H9) and differentiated EBs and validated our results using publicly available expression array datasets. We constructed consensus modules by Weighted Gene Coexpression Network Analysis and discovered novel markers that are consistently present in undifferentiated hESCs under various differentiation conditions. We have validated top markers (downregulated: LCK, KLKB1, and SLC7A3; upregulated: RhoJ, Zeb2, and Adam12) upon differentiation. Functional validation analysis of LCK in self-renewal of hESCs using LCK inhibitor or gene silencing with siLCK resulted in a loss of undifferentiation characteristics-morphological change, reduced alkaline phosphatase activity, and pluripotency gene expression, demonstrating a potential functional role of LCK in self-renewal of hESCs. We have designated hESC markers to interactive networks in the genome, identifying possible interacting partners and showing how new markers relate to each other. Furthermore, comparison of these datasets with available datasets from induced pluripotent stem cells (iPSCs) revealed that the level of these newly identified markers was correlated to the establishment of iPSCs, which may imply a potential role of these markers in gaining of cellular potency. PMID:24519983

Kim, Jeffrey J; Khalid, Omar; Namazi, AmirHosien; Tu, Thanh G; Elie, Omid; Lee, Connie; Kim, Yong

2014-06-01

242

Discovery of Seven Novel Mammalian and Avian Coronaviruses in the Genus Deltacoronavirus Supports Bat Coronaviruses as the Gene Source of Alphacoronavirus and Betacoronavirus and Avian Coronaviruses as the Gene Source of Gammacoronavirus and Deltacoronavirus  

PubMed Central

Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination. PMID:22278237

Woo, Patrick C. Y.; Lau, Susanna K. P.; Lam, Carol S. F.; Lau, Candy C. Y.; Tsang, Alan K. L.; Lau, John H. N.; Bai, Ru; Teng, Jade L. L.; Tsang, Chris C. C.; Wang, Ming; Zheng, Bo-Jian; Chan, Kwok-Hung

2012-01-01

243

Genetic Predictors of Adverse Radiotherapy Effects: The Gene-PARE project  

SciTech Connect

Purpose: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal. Methods and Materials: A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work. Results: Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy. Conclusions: It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis.

Ho, Alice Y. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Atencio, David P. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Peters, Sheila [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Stock, Richard G.; Cesaretti, Jamie A.; Green, Sheryl [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States); Formenti, Silvia C. [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States); Haffty, Bruce [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT (United States); Drumea, Karen [Department of Oncology, Rambam Medical Center, Haifa (Israel); Leitzin, Larisa M.D. [Department of Oncology, Rambam Medical Center, Haifa (Israel); Kuten, Abraham [Department of Oncology, Rambam Medical Center, Haifa (Israel); Azria, David [Department of Radiation Oncology, CRLC Val d'Aurelle, Montpellier (France); Ozsahin, Mahmut [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne (Switzerland); Overgaard, Jens; Andreassen, Christian N. [Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus (Denmark); Trop, Cynthia S. [Department of Urology, Bronx VA Medical Center, Bronx, NY (United States); Park, Janelle [Department of Radiation Oncology, Bronx VA Medical Center, Bronx, NY (United States); Rosenstein, Barry S. [Department of Radiation Oncology, Mount Sinai School of Medicine, New York, NY (United States)]|[Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York NY (United States)]|[Department of Dermatology, Mount Sinai School of Medicine, New York, NY (United States)]|[Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States)]. E-mail: barry.rosenstein@mssm.edu

2006-07-01

244

Discovery Channel  

E-print Network

://dsc.discovery.com/news/briefs/20051226/electronics_tec.html 3 of 3 12/27/2005 10:42 PM 23 Dec 2005 Early Image of Jesus Found 23 Dec 2005-world media and entertainment company. #12;Discovery Channel :: News :: Electronics Stretch Out http of your body in a natural way," said John Rogers of the University of Illinois at Urbana-Champaign. Rogers

Rogers, John A.

245

Discovery Bottles  

NSDL National Science Digital Library

Discover discovery bottles! These wide-mouth plastic containers of any size filled with objects of different kinds can be terrific tools for science explorations and a great way to cultivate science minds in a K--2 science classroom. In addition, the author has found them to be a useful, inexpensive, and engaging way to help students develop skills in making predictions, observations, and comparisons. Here she shares a few of her favorite physical science lesson ideas using discovery bottles.

Watson, Sandy

2008-07-01

246

Gene discovery for enzymes involved in limonene modification or utilization by the mountain pine beetle-associated pathogen Grosmannia clavigera.  

PubMed

To successfully colonize and eventually kill pine trees, Grosmannia clavigera (Gs cryptic species), the main fungal pathogen associated with the mountain pine beetle (Dendroctonus ponderosae), has developed multiple mechanisms to overcome host tree chemical defenses, of which terpenoids are a major component. In addition to a monoterpene efflux system mediated by a recently discovered ABC transporter, Gs has genes that are highly induced by monoterpenes and that encode enzymes that modify or utilize monoterpenes [especially (+)-limonene]. We showed that pine-inhabiting Ophiostomale fungi are tolerant to monoterpenes, but only a few, including Gs, are known to utilize monoterpenes as a carbon source. Gas chromatography-mass spectrometry (GC-MS) revealed that Gs can modify (+)-limonene through various oxygenation pathways, producing carvone, p-mentha-2,8-dienol, perillyl alcohol, and isopiperitenol. It can also degrade (+)-limonene through the C-1-oxygenated pathway, producing limonene-1,2-diol as the most abundant intermediate. Transcriptome sequencing (RNA-seq) data indicated that Gs may utilize limonene 1,2-diol through beta-oxidation and then valine and tricarboxylic acid (TCA) metabolic pathways. The data also suggested that at least two gene clusters, located in genome contigs 108 and 161, were highly induced by monoterpenes and may be involved in monoterpene degradation processes. Further, gene knockouts indicated that limonene degradation required two distinct Baeyer-Villiger monooxygenases (BVMOs), an epoxide hydrolase and an enoyl coenzyme A (enoyl-CoA) hydratase. Our work provides information on enzyme-mediated limonene utilization or modification and a more comprehensive understanding of the interaction between an economically important fungal pathogen and its host's defense chemicals. PMID:24837377

Wang, Ye; Lim, Lynette; Madilao, Lina; Lah, Ljerka; Bohlmann, Joerg; Breuil, Colette

2014-08-01

247

Automated conserved non-coding sequence (CNS) discovery reveals differences in gene content and promoter evolution among grasses  

PubMed Central

Conserved non-coding sequences (CNS) are islands of non-coding sequence that, like protein coding exons, show less divergence in sequence between related species than functionless DNA. Several CNSs have been demonstrated experimentally to function as cis-regulatory regions. However, the specific functions of most CNSs remain unknown. Previous searches for CNS in plants have either anchored on exons and only identified nearby sequences or required years of painstaking manual annotation. Here we present an open source tool that can accurately identify CNSs between any two related species with sequenced genomes, including both those immediately adjacent to exons and distal sequences separated by >12 kb of non-coding sequence. We have used this tool to characterize new motifs, associate CNSs with additional functions, and identify previously undetected genes encoding RNA and protein in the genomes of five grass species. We provide a list of 15,363 orthologous CNSs conserved across all grasses tested. We were also able to identify regulatory sequences present in the common ancestor of grasses that have been lost in one or more extant grass lineages. Lists of orthologous gene pairs and associated CNSs are provided for reference inbred lines of arabidopsis, Japonica rice, foxtail millet, sorghum, brachypodium, and maize. PMID:23874343

Turco, Gina; Schnable, James C.; Pedersen, Brent; Freeling, Michael

2013-01-01

248

Automated Discovery of Tissue-Targeting Enhancers and Transcription Factors from Binding Motif and Gene Function Data  

PubMed Central

Identifying enhancers regulating gene expression remains an important and challenging task. While recent sequencing-based methods provide epigenomic characteristics that correlate well with enhancer activity, it remains onerous to comprehensively identify all enhancers across development. Here we introduce a computational framework to identify tissue-specific enhancers evolving under purifying selection. First, we incorporate high-confidence binding site predictions with target gene functional enrichment analysis to identify transcription factors (TFs) likely functioning in a particular context. We then search the genome for clusters of binding sites for these TFs, overcoming previous constraints associated with biased manual curation of TFs or enhancers. Applying our method to the placenta, we find 33 known and implicate 17 novel TFs in placental function, and discover 2,216 putative placenta enhancers. Using luciferase reporter assays, 31/36 (86%) tested candidates drive activity in placental cells. Our predictions agree well with recent epigenomic data in human and mouse, yet over half our loci, including 7/8 (87%) tested regions, are novel. Finally, we establish that our method is generalizable by applying it to 5 additional tissues: heart, pancreas, blood vessel, bone marrow, and liver. PMID:24499934

Tuteja, Geetu; Moreira, Karen Betancourt; Chung, Tisha; Chen, Jenny; Wenger, Aaron M.; Bejerano, Gill

2014-01-01

249

High-Throughput Discovery of Mutations in Tef Semi-Dwarfing Genes by Next-Generation Sequencing Analysis  

PubMed Central

Tef (Eragrostis tef) is a major cereal crop in Ethiopia. Lodging is the primary constraint to increasing productivity in this allotetraploid species, accounting for losses of ?15–45% in yield each year. As a first step toward identifying semi-dwarf varieties that might have improved lodging resistance, an ?6× fosmid library was constructed and used to identify both homeologues of the dw3 semi-dwarfing gene of Sorghum bicolor. An EMS mutagenized population, consisting of ?21,210 tef plants, was planted and leaf materials were collected into 23 superpools. Two dwarfing candidate genes, homeologues of dw3 of sorghum and rht1 of wheat, were sequenced directly from each superpool with 454 technology, and 120 candidate mutations were identified. Out of 10 candidates tested, six independent mutations were validated by Sanger sequencing, including two predicted detrimental mutations in both dw3 homeologues with a potential to improve lodging resistance in tef through further breeding. This study demonstrates that high-throughput sequencing can identify potentially valuable mutations in under-studied plant species like tef and has provided mutant lines that can now be combined and tested in breeding programs for improved lodging resistance. PMID:22904035

Zhu, Qihui; Smith, Shavannor M.; Ayele, Mulu; Yang, Lixing; Jogi, Ansuya; Chaluvadi, Srinivasa R.; Bennetzen, Jeffrey L.

2012-01-01

250

The Extragalactic Distance Scale Key Project; 8, The Discovery of Cepheids and a New Distance to NGC 3621 Using the Hubble Space Telescope  

E-print Network

We report on the discovery of Cepheids in the field spiral galaxy NGC 3621, based on observations made with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope (HST). NGC 3621 is one of 18 galaxies observed as a part of The HST Key Project on the Extragalactic Distance Scale, which aims to measure the Hubble constant to 10% accuracy. Sixty-nine Cepheids with periods in the range 9--60 days were observed over 12 epochs using the F555W filter, and 4 epochs using the F814W filter. The HST F555W and F814W data were transformed to the Johnson V and Kron-Cousins I magnitude systems, respectively. Photometry was performed using two independent packages, DAOPHOT II/ALLFRAME and DoPHOT. Period-luminosity relations in the V and I bands were constructed using 36 fairly isolated Cepheids present in our set of 69 variables. Extinction-corrected distance moduli relative to the LMC of 10.63 +/- 0.07 mag and 10.56 +/- 0.10 mag were obtained using the ALLFRAME and DoPHOT data, respectively. True distance...

Rawson, D M; Mould, J R; Huchra, J P; Freedman, W L; Kennicutt, R C; Ferrarese, L; Ford, H C; Graham, J A; Harding, P; Han, M; Hill, R J; Hössel, J G; Hughes, S M G; Illingworth, G D; Madore, B F; Phelps, R L; Saha, A; Sakai, S; Silbermann, N A; Stetson, P B; Rawson, Daya M.; Macri, Lucas M.; Mould, Jeremy R.; Huchra, John P.; Freedman, Wendy L.; Kennicutt, Robert C.; Ferrarese, Laura; Ford, Holland C.; Graham, John A.; Harding, Paul; Han, Mingsheng; Hill, Robert J.; Hoessel, John G.; Hughes, Shaun M. G.; Illingworth, Garth D.; Madore, Barry F.; Phelps, Randy L.; Saha, Abhijit; Sakai, Shoko; Silbermann, Nancy A.; Stetson, Peter B.

1997-01-01

251

Development of an integrated transcript sequence database and a gene expression atlas for gene discovery and analysis in switchgrass (Panicum virgatum L.).  

PubMed

Switchgrass (Panicum virgatum L.) is a perennial C4 grass with the potential to become a major bioenergy crop. To help realize this potential, a set of RNA-based resources were developed. Expressed sequence tags (ESTs) were generated from two tetraploid switchgrass genotypes, Alamo AP13 and Summer VS16. Over 11.5 million high-quality ESTs were generated with 454 sequencing technology, and an additional 169 079 Sanger sequences were obtained from the 5' and 3' ends of 93 312 clones from normalized, full-length-enriched cDNA libraries. AP13 and VS16 ESTs were assembled into 77 854 and 30 524 unique transcripts (unitranscripts), respectively, using the Newbler and pave programs. Published Sanger-ESTs (544 225) from Alamo, Kanlow, and 15 other cultivars were integrated with the AP13 and VS16 assemblies to create a universal switchgrass gene index (PviUT1.2) with 128 058 unitranscripts, which were annotated for function. An Affymetrix cDNA microarray chip (Pvi_cDNAa520831) containing 122 973 probe sets was designed from PviUT1.2 sequences, and used to develop a Gene Expression Atlas for switchgrass (PviGEA). The PviGEA contains quantitative transcript data for all major organ systems of switchgrass throughout development. We developed a web server that enables flexible, multifaceted analyses of PviGEA transcript data. The PviGEA was used to identify representatives of all known genes in the phenylpropanoid-monolignol biosynthesis pathway. PMID:23289674

Zhang, Ji-Yi; Lee, Yi-Ching; Torres-Jerez, Ivone; Wang, Mingyi; Yin, Yanbin; Chou, Wen-Chi; He, Ji; Shen, Hui; Srivastava, Avinash C; Pennacchio, Christa; Lindquist, Erika; Grimwood, Jane; Schmutz, Jeremy; Xu, Ying; Sharma, Manoj; Sharma, Rita; Bartley, Laura E; Ronald, Pamela C; Saha, Malay C; Dixon, Richard A; Tang, Yuhong; Udvardi, Michael K

2013-04-01

252

Discovery of potential new gene variants and inflammatory cytokine associations with fibromyalgia syndrome by whole exome sequencing.  

PubMed

Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder affecting 2% to 5% of the general population. Both genetic and environmental factors may be involved. To ascertain in an unbiased manner which genes play a role in the disorder, we performed complete exome sequencing on a subset of FMS patients. Out of 150 nuclear families (trios) DNA from 19 probands was subjected to complete exome sequencing. Since >80,000 SNPs were found per proband, the data were further filtered, including analysis of those with stop codons, a rare frequency (<2.5%) in the 1000 Genomes database, and presence in at least 2/19 probands sequenced. Two nonsense mutations, W32X in C11orf40 and Q100X in ZNF77 among 150 FMS trios had a significantly elevated frequency of transmission to affected probands (p?=?0.026 and p?=?0.032, respectively) and were present in a subset of 13% and 11% of FMS patients, respectively. Among 9 patients bearing more than one of the variants we have described, 4 had onset of symptoms between the ages of 10 and 18. The subset with the C11orf40 mutation had elevated plasma levels of the inflammatory cytokines, MCP-1 and IP-10, compared with unaffected controls or FMS patients with the wild-type allele. Similarly, patients with the ZNF77 mutation have elevated levels of the inflammatory cytokine, IL-12, compared with controls or patients with the wild type allele. Our results strongly implicate an inflammatory basis for FMS, as well as specific cytokine dysregulation, in at least 35% of our FMS cohort. PMID:23762283

Feng, Jinong; Zhang, Zhifang; Wu, Xiwei; Mao, Allen; Chang, Frances; Deng, Xutao; Gao, Harry; Ouyang, Ching; Dery, Kenneth J; Le, Keith; Longmate, Jeffrey; Marek, Claudia; St Amand, R Paul; Krontiris, Theodore G; Shively, John E

2013-01-01

253

Developmental Gene Discovery in a Hemimetabolous Insect: De Novo Assembly and Annotation of a Transcriptome for the Cricket Gryllus bimaculatus  

PubMed Central

Most genomic resources available for insects represent the Holometabola, which are insects that undergo complete metamorphosis like beetles and flies. In contrast, the Hemimetabola (direct developing insects), representing the basal branches of the insect tree, have very few genomic resources. We have therefore created a large and publicly available transcriptome for the hemimetabolous insect Gryllus bimaculatus (cricket), a well-developed laboratory model organism whose potential for functional genetic experiments is currently limited by the absence of genomic resources. cDNA was prepared using mRNA obtained from adult ovaries containing all stages of oogenesis, and from embryo samples on each day of embryogenesis. Using 454 Titanium pyrosequencing, we sequenced over four million raw reads, and assembled them into 21,512 isotigs (predicted transcripts) and 120,805 singletons with an average coverage per base pair of 51.3. We annotated the transcriptome manually for over 400 conserved genes involved in embryonic patterning, gametogenesis, and signaling pathways. BLAST comparison of the transcriptome against the NCBI non-redundant protein database (nr) identified significant similarity to nr sequences for 55.5% of transcriptome sequences, and suggested that the transcriptome may contain 19,874 unique transcripts. For predicted transcripts without significant similarity to known sequences, we assessed their similarity to other orthopteran sequences, and determined that these transcripts contain recognizable protein domains, largely of unknown function. We created a searchable, web-based database to allow public access to all raw, assembled and annotated data. This database is to our knowledge the largest de novo assembled and annotated transcriptome resource available for any hemimetabolous insect. We therefore anticipate that these data will contribute significantly to more effective and higher-throughput deployment of molecular analysis tools in Gryllus. PMID:23671567

Zeng, Victor; Ewen-Campen, Ben; Horch, Hadley W.; Roth, Siegfried; Mito, Taro; Extavour, Cassandra G.

2013-01-01

254

Optical Projection Tomography as a Tool for 3D Microscopy and Gene Expression Studies  

NASA Astrophysics Data System (ADS)

Current techniques for three-dimensional (3D) optical microscopy (deconvolution, confocal microscopy, and optical coherence tomography) generate 3D data by ``optically sectioning'' the specimen. This places severe constraints on the maximum thickness of a specimen that can be imaged. We have developed a microscopy technique that uses optical projection tomography (OPT) to produce high-resolution 3D images of both fluorescent and nonfluorescent biological specimens with a thickness of up to 15 millimeters. OPT microscopy allows the rapid mapping of the tissue distribution of RNA and protein expression in intact embryos or organ systems and can therefore be instrumental in studies of developmental biology or gene function.

Sharpe, James; Ahlgren, Ulf; Perry, Paul; Hill, Bill; Ross, Allyson; Hecksher-Sørensen, Jacob; Baldock, Richard; Davidson, Duncan

2002-04-01

255

Accidental Discoveries  

NSDL National Science Digital Library

The students will understand that science theories change in the face of new evidence, but those changes can be slow in coming. To download the lesson plan as a pdf, see the document below. Students willResearch scientific discoveries that happened by accident in the past and learn how gamma-rays were discovered by 20th century scientists

2010-01-01

256

Space Discovery.  

ERIC Educational Resources Information Center

Describes one teacher's experience taking Space Discovery courses that were sponsored by the United States Space Foundation (USSF). These courses examine the history of space science, theory of orbits and rocketry, the effects of living in outer space on humans, and space weather. (DDR)

Blackman, Joan

1998-01-01

257

Characterisation of the wheat (triticum aestivum L.) transcriptome by de novo assembly for the discovery of phosphate starvation-responsive genes: gene expression in Pi-stressed wheat  

PubMed Central

Background Phosphorus (P) is an essential macronutrient for plant growth and development. To modulate their P homeostasis, plants must balance P uptake, mobilisation, and partitioning to various organs. Despite the worldwide importance of wheat as a cultivated food crop, molecular mechanisms associated with phosphate (Pi) starvation in wheat remain unclear. To elucidate these mechanisms, we used RNA-Seq methods to generate transcriptome profiles of the wheat variety ‘Chinese Spring’ responding to 10 days of Pi starvation. Results We carried out de novo assembly on 73.8 million high-quality reads generated from RNA-Seq libraries. We then constructed a transcript dataset containing 29,617 non-redundant wheat transcripts, comprising 15,047 contigs and 14,570 non-redundant full-length cDNAs from the TriFLDB database. When compared with barley full-length cDNAs, 10,656 of the 15,047 contigs were unalignable, suggesting that many might be distinct from barley transcripts. The average expression level of the contigs was lower than that of the known cDNAs, implying that these contigs included transcripts that were rarely represented in the full-length cDNA library. Within the non-redundant transcript set, we identified 892–2,833 responsive transcripts in roots and shoots, corresponding on average to 23.4% of the contigs not covered by cDNAs in TriFLDB under Pi starvation. The relative expression level of the wheat IPS1 (Induced by Phosphate Starvation 1) homologue, TaIPS1, was 341-fold higher in roots and 13-fold higher in shoots; this finding was further confirmed by qRT-PCR analysis. A comparative analysis of the wheat- and rice-responsive transcripts for orthologous genes under Pi-starvation revealed commonly upregulated transcripts, most of which appeared to be involved in a general response to Pi starvation, namely, an IPS1-mediated signalling cascade and its downstream functions such as Pi remobilisation, Pi uptake, and changes in Pi metabolism. Conclusions Our transcriptome profiles demonstrated the impact of Pi starvation on global gene expression in wheat. This study revealed that enhancement of the Pi-mediated signalling cascade using IPS1 is a potent adaptation mechanism to Pi starvation that is conserved in both wheat and rice and validated the effectiveness of using short-read next-generation sequencing data for wheat transcriptome analysis in the absence of reference genome information. PMID:23379779

2013-01-01

258

The Extragalactic Distance Scale Key Project VIII. The Discovery of Cepheids and a New Distance to NGC 3621 Using the Hubble Space Telescope  

E-print Network

We report on the discovery of Cepheids in the field spiral galaxy NGC 3621, based on observations made with the Wide Field and Planetary Camera 2 on board the Hubble Space Telescope (HST). NGC 3621 is one of 18 galaxies observed as a part of The HST Key Project on the Extragalactic Distance Scale, which aims to measure the Hubble constant to 10% accuracy. Sixty-nine Cepheids with periods in the range 9--60 days were observed over 12 epochs using the F555W filter, and 4 epochs using the F814W filter. The HST F555W and F814W data were transformed to the Johnson V and Kron-Cousins I magnitude systems, respectively. Photometry was performed using two independent packages, DAOPHOT II/ALLFRAME and DoPHOT. Period-luminosity relations in the V and I bands were constructed using 36 fairly isolated Cepheids present in our set of 69 variables. Extinction-corrected distance moduli relative to the LMC of 10.63 +/- 0.07 mag and 10.56 +/- 0.10 mag were obtained using the ALLFRAME and DoPHOT data, respectively. True distance moduli of 29.13 +/- 0.18 mag and 29.06 +/- 0.18 mag, corresponding to distances of 6.3 Mpc and 6.1 Mpc, were obtained by assuming values of 18.50 +/- 0.10 mag for the distance modulus of the LMC and E(V-I) = 0.13 mag for the reddening of the LMC.

Daya M. Rawson; Lucas M. Macri; Jeremy R. Mould; John P. Huchra; Wendy L. Freedman; Robert C. Kennicutt; Laura Ferrarese; Holland C. Ford; John A. Graham; Paul Harding; Mingsheng Han; Robert J. Hill; John G. Hoessel; Shaun M. G. Hughes; Garth D. Illingworth; Barry F. Madore; Randy L. Phelps; Abhijit Saha; Shoko Sakai; Nancy A. Silbermann; Peter B. Stetson

1997-05-30

259

DOE “Discovery Across Texas” Project  

E-print Network

tranches of homes, from code-built to ?deep- green? homes Document consumer response to dynamic pricing models Determine the benefits of residential demand generation Determine the economic value of community-level energy storage and solar Determine... Smart appliances --- --- --- Yes HEM system --- --- --- Yes Load control (PCT adjustment) --- Yes (1-way) Yes (2-way) Yes (2-way) Solar panels --- --- --- Yes Energy storage system --- --- --- Yes * PEV charging station and lease vehicle...

Holloway, M.

2011-01-01

260

DFCI Gene Index Project: Genomic Databases for Plants, Animals, Protist, and Fungi from the Dana-Farber Cancer Institute  

DOE Data Explorer

The DFCI Gene Index Project creates databases for specific organisms. The goal for these databases is to provide an analysis of publicly available Expressed Sequence Transcripts (ESTs). ESTs are fragments of genes that were, at some time, copied from DNA to RNA. and gene sequence data to identify transcrips. The databases are in zipped files and free for download. The website also provides software and tools for use with the data, along with instructions from the website on how to link to background resources. The Gene Indices are organized into four categories: Animals, Plants, Protist, and Fungi.

261

Construction and evaluation of normalized cDNA libraries enriched with full-length sequences for rapid discovery of new genes from Sisal (Agave sisalana Perr.) different developmental stages.  

PubMed

To provide a resource of sisal-specific expressed sequence data and facilitate this powerful approach in new gene research, the preparation of normalized cDNA libraries enriched with full-length sequences is necessary. Four libraries were produced with RNA pooled from Agave sisalana multiple tissues to increase efficiency of normalization and maximize the number of independent genes by SMART™ method and the duplex-specific nuclease (DSN). This procedure kept the proportion of full-length cDNAs in the subtracted/normalized libraries and dramatically enhanced the discovery of new genes. Sequencing of 3875 cDNA clones of libraries revealed 3320 unigenes with an average insert length about 1.2 kb, indicating that the non-redundancy of libraries was about 85.7%. These unigene functions were predicted by comparing their sequences to functional domain databases and extensively annotated with Gene Ontology (GO) terms. Comparative analysis of sisal unigenes and other plant genomes revealed that four putative MADS-box genes and knotted-like homeobox (knox) gene were obtained from a total of 1162 full-length transcripts. Furthermore, real-time PCR showed that the characteristics of their transcripts mainly depended on the tight expression regulation of a number of genes during the leaf and flower development. Analysis of individual library sequence data indicated that the pooled-tissue approach was highly effective in discovering new genes and preparing libraries for efficient deep sequencing. PMID:23202944

Zhou, Wen-Zhao; Zhang, Yan-Mei; Lu, Jun-Ying; Li, Jun-Feng

2012-01-01

262

Construction and Evaluation of Normalized cDNA Libraries Enriched with Full-Length Sequences for Rapid Discovery of New Genes from Sisal (Agave sisalana Perr.) Different Developmental Stages  

PubMed Central

To provide a resource of sisal-specific expressed sequence data and facilitate this powerful approach in new gene research, the preparation of normalized cDNA libraries enriched with full-length sequences is necessary. Four libraries were produced with RNA pooled from Agave sisalana multiple tissues to increase efficiency of normalization and maximize the number of independent genes by SMART™ method and the duplex-specific nuclease (DSN). This procedure kept the proportion of full-length cDNAs in the subtracted/normalized libraries and dramatically enhanced the discovery of new genes. Sequencing of 3875 cDNA clones of libraries revealed 3320 unigenes with an average insert length about 1.2 kb, indicating that the non-redundancy of libraries was about 85.7%. These unigene functions were predicted by comparing their sequences to functional domain databases and extensively annotated with Gene Ontology (GO) terms. Comparative analysis of sisal unigenes and other plant genomes revealed that four putative MADS-box genes and knotted-like homeobox (knox) gene were obtained from a total of 1162 full-length transcripts. Furthermore, real-time PCR showed that the characteristics of their transcripts mainly depended on the tight expression regulation of a number of genes during the leaf and flower development. Analysis of individual library sequence data indicated that the pooled-tissue approach was highly effective in discovering new genes and preparing libraries for efficient deep sequencing. PMID:23202944

Zhou, Wen-Zhao; Zhang, Yan-Mei; Lu, Jun-Ying; Li, Jun-Feng

2012-01-01

263

Wyre Community Discovery Centre Wyre Community Discovery  

E-print Network

Wyre Community Discovery Centre Wyre Community Discovery Centre is an excellent example of low on the Go-Ape course or participate in learning activities at the Discovery Centre. A local initiative Discovery Centre. The £664,000 Centre will provide a base for the community to learn more about the local

264

Effective Dimension Reduction Using Sequential Projection Pursuit On Gene Expression Data for Cancer Classification  

SciTech Connect

Motiviation: Classification is a powerful tool for uncovering interesting phenomena, for example classes of cancer, in microarray data. Due to the small number of observations (n) in comparison to the number of variables (p), genes, classification on microarray data is challenging. Thus, multivariate dimension reduction techniques are commonly used as a precursor to classification of microarray data; typically this is principal component analysis (PCA) or singular value decomposition (SVD). Since PCA and SVD are concerned with explaining the variance-covariance structure of the data, they may not be the best choice when the between-cluster variance is smaller than the within-cluster variance. Recently an attractive alternative to PCA, sequential projection pursuit (SPP), has been introduced which is designed to elicit clustering tendencies in the data. Thus, in some cases SPP may be more appropriate when performing clustering or classification analysis. Results: We compare the performance of SPP to PCA on two cancer gene expression datasets related to leukemia and colon cancer. Using PCA and SPP to reduce the dimensionality of the data to m<

Webb-Robertson, Bobbie-Jo M.; Havre, Susan L.

2004-06-23

265

Discovery Channel: Extreme Engineering  

NSDL National Science Digital Library

Extreme Engineering is a program on the Discovery Channel that unveils "some of the most ambitious architectural plans of our times." The projects highlighted in each episode come from locations around the world. Some are in the planning stages, while others are only theoretical. This Web site serves as a companion to the television broadcasts and has interactive multimedia tours that offer a glimpse of what the projects would look like when completed. An underwater train tunnel linking New York and London, a massive skyscraper city in Tokyo, and a bridge over the Bering Strait are just some of the remarkable projects featured. The online elements are added after the corresponding episode is aired.

2005-12-21

266

Scientific Discovery for All  

NSDL National Science Digital Library

The scientific discovery process comes alive for 70 minority students each year at Uniondale High School in New York where students have won top awards for "in-house" projects. Students develop projects from an original idea that interests them, design the methodology, implement it, present results in written and oral format competitions and conferences, and propose and conduct further studies. The Uniondale program advisor and external mentors guide young investigators in "doing science" by instructing them in techniques, research ethics, and scientific integrity (NAS 1995), and advising students while they prepare research papers and presentations. This article describes the components of this successful program: careful recruitment; research projects that are devised by students; and recognition by the school, community, and outside entities.

Quarless, Duncan; Zaikowski, Lori; Lichtman, Paul

2007-03-01

267

The Extragalactic Distance Scale Key Project III. Teh discovery of Cephids and a New Distance to M101 Using the Hubble Space Telescope  

NASA Technical Reports Server (NTRS)

We report on the discovery of 29 cephid variables in the galaxy M101 after using the original Wide Field Camera (WFC 1) and the new Wide Field and Planetary Camera (WFPC 2) on the Hubble Space Telescope (HST), to observe a field in M101 at 14 independent epochs in F555W.

Kelson, Daniel D.; Madore, Barry

1994-01-01

268

2013 Update of the discoveries of nuclides  

E-print Network

The 2013 update of the discovery of nuclide project is presented. Details of the 12 new nuclides observed for the first time in 2013 are described. In addition, the discovery of 266Db has been included and the previous assignments of 6 other nuclides were changed. Overview tables of where and how nuclides were discovered have also been updated and are discussed.

M. Thoennessen

2014-02-07

269

The Hubble Space Telescope Extragalactic Distance Scale Key Project. 1: The discovery of Cepheids and a new distance to M81  

Microsoft Academic Search

We report on the discovery of 30 new Cepheids in the nearby galaxy M81 based on observations using the Hubble Space Telescope (HST). The periods of these Cepheids lie in the range of 10-55 days, based on 18 independent epochs using the HST wide-band F555W filter. The HST F555W and F785LP data have been transformed to the Cousins standard V

Wendy L. Freedman; Shaun M. Hughes; Barry F. Madore; Jeremy R. Mould; Myung Gyoon Lee; Peter Stetson; Robert C. Kennicutt; Anne Turner; Laura Ferrarese; Holland Ford; John A. Graham; Robert Hill; John G. Hoessel; John Huchra; Garth D. Illingworth

1994-01-01

270

The Extragalactic Distance Scale Key Project. III. The Discovery of Cepheids and a New Distance to M101 Using the Hubble Space Telescope  

Microsoft Academic Search

We report on the discovery of 29 Cepheid variables in the galaxy M101 using the original Wide Field Camera (WFC) and the new Wide Field and Planetary Camera 2 (WFPC2) on the Hubble Space Telescope. We observed a field in M101 at 17 independent epochs in V (F555W), five epochs in I (F785LP\\/ F814W), and one epoch in B (F439W),

Daniel D. Kelson; Garth D. Illingworth; Wendy F. Freedman; John A. Graham; Robert Hill; Barry F. Madore; Abhijit Saha; Peter B. Stetson; Robert C. Kennicutt Jr.; Jeremy R. Mould; Shaun M. Hughes; Laura Ferrarese; Randy Phelps; Anne Turner; Kem H. Cook; Holland Ford; John G. Hoessel; John Huchra

1996-01-01

271

The discovery that RNA interference (RNAi) and related small-RNA-mediated pathways have central roles in the silencing of gene expression  

E-print Network

The discovery that RNA interference (RNAi) and related small-RNA- mediated pathways have central, and their generation depends on the ribonuclease (RNase) Dicer3 . These small RNAs subsequently asso- ciate RNases: Dicer, which functions as a molec- ular ruler in siRNA and miRNA biogenesis; and Argonaute

Cai, Long

272

Wildlife Discovery.  

ERIC Educational Resources Information Center

This pocket folder of instructional materials is designed to introduce youths aged 9 to 12 to the nature and needs of wildlife and to give children the opportunity to search for wildlife and their signs. The document includes a member's guide, a leader's guide, field record forms, and wildlife project materials. The illustrated 4-H member's guide…

Silverman, Beth; And Others

273

Interaction of insulin and PPAR-? genes in Alzheimer's disease: the Epistasis Project.  

PubMed

Altered glucose metabolism has been described in Alzheimer's disease (AD). We re-investigated the interaction of the insulin (INS) and the peroxisome proliferator-activated receptor alpha (PPARA) genes in AD risk in the Epistasis Project, including 1,757 AD cases and 6,294 controls. Allele frequencies of both SNPs (PPARA L162V, INS intron 0 A/T) differed between Northern Europeans and Northern Spanish. The PPARA 162LL genotype increased AD risk in Northern Europeans (p = 0.04), but not in Northern Spanish (p = 0.2). There was no association of the INS intron 0 TT genotype with AD. We observed an interaction on AD risk between PPARA 162LL and INS intron 0 TT genotypes in Northern Europeans (Synergy factor 2.5, p = 0.016), but not in Northern Spanish. We suggest that dysregulation of glucose metabolism contributes to the development of AD and might be due in part to genetic variations in INS and PPARA and their interaction especially in Northern Europeans. PMID:22065208

Kölsch, Heike; Lehmann, Donald J; Ibrahim-Verbaas, Carla A; Combarros, Onofre; van Duijn, Cornelia M; Hammond, Naomi; Belbin, Olivia; Cortina-Borja, Mario; Lehmann, Michael G; Aulchenko, Yurii S; Schuur, Maaike; Breteler, Monique; Wilcock, Gordon K; Brown, Kristelle; Kehoe, Patrick G; Barber, Rachel; Coto, Eliecer; Alvarez, Victoria; Deloukas, Panos; Mateo, Ignacio; Maier, Wolfgang; Morgan, Kevin; Warden, Donald R; Smith, A David; Heun, Reinhard

2012-04-01

274

Discovery Learning Community  

NSDL National Science Digital Library

Discovery Communications (better known as The Discovery Channel and The Learning Channel) has announced the launch of a pilot Internet site designed to help teachers, students, and their educational partners devise innovative uses of Discovery programming. The Discovery Learning Community provides resources, relationships and collaborative tools to promote academic inquiry and knowledge building.

275

A new set of ESTs and cDNA clones from full-length and normalized libraries for gene discovery and functional characterization in citrus  

Microsoft Academic Search

BACKGROUND: Interpretation of ever-increasing raw sequence information generated by modern genome sequencing technologies faces multiple challenges, such as gene function analysis and genome annotation. Indeed, nearly 40% of genes in plants encode proteins of unknown function. Functional characterization of these genes is one of the main challenges in modern biology. In this regard, the availability of full-length cDNA clones may

M. Carmen Marques; Hugo Alonso-Cantabrana; Javier Forment; Raquel Arribas; Santiago Alamar; Vicente Conejero; Miguel A Perez-Amador

2009-01-01

276

Moments of Discovery: A Pulsar Discovery  

NSDL National Science Digital Library

This online exhibit from the American Institute of Physics contains the history of the discovery of the first optical pulsar in the Crab Nebula. It includes both a transcription of the conversation at the moment of the discovery and commentary by the astronomers who made the discovery and by Philip Morrison. MP3 files of the conversations, commentary, and ideas for use by teachers are included.

2008-02-15

277

In Pursuit of Interesting Patterns with Undirected Discovery of Exception Rules  

Microsoft Academic Search

This paper reports our progress on interesting pattern discovery in the discovery science project. We first introduce undirected\\u000a discovery of exception rules, in which a pattern represents a pair of an exception rule and its corresponding strong rule.\\u000a Then, we explain scheduled discovery, exception rule discovery guided by a meta-pattern, and data mining contests as our contribution\\u000a to the project.

Einoshin Suzuki

2002-01-01

278

Discovery of a Strongly-Interrelated Gene Network in Corals under Constant Darkness by Correlation Analysis after Wavelet Transform on Complex Network Model  

PubMed Central

Coral reefs occupy a relatively small portion of sea area, yet serve as a crucial source of biodiversity by establishing harmonious ecosystems with marine plants and animals. Previous researches mainly focused on screening several key genes induced by stress. Here we proposed a novel method—correlation analysis after wavelet transform of complex network model, to explore the effect of light on gene expression in the coral Acropora millepora based on microarray data. In this method, wavelet transform and the conception of complex network were adopted, and 50 key genes with large differences were finally captured, including both annotated genes and novel genes without accurate annotation. These results shed light on our understanding of coral's response toward light changes and the genome-wide interaction among genes under the control of biorhythm, and hence help us to better protect the coral reef ecosystems. Further studies are needed to explore how functional connections are related to structural connections, and how connectivity arises from the interactions within and between different systems. The method introduced in this study for analyzing microarray data will allow researchers to explore genome-wide interaction network with their own dataset and understand the relevant biological processes. PMID:24651851

Zhou, Xilong; Liu, Xuefeng; Zhang, Zhaobao; Wang, Xumin; Liu, Tao; Liu, Guiming

2014-01-01

279

How the serotonin story is being rewritten by new gene-based discoveries principally related to SLC6A4, the serotonin transporter gene, which functions to influence all cellular serotonin systems  

Microsoft Academic Search

Discovered and crystallized over sixty years ago, serotonin's important functions in the brain and body were identified over the ensuing years by neurochemical, physiological and pharmacological investigations. This 2008 M. Rapport Memorial Serotonin Review focuses on some of the most recent discoveries involving serotonin that are based on genetic methodologies. These include examples of the consequences that result from direct

Dennis L. Murphy; Meredith A. Fox; Kiara R. Timpano; Pablo R. Moya; Renee Ren-Patterson; Anne M. Andrews; Andrew Holmes; Klaus-Peter Lesch; Jens R. Wendland

2008-01-01

280

Analysis of expressed sequence tags from Actinidia: applications of a cross species EST database for gene discovery in the areas of flavor, health, color and ripening  

PubMed Central

Background Kiwifruit (Actinidia spp.) are a relatively new, but economically important crop grown in many different parts of the world. Commercial success is driven by the development of new cultivars with novel consumer traits including flavor, appearance, healthful components and convenience. To increase our understanding of the genetic diversity and gene-based control of these key traits in Actinidia, we have produced a collection of 132,577 expressed sequence tags (ESTs). Results The ESTs were derived mainly from four Actinidia species (A. chinensis, A. deliciosa, A. arguta and A. eriantha) and fell into 41,858 non redundant clusters (18,070 tentative consensus sequences and 23,788 EST singletons). Analysis of flavor and fragrance-related gene families (acyltransferases and carboxylesterases) and pathways (terpenoid biosynthesis) is presented in comparison with a chemical analysis of the compounds present in Actinidia including esters, acids, alcohols and terpenes. ESTs are identified for most genes in color pathways controlling chlorophyll degradation and carotenoid biosynthesis. In the health area, data are presented on the ESTs involved in ascorbic acid and quinic acid biosynthesis showing not only that genes for many of the steps in these pathways are represented in the database, but that genes encoding some critical steps are absent. In the convenience area, genes related to different stages of fruit softening are identified. Conclusion This large EST resource will allow researchers to undertake the tremendous challenge of understanding the molecular basis of genetic diversity in the Actinidia genus as well as provide an EST resource for comparative fruit genomics. The various bioinformatics analyses we have undertaken demonstrates the extent of coverage of ESTs for genes encoding different biochemical pathways in Actinidia. PMID:18655731

Crowhurst, Ross N; Gleave, Andrew P; MacRae, Elspeth A; Ampomah-Dwamena, Charles; Atkinson, Ross G; Beuning, Lesley L; Bulley, Sean M; Chagne, David; Marsh, Ken B; Matich, Adam J; Montefiori, Mirco; Newcomb, Richard D; Schaffer, Robert J; Usadel, Bjorn; Allan, Andrew C; Boldingh, Helen L; Bowen, Judith H; Davy, Marcus W; Eckloff, Rheinhart; Ferguson, A Ross; Fraser, Lena G; Gera, Emma; Hellens, Roger P; Janssen, Bart J; Klages, Karin; Lo, Kim R; MacDiarmid, Robin M; Nain, Bhawana; McNeilage, Mark A; Rassam, Maysoon; Richardson, Annette C; Rikkerink, Erik HA; Ross, Gavin S; Schroder, Roswitha; Snowden, Kimberley C; Souleyre, Edwige JF; Templeton, Matt D; Walton, Eric F; Wang, Daisy; Wang, Mindy Y; Wang, Yanming Y; Wood, Marion; Wu, Rongmei; Yauk, Yar-Khing; Laing, William A

2008-01-01

281

Discovery Mechanisms for the Sensor Web  

PubMed Central

This paper addresses the discovery of sensors within the OGC Sensor Web Enablement framework. Whereas services like the OGC Web Map Service or Web Coverage Service are already well supported through catalogue services, the field of sensor networks and the according discovery mechanisms is still a challenge. The focus within this article will be on the use of existing OGC Sensor Web components for realizing a discovery solution. After discussing the requirements for a Sensor Web discovery mechanism, an approach will be presented that was developed within the EU funded project “OSIRIS”. This solution offers mechanisms to search for sensors, exploit basic semantic relationships, harvest sensor metadata and integrate sensor discovery into already existing catalogues. PMID:22574038

Jirka, Simon; Broring, Arne; Stasch, Christoph

2009-01-01

282

NCI DTP Discovery Services  

Cancer.gov

Discovery Services Home Discovery Development Pathways Grants/Contracts Books/Publications Site Search Data Search What's New FAQs Repositories Synthetics, Natural Products, Radiolabeled Materials, Biologics Reference Standards and Reagents, Tumor Repository Animal

283

Discovery and Characterization of a Silent Gene Cluster that Produces Azaphilones from Aspergillus niger ATCC 1015 Reveal a Hydroxylation-Mediated Pyran-Ring Formation  

PubMed Central

SUMMARY Azaphilones are a class of fungal metabolites characterized by a highly oxygenated pyrano-quinone bicyclic core and exhibits a broad range of bioactivities. While widespread among various fungi, their biosynthesis has not been thoroughly elucidated. By activation of a silent (aza) gene cluster in Aspergillus niger ATCC 1015, we have discovered six new azaphilone compounds, azanigerones A-F (1, 3-7). Transcriptional analysis and deletion of a key polyketide synthase (PKS) gene further confirmed the involvement of the aza gene cluster. The biosynthetic pathway was shown to involve the convergent actions of a highly-reducing and a non-reducing PKSs. Most significantly, in vitro reaction of a key flavin-dependent monooxygenase encoded in the cluster with an early benzaldehyde intermediate revealed its roles in hydroxylation and pyran-ring formation to afford the characteristic bicylic core shared by azaphilones. PMID:22921072

Zabala, Angelica O.; Xu, Wei; Chooi, Yit-Heng; Tang, Yi

2012-01-01

284

Genes  

NSDL National Science Digital Library

Illustration of the placement of genes in a chromosome. A gene can be defined as a region of DNA that controls a hereditary characteristic. It usually corresponds to a sequence used in the production of a specific protein or RNA. A gene carries biological information in a form that must be copied and transmitted from each cell to all its progeny. This includes the entire functional unit: coding DNA sequences, non-coding regulatory DNA sequences, and introns. Genes can be as short as 1000 base pairs or as long as several hundred thousand base pairs. It can even be carried by more than one chromosome. The estimate for the number of genes in humans has decreased as our knowledge has increased. As of 2001, humans are thought to have between 30,000 and 40,000 genes.

Excellence, Access

2005-03-12

285

Allele discovery of ten candidate drought-response genes in Austrian oak using a systematically informatics approach based on 454 amplicon sequencing  

PubMed Central

Background Rise of temperatures and shortening of available water as result of predicted climate change will impose significant pressure on long-lived forest tree species. Discovering allelic variation present in drought related genes of two Austrian oak species can be the key to understand mechanisms of natural selection and provide forestry with key tools to cope with future challenges. Results In the present study we have used Roche 454 sequencing and developed a bioinformatic pipeline to process multiplexed tagged amplicons in order to identify single nucleotide polymorphisms and allelic sequences of ten candidate genes related to drought/osmotic stress from sessile oak (Quercus robur) and sessile oak (Q. petraea) individuals. Out of these, eight genes of 336 oak individuals growing in Austria have been detected with a total number of 158 polymorphic sites. Allele numbers ranged from ten to 52 with observed heterozygosity ranging from 0.115 to 0.640. All loci deviated from Hardy-Weinberg equilibrium and linkage disequilibrium was found among six combinations of loci. Conclusions We have characterized 183 alleles of drought related genes from oak species and detected first evidences of natural selection. Beside the potential for marker development, we have created an expandable bioinformatic pipeline for the analysis of next generation sequencing data. PMID:22472016

2012-01-01

286

VeloceGenomics: An Accelerated in Vivo Drug Discovery Approach to Rapidly Predict the Biologic, Drug-Like Activity of Compounds, Proteins, or Genes  

Microsoft Academic Search

:Purpose. The aim of this study is to test the predictive power of in vivo multiorgan RNA expression profiling in identifying the biologic activity of molecules. Methods. Animals were treated with compound A or B. At the end of the treatment period, in vivo multiorgan microarray-based gene expression data were collected. Investigators masked to the identity of the compounds analyzed

Ruben Papoian; Andreas Scherer; Muriel Saulnier; Frank Staedtler; André Cordier; Francois Legay; Gerard Maurer; Joerg Staeheli; Jacky Vonderscher; Salah-Dine Chibout

2005-01-01

287

Transcriptome sequencing and annotation of the microalgae Dunaliella tertiolecta: Pathway description and gene discovery for production of next-generation biofuels  

PubMed Central

Background Biodiesel or ethanol derived from lipids or starch produced by microalgae may overcome many of the sustainability challenges previously ascribed to petroleum-based fuels and first generation plant-based biofuels. The paucity of microalgae genome sequences, however, limits gene-based biofuel feedstock optimization studies. Here we describe the sequencing and de novo transcriptome assembly for the non-model microalgae species, Dunaliella tertiolecta, and identify pathways and genes of importance related to biofuel production. Results Next generation DNA pyrosequencing technology applied to D. tertiolecta transcripts produced 1,363,336 high quality reads with an average length of 400 bases. Following quality and size trimming, ~ 45% of the high quality reads were assembled into 33,307 isotigs with a 31-fold coverage and 376,482 singletons. Assembled sequences and singletons were subjected to BLAST similarity searches and annotated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) orthology (KO) identifiers. These analyses identified the majority of lipid and starch biosynthesis and catabolism pathways in D. tertiolecta. Conclusions The construction of metabolic pathways involved in the biosynthesis and catabolism of fatty acids, triacylglycrols, and starch in D. tertiolecta as well as the assembled transcriptome provide a foundation for the molecular genetics and functional genomics required to direct metabolic engineering efforts that seek to enhance the quantity and character of microalgae-based biofuel feedstock. PMID:21401935

2011-01-01

288

Next-generation pyrosequencing of gonad transcriptomes in the polyploid lake sturgeon (Acipenser fulvescens): the relative merits of normalization and rarefaction in gene discovery  

Microsoft Academic Search

BACKGROUND: Next-generation sequencing technologies have been applied most often to model organisms or species closely related to a model. However, these methods have the potential to be valuable in many wild organisms, including those of conservation concern. We used Roche 454 pyrosequencing to characterize gene expression in polyploid lake sturgeon (Acipenser fulvescens) gonads. RESULTS: Titration runs on a Roche 454

Matthew C Hale; Cory R McCormick; James R Jackson; J Andrew DeWoody

2009-01-01

289

Detection and discovery of crustacean parasites in blue crabs (Callinectes sapidus) by using 18S rRNA gene-targeted denaturing high-performance liquid chromatography.  

PubMed

Recently, we described a novel denaturing high-performance liquid chromatography (DHPLC) approach useful for initial detection and identification of crustacean parasites. Because this approach utilizes general primers targeted to conserved regions of the 18S rRNA gene, a priori genetic sequence information on eukaryotic parasites is not required. This distinction provides a significant advantage over specifically targeted PCR assays that do not allow for the detection of unknown or unsuspected parasites. However, initial field evaluations of the DHPLC assay suggested that because of PCR-biased amplification of dominant host genes it was not possible to detect relatively rare parasite genes in infected crab tissue. Here, we describe the use of a peptide nucleic acid (PNA) PCR hybridization blocking probe in association with DHPLC (PNA-PCR DHPLC) to overcome inherent PCR bias associated with amplification of rare target genes by use of generic primers. This approach was utilized to detect infection of blue crabs (Callinectes sapidus) by the parasitic dinoflagellate Hematodinium sp. Evaluation of 76 crabs caught in Wassaw Sound, GA, indicated a 97% correspondence between detection of the parasite by use of a specific PCR diagnostic assay and that by use of PNA-PCR DHPLC. During these studies, we discovered one crab with an association with a previously undescribed protist symbiont. Phylogenetic analysis of the amplified symbiont 18S rRNA gene indicated that it is most closely related to the free-living kinetoplastid parasite Procryptobia sorokini. To our knowledge, this is the first report of this parasite group in a decapod crab and of this organism exhibiting a presumably parasitic life history. PMID:18502913

Troedsson, Christofer; Lee, Richard F; Walters, Tina; Stokes, Vivica; Brinkley, Karrie; Naegele, Verena; Frischer, Marc E

2008-07-01

290

Detection and Discovery of Crustacean Parasites in Blue Crabs (Callinectes sapidus) by Using 18S rRNA Gene-Targeted Denaturing High-Performance Liquid Chromatography? †  

PubMed Central

Recently, we described a novel denaturing high-performance liquid chromatography (DHPLC) approach useful for initial detection and identification of crustacean parasites. Because this approach utilizes general primers targeted to conserved regions of the 18S rRNA gene, a priori genetic sequence information on eukaryotic parasites is not required. This distinction provides a significant advantage over specifically targeted PCR assays that do not allow for the detection of unknown or unsuspected parasites. However, initial field evaluations of the DHPLC assay suggested that because of PCR-biased amplification of dominant host genes it was not possible to detect relatively rare parasite genes in infected crab tissue. Here, we describe the use of a peptide nucleic acid (PNA) PCR hybridization blocking probe in association with DHPLC (PNA-PCR DHPLC) to overcome inherent PCR bias associated with amplification of rare target genes by use of generic primers. This approach was utilized to detect infection of blue crabs (Callinectes sapidus) by the parasitic dinoflagellate Hematodinium sp. Evaluation of 76 crabs caught in Wassaw Sound, GA, indicated a 97% correspondence between detection of the parasite by use of a specific PCR diagnostic assay and that by use of PNA-PCR DHPLC. During these studies, we discovered one crab with an association with a previously undescribed protist symbiont. Phylogenetic analysis of the amplified symbiont 18S rRNA gene indicated that it is most closely related to the free-living kinetoplastid parasite Procryptobia sorokini. To our knowledge, this is the first report of this parasite group in a decapod crab and of this organism exhibiting a presumably parasitic life history. PMID:18502913

Troedsson, Christofer; Lee, Richard F.; Walters, Tina; Stokes, Vivica; Brinkley, Karrie; Naegele, Verena; Frischer, Marc E.

2008-01-01

291

Human Lung Project: Evaluating Variance of Gene Expression in the Human Lung  

PubMed Central

Nondiseased tissue is an important reference for microarray studies of pulmonary disease. We obtained 23 single lungs from multiorgan donors at time of procurement. Donors varied in age, sex, smoking history, and ethnicity. Lungs were dissected into upper and lower lobe peripheral sections for RNA extraction. Microarray analysis was performed using Affymetrix Hu-133 Plus 2.0 arrays. We observed that the relative variability of gene expression increased rapidly from technical (lowest), to regional, to population (highest). In addition, age and sex have measurable effects on gene expression. Gene expression variability is heterogeneously distributed among biologic categories. We conclude that gene expression variability is greater between individuals than within individuals and that population variability is the most important factor in the study design of microarray experiments of the human lung. Classes of genes with high population variability are biologically important and provide a novel perspective into lung physiology and pathobiology. Our study represents the first comprehensive analysis of nondiseased lung tissue. The generation of this robust dataset has important implications for the design and implementation of future comparative expression analysis with pulmonary disease states. PMID:16498083

Gruber, Michael P.; Coldren, Christopher D.; Woolum, Malcolm D.; Cosgrove, Gregory P.; Zeng, Chan; Baron, Anna E.; Moore, Mark D.; Cool, Carlyne D.; Worthen, G. Scott; Brown, Kevin K.; Geraci, Mark W.

2006-01-01

292

Environmental Regulation of Plant Gene Expression: An Rt-qPCR Laboratory Project for an Upper-Level Undergraduate Biochemistry or Molecular Biology Course  

ERIC Educational Resources Information Center

We present a novel laboratory project employing "real-time" RT-qPCR to measure the effect of environment on the expression of the "FLOWERING LOCUS C" gene, a key regulator of floral timing in "Arabidopsis thaliana" plants. The project requires four 3-hr laboratory sessions and is aimed at upper-level undergraduate…

Eickelberg, Garrett J.; Fisher, Alison J.

2013-01-01

293

Gene hunting in autoinflammation  

PubMed Central

Steady progress in our understanding of the genetic basis of autoinflammatory diseases has been made over the past 16 years. Since the discovery of the familial Mediterranean fever gene MEFV (also known as marenostrin) in 1997, 18 other genes responsible for monogenic autoinflammatory diseases have been identified to date. The discovery of these genes was made through the utilisation of many genetic mapping techniques, including next generation sequencing platforms. This review article clearly describes the gene hunting approaches, methods of data analysis and the technological platforms used, which has relevance to all those working within the field of gene discovery for Mendelian disorders. PMID:24070009

2013-01-01

294

The extragalactic distance scale Key Project. III. The discovery of Cepheids and a new distance to M101 using the {ital Hubble} {ital Space} {ital Telescope}  

SciTech Connect

We report on the discovery of 29 Cepheid variables in the galaxy M101 using the original Wide Field Camera (WFC) and the new Wide Field and Planetary Camera 2 (WFPC2) on the {ital Hubble} {ital Space} {ital Telescope}. We observed a field in M101 at 17 independent epochs in {ital V} (F555W), five epochs in {ital I} (F785LP/F814W), and one epoch in {ital B} (F439W), with a time interval baseline of 381 days. We have found Cepheids with periods ranging from 10 to 60 days. The data have been calibrated using WFPC2 observations with zero points derived from {omega} Cen, Pal 4, and NGC 2419 observations. This calibration has been verified by using the Medium Deep Survey (MDS) WFC photometric zero points, and ground-based secondary standards in {ital V} and {ital I}. The {ital V} calibrations agree to {plus_minus}0.06 mag, and the {ital I} calibrations agree to {plus_minus}0.04 mag. We have constructed {ital V} and {ital I} period-luminosity (PL) relations and have derived apparent distance moduli based on a distance modulus for the Large Magellanic Cloud (LMC) of 18.50 mag and a reddening of {ital E}({ital B}{minus}{ital V})=0.10 mag to the LMC Cepheids. Period-residual minimization was used to minimize the effects of Malmquist bias on the period-luminosity relation fitting process. Using a Galactic extinction law and the apparent {ital V} and {ital I} distance moduli, we have found a mean reddening for the M101 sample of {ital E}({ital B}{minus}{ital V})=0.03 mag and a true distance modulus to M101 of 29.34{plus_minus}0.17 mag, corresponding to a distance of 7.4{plus_minus}0.6 Mpc. The sources of error have been rigorously tracked through an error budget; systematic and random errors contribute roughly equally to the quoted error. The mean gas-phase metal abundances in the LMC and in the M101 outer field are similar so we expect metallicity effects to be minimal. (Abstract Truncated)

Kelson, D.D.; Illingworth, G.D. [UCO/Lick Observatory, University of California, Santa Cruz, California 95064 (United States)] [UCO/Lick Observatory, University of California, Santa Cruz, California 95064 (United States); Freedman, W.F. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, California 91101 (United States)] [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, California 91101 (United States); Graham, J.A. [Department of Terrestrial Magnetism, Carnegie Institution of Washington, 5241 Broad Branch Road NW, Washington, District of Columbia 20015 (United States)] [Department of Terrestrial Magnetism, Carnegie Institution of Washington, 5241 Broad Branch Road NW, Washington, District of Columbia 20015 (United States); Hill, R. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, California 91101 (United States)] [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, California 91101 (United States); Madore, B.F. [NASA/IPAC Extragalactic Database, Infrared Processing and Analysis Center, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California 91125 (United States)] [NASA/IPAC Extragalactic Database, Infrared Processing and Analysis Center, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California 91125 (United States); Saha, A. [Space Telescope Institute, Homewood Campus, Baltimore, Maryland 21218 (United States)] [Space Telescope Institute, Homewood Campus, Baltimore, Maryland 21218 (United States); Stetson, P.B. [Dominion Astrophysical Observatory, National Research Council, 5071 West Saanich Road, Victoria, BC, V8X 4M6 (CANADA)] [Dominion Astrophysical Observatory, National Research Council, 5071 West Saanich Road, Victoria, BC, V8X 4M6 (CANADA); Kennicutt, R.C. Jr. [Steward Observatory, University of Arizona, Tucson, Arizona 85721 (United States)] [Steward Observatory, University of Arizona, Tucson, Arizona 85721 (United States); Mould, J.R. [Mt. Stromlo and Siding Springs Observatories, Private Bag, Weston Creek Post Office ACT 2611 (Australia)] [Mt. Stromlo and Siding Springs Observatories, Private Bag, Weston Creek Post Office ACT 2611 (Australia); Hughes, S.M. [Royal Greenwich Observatory, Madingley Road, Cambridge, (United Kingdom) CB3 0EZ] [Royal Greenwich Observatory, Madingley Road, Cambridge, (United Kingdom) CB3 0EZ; Ferrarese, L. [Space Telescope Institute, Homewood Campus, Baltimore, Maryland 21218 (United States)] [Space Telescope Institute, Homewood Campus, Baltimore, Maryland 21218 (United States); [Department of Physics and Astronomy, Bloomberg 501, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218 (United States); Phelps, R. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, California 91101 (United States)] [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, California 91101 (United States); Turner, A. [Steward Observatory, University of Arizona, Tucson, Arizona 85721 (United States)] [Steward Observatory, University of Arizona, Tucson, Arizona 85721 (United States); Cook, K.H. [Lawrence Livermore National Laboratory, Mississippi L-401, P.O. Box 808, Livermore, California 94550 (United States)] [Lawrence Livermore National Laboratory, Mississippi L-401, P.O. Box 808, Livermore, California 94550 (United States); Ford, H. [Space Telescope Institute, Homewood Campus, Baltimore, Maryland 21218 (United States)] [Space Telescope Institute, Homewood Campus, Baltimore, Maryland 21218 (United States)

1996-05-01

295

Antarctic macrozooplankton of the southwest Atlantic sector and Bellingshausen Sea: Baseline historical distributions ( Discovery Investigations, 1928-1935) related to temperature and food, with projections for subsequent ocean warming  

NASA Astrophysics Data System (ADS)

Since the Discovery Investigations of the 1920s and 1930s, seawater temperatures have increased in the Atlantic sector by ˜1 °C; greater than the global mean rise. The aims of this paper were first to rescue the Discovery macrozooplankton data, second to provide quantitative "baseline" distribution maps, relating these to indices of temperature and food. Our third aim was to use the relationships we derived between abundance and temperature to project the potential affect of a 1 °C warming on the Discovery era distribution patterns. Based on the 1 m ringnet data retrieved from 615 stations (Nov-March), four taxa comprised >90% of the Antarctic macrozooplankton abundance: Rhincalanus gigas, Thysanoessa spp., Euphausia superba, and Chaetognaths. Most of the taxa, especially the more abundant ones, were warm water species penetrating into Antarctica and thus total macrozooplankton abundance decreased about 100-fold from 50°S to 70°S. While temperature correlated best with distribution at this large scale, food availability (proxied by a present-day satellite-based Chlorophyll a climatology) had a secondary effect, with the major euphausiids Euphausia superba and Thysanoessa spp. concentrated in high chl a areas. A modelled uniform 1 °C temperature rise produced a poleward shift for all taxa, but the Antarctic continent blocked this re-adjustment for the high latitude species, constricting their predicted range. More widespread polar/sub-polar species were predicted to increase their penetration into Antarctica by 4-12° in latitude, whereas the poleward shift in potential range of sub-Antarctic taxa were limited by the steep temperature gradient across the Antarctic Polar Front (APF). However, within the Scotia Sea the relatively warm temperatures of the northern Antarctic Zone, abundant food due to iron fertilisation and intense eddy activity provide a "gateway" for northern species to penetrate south of the APF. Our model predictions, based on measured distributional ranges and observed temperature increases, provide a yardstick with which to compare modern day data compilations and assess the potential effects of future temperature increases.

Mackey, A. P.; Atkinson, A.; Hill, S. L.; Ward, P.; Cunningham, N. J.; Johnston, N. M.; Murphy, E. J.

2012-01-01

296

Insights into Hepatopancreatic Functions for Nutrition Metabolism and Ovarian Development in the Crab Portunus trituberculatus: Gene Discovery in the Comparative Transcriptome of Different Hepatopancreas Stages  

PubMed Central

The crustacean hepatopancreas has different functions including absorption, storage of nutrients and vitellogenesis during growth, and ovarian development. However, genetic information on the biological functions of the crustacean hepatopancreas during such processes is limited. The swimming crab, Portunus trituberculatus, is a commercially important species for both aquaculture and fisheries in the Asia-Pacific region. This study compared the transcriptome in the hepatopancreas of female P. trituberculatus during the growth and ovarian maturation stages by 454 high-throughput pyrosequencing and bioinformatics. The goal was to discover genes in the hepatopancreas involved in food digestion, nutrition metabolism and ovarian development, and to identify patterns of gene expression during growth and ovarian maturation. Our transcriptome produced 303,450 reads with an average length of 351 bp, and the high quality reads were assembled into 21,635 contigs and 31,844 singlets. Based on BLASTP searches of the deduced protein sequences, there were 7,762 contigs and 4,098 singlets with functional annotation. Further analysis revealed 33,427 unigenes with ORFs, including 17,388 contigs and 16,039 singlets in the hepatopancreas, while only 7,954 unigenes (5,691 contigs and 2,263 singlets) with the predicted protein sequences were annotated with biological functions. The deduced protein sequences were assigned to 3,734 GO terms, 25 COG categories and 294 specific pathways. Furthermore, there were 14, 534, and 22 identified unigenes involved in food digestion, nutrition metabolism and ovarian development, respectively. 212 differentially expressed genes (DEGs) were found between the growth and endogenous stage of the hepatopancreas, while there were 382 DEGs between the endogenous and exogenous stage hepatopancreas. Our results not only enhance the understanding of crustacean hepatopancreatic functions during growth and ovarian development, but also represent a basis for further research on new genes and functional genomics of P. trituberculatus or closely related species. PMID:24454766

Liu, Zhijun; Zheng, Huajun; Cheng, Yongxu

2014-01-01

297

Insights into hepatopancreatic functions for nutrition metabolism and ovarian development in the crab Portunus trituberculatus: gene discovery in the comparative transcriptome of different hepatopancreas stages.  

PubMed

The crustacean hepatopancreas has different functions including absorption, storage of nutrients and vitellogenesis during growth, and ovarian development. However, genetic information on the biological functions of the crustacean hepatopancreas during such processes is limited. The swimming crab, Portunus trituberculatus, is a commercially important species for both aquaculture and fisheries in the Asia-Pacific region. This study compared the transcriptome in the hepatopancreas of female P. trituberculatus during the growth and ovarian maturation stages by 454 high-throughput pyrosequencing and bioinformatics. The goal was to discover genes in the hepatopancreas involved in food digestion, nutrition metabolism and ovarian development, and to identify patterns of gene expression during growth and ovarian maturation. Our transcriptome produced 303,450 reads with an average length of 351 bp, and the high quality reads were assembled into 21,635 contigs and 31,844 singlets. Based on BLASTP searches of the deduced protein sequences, there were 7,762 contigs and 4,098 singlets with functional annotation. Further analysis revealed 33,427 unigenes with ORFs, including 17,388 contigs and 16,039 singlets in the hepatopancreas, while only 7,954 unigenes (5,691 contigs and 2,263 singlets) with the predicted protein sequences were annotated with biological functions. The deduced protein sequences were assigned to 3,734 GO terms, 25 COG categories and 294 specific pathways. Furthermore, there were 14, 534, and 22 identified unigenes involved in food digestion, nutrition metabolism and ovarian development, respectively. 212 differentially expressed genes (DEGs) were found between the growth and endogenous stage of the hepatopancreas, while there were 382 DEGs between the endogenous and exogenous stage hepatopancreas. Our results not only enhance the understanding of crustacean hepatopancreatic functions during growth and ovarian development, but also represent a basis for further research on new genes and functional genomics of P. trituberculatus or closely related species. PMID:24454766

Wang, Wei; Wu, Xugan; Liu, Zhijun; Zheng, Huajun; Cheng, Yongxu

2014-01-01

298

A roadmap for natural product discovery based on large-scale genomics and metabolomics.  

PubMed

Actinobacteria encode a wealth of natural product biosynthetic gene clusters, whose systematic study is complicated by numerous repetitive motifs. By combining several metrics, we developed a method for the global classification of these gene clusters into families (GCFs) and analyzed the biosynthetic capacity of Actinobacteria in 830 genome sequences, including 344 obtained for this project. The GCF network, comprising 11,422 gene clusters grouped into 4,122 GCFs, was validated in hundreds of strains by correlating confident mass spectrometric detection of known small molecules with the presence or absence of their established biosynthetic gene clusters. The method also linked previously unassigned GCFs to known natural products, an approach that will enable de novo, bioassay-free discovery of new natural products using large data sets. Extrapolation from the 830-genome data set reveals that Actinobacteria encode hundreds of thousands of future drug leads, and the strong correlation between phylogeny and GCFs frames a roadmap to efficiently access them. PMID:25262415

Doroghazi, James R; Albright, Jessica C; Goering, Anthony W; Ju, Kou-San; Haines, Robert R; Tchalukov, Konstantin A; Labeda, David P; Kelleher, Neil L; Metcalf, William W

2014-11-01

299

DIRECTING POTENTIAL ANTI-XYLELLA GENE PRODUCTS TO THE XYLEM OF TRANSGENIC GRAPEVINES Project Leaders  

Microsoft Academic Search

The purpose of this research was to transform Vitis vinifera cultivars with the pear polygalacturonase inhibiting protein (PGIP) gene in order to analyze its effect in developing resistance to PD in transgenic plants. A second goal was the transformation of grapevine with several green fluorescence protein (GFP) constructs carrying sequences expected to enhance secretion from the cell to evaluate the

Carole Meredith; Abhaya Dandekar; Bruce Kirkpatrick; John Labavitch

300

Studying Human Disease Genes in "Caenorhabditis Elegans": A Molecular Genetics Laboratory Project  

ERIC Educational Resources Information Center

Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether "Caenorhabditis elegans" can be a useful model system for studying genes

Cox-Paulson, Elisabeth A.; Grana, Theresa M.; Harris, Michelle A.; Batzli, Janet M.

2012-01-01

301

The Alabama Drug Discovery Alliance: A Collaborative Partnership to Facilitate Academic Drug Discovery  

PubMed Central

The Alabama Drug Discovery Alliance is a collaboration between the University of Alabama at Birmingham and Southern Research Institute that aims to support the discovery and development of therapeutic molecules that address an unmet medical need. The alliance builds on the expertise present at both institutions and has the dedicated commitment of their respective technology transfer and intellectual property offices to guide any commercial opportunities that may arise from the supported efforts. Although most projects involve high throughput screening, projects at any stage in the drug discovery and development pathway are eligible for support. Irrespective of the target and stage of any project, well-functioning interdisciplinary teams are crucial to a project’s progress. These teams consist of investigators with a wide variety of expertise from both institutions to contribute to the program’s success. PMID:21448756

Everts, Maaike; Knight, W. Blaine; Harris, David R.; Secrist, John A.; Whitley, Richard J.

2011-01-01

302

Discovery of Western European R1b1a2 Y chromosome variants in 1000 genomes project data: an online community approach.  

PubMed

The authors have used an online community approach, and tools that were readily available via the Internet, to discover genealogically and therefore phylogenetically relevant Y-chromosome polymorphisms within core haplogroup R1b1a2-L11/S127 (rs9786076). Presented here is the analysis of 135 unrelated L11 derived samples from the 1000 Genomes Project. We were able to discover new variants and build a much more complex phylogenetic relationship for L11 sub-clades. Many of the variants were further validated using PCR amplification and Sanger sequencing. The identification of these new variants will help further the understanding of population history including patrilineal migrations in Western and Central Europe where R1b1a2 is the most frequent haplogroup. The fine-grained phylogenetic tree we present here will also help to refine historical genetic dating studies. Our findings demonstrate the power of citizen science for analysis of whole genome sequence data. PMID:22911832

Rocca, Richard A; Magoon, Gregory; Reynolds, David F; Krahn, Thomas; Tilroe, Vincent O; Op den Velde Boots, Peter M; Grierson, Andrew J

2012-01-01

303

Gene-centric view on the human proteome project: the example of the Russian roadmap for chromosome 18.  

PubMed

During the 2010 Human Proteome Organization Congress in Sydney, a gene-centric approach emerged as a feasible and tractable scaffold for assemblage of the Human Proteome Project. Bringing the gene-centric principle into practice, a roadmap for the 18th chromosome was drafted, postulating the limited sensitivity of analytical methods, as a serious bottleneck in proteomics. In the context of the sensitivity problem, we refer to the "copy number of protein molecules" as a measurable assessment of protein abundance. The roadmap is focused on the development of technology to attain the low- and ultralow -"copied" portion of the proteome. Roadmap merges the genomic, transcriptomic and proteomic levels to identify the majority of 285 proteins from 18th chromosome - master proteins. Master protein is the primary translation of the coding sequence and resembling at least one of the known isoforms, coded by the gene. The executive phase of the roadmap includes the expansion of the study of the master proteins with alternate splicing, single amino acid polymorphisms (SAPs) and post-translational modifications. In implementing the roadmap, Russian scientists are expecting to establish proteomic technologies for integrating MS and atomic force microscopy (AFM). These technologies are anticipated to unlock the value of new biomarkers at a detection limit of 10(-18) M, i.e. 1 protein copy per 1 ?L of plasma. The roadmap plan is posted at www.proteome.ru/en/roadmap/ and a forum for discussion of the document is supported. PMID:21563312

Archakov, Alexander; Aseev, Alexander; Bykov, Victor; Grigoriev, Anatoly; Govorun, Vadim; Ivanov, Vadim; Khlunov, Alexander; Lisitsa, Andrey; Mazurenko, Sergey; Makarov, Alexander A; Ponomarenko, Elena; Sagdeev, Renad; Skryabin, Konstantin

2011-05-01

304

The Human Genome Project and the breast-ovarian cancer gene  

Microsoft Academic Search

The Human Genome Project is a large scale international effort to create physical, genetic, and nucleotide sequence maps of the entire human genome. This initiative, which was begun in 1990, is expected to achieve its goal of sequencing the entire human genome by the year 2005. Undoubtedly, this massive resource will substantially enhance our ability to diagnose predisposition to disease

Holly H. Gallion

1996-01-01

305

N-CARBAMYLGLUTAMATE ENHANCEMENT OF UREAGENESIS LEADS TO DISCOVERY OF A NOVEL DELETERIOUS MUTATION IN A NEWLY DEFINED ENHANCER OF THE NAGS GENE AND TO EFFECTIVE THERAPY  

PubMed Central

NAGS catalyzes the conversion of glutamate and acetyl-CoA to N-acetylglutamate (NAG) the essential allosteric activator of carbamyl phosphate synthetase I, the first urea cycle enzyme in mammals. A 17-year-old female with recurrent hyperammonemia attacks, the cause of which remained undiagnosed for 8 years in spite of multiple molecular and biochemical investigations, showed markedly enhanced ureagenesis (measured by isotope incorporation) in response to N-carbamylglutamate (NCG). This led to sequencing of the regulatory regions of the NAG synthase (NAGS) gene and identification of a deleterious single-base substitution in the upstream enhancer. The homozygous mutation (-3063C>A), affecting a highly conserved nucleotide within the Hepatic Nuclear Factor 1 (HNF-1) binding site, was not found in SNP databases and in a screen of 1086 alleles from a diverse population. Functional assays demonstrated that this mutation decreases transcription and binding of HNF-1 to the NAGS gene, while a consensus HNF-1 binding sequence enhances binding to HNF-1 and increases transcription. Oral daily NCG therapy appears to have restored ureagenesis in this patient, normalizing her biochemical markers, and allowing discontinuation of alternate pathway therapy and normalization of her diet with no recurrence of hyperammonemia. PMID:21681857

Heibel, Sandra K.; Mew, Nicholas Ah; Caldovic, Ljubica; Daikhin, Yevgeny; Yudkoff, Marc; Tuchman, Mendel

2014-01-01

306

STS-92 Discovery Launch  

NASA Technical Reports Server (NTRS)

Viewed from across the waters of Banana Creek, clouds of smoke and steam are illuminated by the flames from Space Shuttle Discovery'''s perfect on-time launch at 7:17 p.m. EDT. Discovery carries a crew of seven on a construction flight to the International Space Station. Discovery also carries a payload that includes the Integrated Truss Structure Z-1, first of 10 trusses that will form the backbone of the Space Station, and the third Pressurized Mating Adapter that will provide a Shuttle docking port for solar array installation on the sixth Station flight and Lab installation on the seventh Station flight. Discovery'''s landing is expected Oct. 22 at 2:10 p.m. EDT.

2000-01-01

307

Transcriptome Analysis of Androgenic Gland for Discovery of Novel Genes from the Oriental River Prawn, Macrobrachium nipponense, Using Illumina Hiseq 2000  

PubMed Central

Background The oriental river prawn, Macrobrachium nipponense, is an important aquaculture species in China, even in whole of Asia. The androgenic gland produces hormones that play crucial roles in sexual differentiation to maleness. This study is the first de novo M. nipponense transcriptome analysis using cDNA prepared from mRNA isolated from the androgenic gland. Illumina/Solexa was used for sequencing. Methodology and Principal Finding The total volume of RNA sample was more than 5 ug. We generated 70,853,361 high quality reads after eliminating adapter sequences and filtering out low-quality reads. A total of 78,408 isosequences were obtained by clustering and assembly of the clean reads, producing 57,619 non-redundant transcripts with an average length of 1244.19 bp. In total 70,702 isosequences were matched to the Nr database, additional analyses were performed by GO (33,203), KEGG (17,868), and COG analyses (13,817), identifying the potential genes and their functions. A total of 47 sex-determination related gene families were identified from the M. nipponense androgenic gland transcriptome based on the functional annotation of non-redundant transcripts and comparisons with the published literature. Furthermore, a total of 40 candidate novel genes were found, that may contribute to sex-determination based on their extremely high expression levels in the androgenic compared to other sex glands,. Further, 437 SSRs and 65,535 high-confidence SNPs were identified in this EST dataset from which 14 EST-SSR markers have been isolated. Conclusion Our study provides new sequence information for M. nipponense, which will be the basis for further genetic studies on decapods crustaceans. More importantly, this study dramatically improves understanding of sex-determination mechanisms, and advances sex-determination research in all crustacean species. The huge number of potential SSR and SNP markers isolated from the transcriptome may shed the lights on research in many fields, including the evolution and molecular ecology of Macrobrachium species. PMID:24204682

Jin, Shubo; Fu, Hongtuo; Zhou, Qiao; Sun, Shengming; Jiang, Sufei; Xiong, Yiwei; Gong, Yongsheng; Qiao, Hui; Zhang, Wenyi

2013-01-01

308

Cross-repository Information Discovery in the Earth Sciences Adila Krisnadhia  

E-print Network

Cross-repository Information Discovery in the Earth Sciences Adila Krisnadhia , Robert Arkob, discovery and management across the geosciences. EARTHCUBE Conceptual modeling, Information Integration Project An EarthCube building block focused on ocean science knowledge infrastructure. Starts with 6

Hitzler, Pascal

309

A transcriptomic analysis of striped catfish (Pangasianodon hypophthalmus) in response to salinity adaptation: De novo assembly, gene annotation and marker discovery.  

PubMed

The striped catfish (Pangasianodon hypophthalmus) culture industry in the Mekong Delta in Vietnam has developed rapidly over the past decade. The culture industry now however, faces some significant challenges, especially related to climate change impacts notably from predicted extensive saltwater intrusion into many low topographical coastal provinces across the Mekong Delta. This problem highlights a need for development of culture stocks that can tolerate more saline culture environments as a response to expansion of saline water-intruded land. While a traditional artificial selection program can potentially address this need, understanding the genomic basis of salinity tolerance can assist development of more productive culture lines. The current study applied a transcriptomic approach using Ion PGM technology to generate expressed sequence tag (EST) resources from the intestine and swim bladder from striped catfish reared at a salinity level of 9ppt which showed best growth performance. Total sequence data generated was 467.8Mbp, consisting of 4,116,424 reads with an average length of 112bp. De novo assembly was employed that generated 51,188 contigs, and allowed identification of 16,116 putative genes based on the GenBank non-redundant database. GO annotation, KEGG pathway mapping, and functional annotation of the EST sequences recovered with a wide diversity of biological functions and processes. In addition, more than 11,600 simple sequence repeats were also detected. This is the first comprehensive analysis of a striped catfish transcriptome, and provides a valuable genomic resource for future selective breeding programs and functional or evolutionary studies of genes that influence salinity tolerance in this important culture species. PMID:24841517

Thanh, Nguyen Minh; Jung, Hyungtaek; Lyons, Russell E; Chand, Vincent; Tuan, Nguyen Viet; Thu, Vo Thi Minh; Mather, Peter

2014-06-01

310

Gene sequencing project finds family of drugs with promise for treating childhood tumor  

Cancer.gov

Drugs that enhance a process called oxidative stress were found to kill rhabdomyosarcoma tumor cells growing in the laboratory and possibly bolstered the effectiveness of chemotherapy against this aggressive tumor of muscle and other soft tissue. The findings are the latest from the St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project and appear in the December 9 edition of the scientific journal Cancer Cell.

311

Discovery of Ideas and Ideas about Discovery Casper Hulshof  

E-print Network

Discovery of Ideas and Ideas about Discovery Casper Hulshof 2001 Ph.D. thesis University of Twente Also available in print: www.tup.utwente.nl/uk/catalogue/educational/discovery Tw e nte Unive rsity Press #12;Casper Hulshof Discovery of Ideas and Ideas about Discovery #12;Publisher: Twente University

Paris-Sud XI, Université de

312

Discovery of a new gene pool and a high genetic diversity of the chestnut blight fungus Cryphonectria parasitica in Caucasian Georgia.  

PubMed

In this study, we investigated the population genetic structure and possible origins of the plant pathogen Cryphonectria parasitica in Caucasian Georgia, a region within the centre of origin of the host species Castanea sativa. A total of 427 C. parasitica isolates from nine populations were genotyped at 10 microsatellite loci. A high genetic diversity was detected, but the overall Georgian population was dominated by three haplotypes which were present in most individual populations. Two of them have not been previously found in Europe. Bayesian clustering analysis and principal component analysis could not identify their source population, neither in Asia nor in North America. On the other hand, one haplotype is frequent in Central Europe and probably naturally invaded Caucasian Georgia from neighbouring Turkey. Seventy-three haplotypes were unique to specific populations, and 66 of them were represented by a single isolate. Allele patterns suggest that most of these haplotypes emerged locally through sexual recombination between haplotypes of the Georgian and the central European gene pool. Due to the high incidence of haplotypes not otherwise present in Europe, Caucasian Georgia represents an additional source of diversity for the European C. parasitica population. PMID:23994123

Prospero, S; Lutz, A; Tavadze, B; Supatashvili, A; Rigling, D

2013-12-01

313

[My accidental discovery].  

PubMed

We wonder what we should do in medical care besides daily routine work as a laboratory technician. I made a discovery in my routine laboratory work, which gave me a theme for my research. This led to me successfully completing a number of scientific research projects, and these experiences have enabled me to be able to give advice on appropriate treatments for infectious diseases in medical care. It was March 1999 when I identified Escherichia coli (E. coli) in an intra-abdominal abscess resistant to antibacterial agents. The E. coli was producing an enzyme, extended-spectrum-beta-lactamase (ESBL), that breaks down cefem-group antibiotics often used in Japan. Therefore, it was resistant to those antimicrobial agents. Detailed analysis was performed by us and researchers of the National Institute of Infectious Diseases, which revealed that the E. coli had a SHV12 genotype of ESBL. It was the first case report of this type of ESBL-producing E. coli infection in Japan. After this experience, I became interested in searching for the mechanism of resistance to antibiotics with various kinds of approaches, such as a method involving genomic analysis by the polymerase-chain reaction (PCR), therapeutic management of drug-resistant bacterial infection, and so on, through which I learned a series of investigative approaches. Since I had plenty of data and experiences generated from routine work, I could perform novel studies and obtained many interesting findings. I am feeding back these findings to routine work in order to improve my performance. From my experience, we should look for the seeds for research from routine work as much as possible, and knowledge and experience generated by resolving problems teaches us how to perform in a clinical setting. This may lead to the further development of our research, which, in turn, promotes the accumulation of knowledge and experience. This feed-forward cycle enables laboratory technicians to improve their quality of work. This I gleaned from my one accidental discovery. PMID:19068786

Nakamura, Tatsuya

2008-10-01

314

The Discovery of Sedna  

NSDL National Science Digital Library

This website, by Caltech astronomer Mike Brown, presents information on Sedna, an object believed to be from the Oort cloud. The site includes a description of the Oort cloud, a history of Sedna's discovery, and a discussion of the new definition of a planet. Illustrations include the discovery image of Sedna.

Brown, Mike

2010-01-05

315

An EU Project on gene flow analysis between crop and wild forms of lettuce and chicory in the context of GMO biosafety: first results in lettuce  

Microsoft Academic Search

An EU project is presented that aims at detecting gene flow between crop and wild forms of lettuce and chicory and possible consequences for the ecology of the wild forms in the light of GMO biosafety assessment. Two novel molecular marker systems, the retrotransposon-based SSAP and the disease resistance gene-based NBS-profiling, were successfully developed for testing their ability to trace

Wiel van de C. C. M; Gerard van der Linden; Nijs den J. C. M; Andrew Flavell; Naeem Syed; Rikke Jorgensen; Francois Felber; Ivan Scotti; J. N. A. M. Rouppe van der Voort; J. Peleman

2003-01-01

316

Rapid Annotation of Anonymous Sequences from Genome Projects Using Semantic Similarities and a Weighting Scheme in Gene Ontology  

PubMed Central

Background Large-scale sequencing projects have now become routine lab practice and this has led to the development of a new generation of tools involving function prediction methods, bringing the latter back to the fore. The advent of Gene Ontology, with its structured vocabulary and paradigm, has provided computational biologists with an appropriate means for this task. Methodology We present here a novel method called ARGOT (Annotation Retrieval of Gene Ontology Terms) that is able to process quickly thousands of sequences for functional inference. The tool exploits for the first time an integrated approach which combines clustering of GO terms, based on their semantic similarities, with a weighting scheme which assesses retrieved hits sharing a certain number of biological features with the sequence to be annotated. These hits may be obtained by different methods and in this work we have based ARGOT processing on BLAST results. Conclusions The extensive benchmark involved 10,000 protein sequences, the complete S. cerevisiae genome and a small subset of proteins for purposes of comparison with other available tools. The algorithm was proven to outperform existing methods and to be suitable for function prediction of single proteins due to its high degree of sensitivity, specificity and coverage. PMID:19247487

Fontana, Paolo; Cestaro, Alessandro; Velasco, Riccardo; Formentin, Elide; Toppo, Stefano

2009-01-01

317

The human decorin gene: Intron-exon organization, discovery of two alternatively spliced exons in the 5[prime] untralsated region, and mapping of the gene to chromosome 12q23  

SciTech Connect

Decorin is a chondroitin/dermatan sulfate proteoglycan expressed by most vascular and avascular connective tissues and, because of its ability to interact with collagen and growth factors, has been implicated in the control of matrix assembly and cellular growth. To understand the molecular mechanisms involved in regulating its tissue expression, we have isolated a number of genomic clones encoding the complete decorin gene. The human decorin gene spans over 38 kb of continuous DNA sequence and contains eight exons and very large introns, two of which are 5.4 and > 13.2 kb. We have discovered two alternatively spliced leader exons, exons Ia and Ib, in the 5[prime] untranslated region. These exons were identified by cloning and sequencing cDNAs obtained by polymerase chain reaction amplification of a fibroblast cDNA library. Using Northern blotting or reverse transcriptase PCR, we detected the two leader exons in a variety of mRNAs isolated from human cell lines and tissues. Interestingly, sequences highly (74-87%) homologous to exons Ia and lb are found in the 5[prime]untranslated region of avian and bovine decorin, respectively. This high degree of conservation among species suggests regulatory functions for these leader exons. In the 3' untranslated region there are several polyadenylation sites, and at least two of these sites could give rise to the transcripts of [approx]1.6 and [approx]1.9 kb, typically detected in a variety of tissues and cells. Using a genomic clone as the labeled probe and in situ hybridization of human metaphase chromosomes, we have mapped the decorin gene to the discrete region of human chromosome 12q23. This sturdy provides the molecular basis for discerning the transcriptional control of the decorin gene and offers the opportunity to investigate genetic disorders linked to this important human gene. 57 refs., 11 figs., 3 tabs.

Danielson, K.G.; Fazzio, A.; Cohen, I.; Cannizzaro, L.A.; Eichstetter, I.; Iozzo, R.V. (Thomas Jefferson Univ., Philadelphia, PA (United States))

1993-01-01

318

Projector-Based Location Discovery and Tracking Johnny Chung Lee  

E-print Network

, projector calibration, augmented reality, location tracking, motion capture, high-speed projection, infrared adding object location discovery and tracking capabilities to commercial projectors. This is accomplishedProjector-Based Location Discovery and Tracking Johnny Chung Lee May 2008 CMU-HCII-08-102 Human

319

YODA: The young observant discovery agent  

SciTech Connect

The YODA project at USC/ISI consists of a group of young researchers who share a passion for autonomous systems that can bootstrap their knowledge of real environments by exploration, experimentation, learning, and discovery. Our goal is to create a mobile agent that can autonomously learn from its environment based on its own actions, percepts, and missions.

Shen, W.M.; Adibi, J.; Cho, Bonghan [and others

1996-12-31

320

Purposive discovery of operations  

NASA Technical Reports Server (NTRS)

The Generate, Prune & Prove (GPP) methodology for discovering definitions of mathematical operators is introduced. GPP is a task within the IL exploration discovery system. We developed GPP for use in the discovery of mathematical operators with a wider class of representations than was possible with the previous methods by Lenat and by Shen. GPP utilizes the purpose for which an operator is created to prune the possible definitions. The relevant search spaces are immense and there exists insufficient information for a complete evaluation of the purpose constraint, so it is necessary to perform a partial evaluation of the purpose (i.e., pruning) constraint. The constraint is first transformed so that it is operational with respect to the partial information, and then it is applied to examples in order to test the generated candidates for an operator's definition. In the GPP process, once a candidate definition survives this empirical prune, it is passed on to a theorem prover for formal verification. We describe the application of this methodology to the (re)discovery of the definition of multiplication for Conway numbers, a discovery which is difficult for human mathematicians. We successfully model this discovery process utilizing information which was reasonably available at the time of Conway's original discovery. As part of this discovery process, we reduce the size of the search space from a computationally intractable size to 3468 elements.

Sims, Michael H.; Bresina, John L.

1992-01-01

321

Dirigent Proteins in Conifer Defense: Gene Discovery, Phylogeny, and Differential Wound and Insect-induced Expression of a Family of DIR and DIR-like Genes in Spruce ( Picea spp.)  

Microsoft Academic Search

The outer stem tissues of conifers provide a durable constitutive and inducible defense barrier consisting of suberized or\\u000a lignified periderm, sclereids, a network of terpenoid-filled resin ducts, and phenolic phloem parenchyma cells. Microarray\\u000a gene expression profiling of Sitka spruce (Picea sitchensis) bark attacked by stem-boring weevils (Pissodes strobi) or through mechanical wounding demonstrated significant accumulation of transcripts resembling dirigent protein

Steven Ralph; Ji-Young Park; Jörg Bohlmann; Shawn D. Mansfield

2006-01-01

322

Learning through Projects.  

ERIC Educational Resources Information Center

Offers guidelines for creating and implementing an age-appropriate project that fits children's needs, interests, and surroundings. Using the example of a supermarket project, outlines the four stages of a project's development--preliminary planning, getting started, investigation and discovery, and wrapping up the project. Gives tips on learning…

Borgia, Eileen

1996-01-01

323

Project COLD.  

ERIC Educational Resources Information Center

Describes Project COLD (Climate, Ocean, Land, Discovery) a scientific study of the Polar Regions, a collection of 35 modules used within the framework of existing subjects: oceanography, biology, geology, meterology, geography, social science. Includes a partial list of topics and one activity (geodesic dome) from a module. (Author/SK)

Kazanjian, Wendy C.

1982-01-01

324

Accelerating scientific discovery : 2007 annual report.  

SciTech Connect

As a gateway for scientific discovery, the Argonne Leadership Computing Facility (ALCF) works hand in hand with the world's best computational scientists to advance research in a diverse span of scientific domains, ranging from chemistry, applied mathematics, and materials science to engineering physics and life sciences. Sponsored by the U.S. Department of Energy's (DOE) Office of Science, researchers are using the IBM Blue Gene/L supercomputer at the ALCF to study and explore key scientific problems that underlie important challenges facing our society. For instance, a research team at the University of California-San Diego/ SDSC is studying the molecular basis of Parkinson's disease. The researchers plan to use the knowledge they gain to discover new drugs to treat the disease and to identify risk factors for other diseases that are equally prevalent. Likewise, scientists from Pratt & Whitney are using the Blue Gene to understand the complex processes within aircraft engines. Expanding our understanding of jet engine combustors is the secret to improved fuel efficiency and reduced emissions. Lessons learned from the scientific simulations of jet engine combustors have already led Pratt & Whitney to newer designs with unprecedented reductions in emissions, noise, and cost of ownership. ALCF staff members provide in-depth expertise and assistance to those using the Blue Gene/L and optimizing user applications. Both the Catalyst and Applications Performance Engineering and Data Analytics (APEDA) teams support the users projects. In addition to working with scientists running experiments on the Blue Gene/L, we have become a nexus for the broader global community. In partnership with the Mathematics and Computer Science Division at Argonne National Laboratory, we have created an environment where the world's most challenging computational science problems can be addressed. Our expertise in high-end scientific computing enables us to provide guidance for applications that are transitioning to petascale as well as to produce software that facilitates their development, such as the MPICH library, which provides a portable and efficient implementation of the MPI standard--the prevalent programming model for large-scale scientific applications--and the PETSc toolkit that provides a programming paradigm that eases the development of many scientific applications on high-end computers.

Beckman, P.; Dave, P.; Drugan, C.

2008-11-14

325

Physiome Project  

NSDL National Science Digital Library

The Physiome Project seeks to facilitate the exchange of information among the research community and to "speed up the discovery of how biological systems work." By acting as a central repository for data and computational models, the project hopes to advance the study of the physiome for the benefit of the scientific community. Along with a description of the physiome and the project, the Web site will include various databases and models organized into categories based on body systems. The site is still under construction, so many of the categories are not yet active. There are also opportunities for researchers to contribute to the project in a variety of ways.

2008-11-04

326

Project Exploration  

NSDL National Science Digital Library

Chicago-based Project Exploration "is the living classroom that involves students and the public in scientific discovery, by connecting kids and families to interactive exhibits, labs, unique science programs and real scientists." Project Exploration focuses on reaching city kids, but every kid (and teachers) should check out this wonderful Web site. Visitors will find tons of activities and features to explore, such as Project Exploration's paleontological expeditions (past and present) and the Mesozoic Garden -- created for the 2003 Chicago Flower and Garden Show. Teachers will also find lesson plans tucked here and there among Project Exploration's dizzying assortment of Web features.

Lyon, Gabrielle; Sereno, Paul

1999-01-01

327

PROJECT: DISCOVERY Research and the Undergrad  

E-print Network

;1614 The Man Called Kaz He arrived in the fall of 1978, a gangly freshman with a bowl cut. The Vikes basketball and cultural landscape of 1968. B Y GRAN T K E RR Seven Flames Editor's note President's Message David Turpin Campus News and Culture Letter to Japan · Cold War slides · Helping Honduras · OceanGybe · LSQ at 25

Pedersen, Tom

328

Discovery Park Undergraduate Research Internship Projects  

E-print Network

disease-causing organisms · Work as a metadata editor to improve an online collection of video and image · Pharmaceutical Development · Aeronautics and Rocket Propulsion · Computer Simulation Programming · Medical

329

The Discovery of Noggin.  

ERIC Educational Resources Information Center

Discusses recently published work that appears to have many of the answers to the question of how the nervous system develops. Focuses on the discovery of what is believed to be neural inducer, a protein called noggin. (LZ)

Oppenheimer, Steven B.

1995-01-01

330

Platforms for antibiotic discovery.  

PubMed

The spread of resistant bacteria, leading to untreatable infections, is a major public health threat but the pace of antibiotic discovery to combat these pathogens has slowed down. Most antibiotics were originally isolated by screening soil-derived actinomycetes during the golden era of antibiotic discovery in the 1940s to 1960s. However, diminishing returns from this discovery platform led to its collapse, and efforts to create a new platform based on target-focused screening of large libraries of synthetic compounds failed, in part owing to the lack of penetration of such compounds through the bacterial envelope. This article considers strategies to re-establish viable platforms for antibiotic discovery. These include investigating untapped natural product sources such as uncultured bacteria, establishing rules of compound penetration to enable the development of synthetic antibiotics, developing species-specific antibiotics and identifying prodrugs that have the potential to eradicate dormant persisters, which are often responsible for hard-to-treat infections. PMID:23629505

Lewis, Kim

2013-05-01

331

The requirements discovery process  

SciTech Connect

Cost and schedule overruns are often caused by poor requirements that are produced by people who do not understand the requirement process. This paper provides a high-level overview of the requirements discovery process.

Bahill, A.T. [Univ. of Arizona, Tucson, AZ (United States). Systems and Industrial Engineering; Dean, F.F. [Sandia National Lab., Albuquerque, NM (United States)

1997-02-01

332

Organic Indoor Location Discovery  

E-print Network

We describe an indoor, room-level location discovery method based on spatial variations in "wifi signatures," i.e., MAC addresses and signal strengths of existing wireless access points. The principal novelty of our system ...

Hicks, Jamey

2008-12-30

333

Discovery Collection: Oyster Shells  

NSDL National Science Digital Library

Oyster Shells is one of the AMNH Education Department's many collections of specimens and artifacts gathered the world over by explorers and scientists. In its online Discovery Collection form, Oyster Shells includes photographs of 15 specimens with classification and distribution details, an interactive key that guides you through specimen identification, an activity where students select and identify a specimen photograph using the interactive identification key and an Educator's Guide with suggestions for how to use the Oyster Shells Discovery Collection in the classroom.

Breslof, Lisa; Schiller, William

334

Discovery Collection: Marine Animals  

NSDL National Science Digital Library

Marine Animals is one of the AMNH Education Department's many collections of specimens and artifacts gathered the world over by explorers and scientists. In its online Discovery Collection form, Marine Animals includes photographs of 20 specimens with classification and distribution details, an interactive key that guides you through specimen identification, an activity where students select and identify a specimen photograph using the interactive identification key and an Educator's Guide with suggestions for how to use the Marine Animals Discovery Collection in the classroom.

Breslof, Lisa; Schiller, William

335

NK cell-based approach for screening novel functional immune genes.  

PubMed

The human genome project provides extensive opportunities for the discovery of novel functional immune genes. In order to find innate immune genes that might regulate the function of NK cells from a cDNA library, we used an NK cell line, NK-92, as a platform to screen candidate genes. After comparing with other gene transfer methods, electroporation was selected as the best gene transfection approach to deliver cDNA expression plasmids containing candidate genes into the NK-92 cells. When the transferred gene was stably expressed in NK-92 cells, the functional changes in the NK-92 cells were examined, including cytotoxicity, cytolytic molecules, cytokine production, and proliferation. Two novel genes were selected as functional genes that regulate NK cell function from among more than 100 candidate genes, for which the proliferation and cytotoxicity of NK-92 cells were examined as primary indicators. This was followed by extensive flow cytometry analysis and RT-PCR. The primary data indicated that the two novel genes negatively influenced the cytotoxicity of NK-92 cells by inhibiting the expression of several activating receptors and immune functional genes. Therefore, we describe an efficient method for the discovery of novel functional genes in NK cells by using an NK cell line as a screening platform. PMID:21168542

Wu, Longyan; Zhang, Cai; Tian, Zhigang; Zhang, Jian

2011-02-01

336

THE DISCOVERY OF ALGORITHMIC PROBABILITY  

E-print Network

THE DISCOVERY OF ALGORITHMIC PROBABILITY Ray J. Solomono# # Royal Holloway, University of London will describe a voyage of discovery --- the discovery of Algorithmic Probability. But before I describe, the motivation is discovery itself --- the joy of ``going where no one has gone before'' --- the excitement

Solomonoff, Ray

337

THE DISCOVERY OF ALGORITHMIC PROBABILITY  

E-print Network

THE DISCOVERY OF ALGORITHMIC PROBABILITY Ray J. Solomonoff Royal Holloway, University of London will describe a voyage of discovery -- the discovery of Algorithmic Probability. But before I describe, the motivation is discovery itself -- the joy of "going where no one has gone before" -- the excitement

Solomonoff, Ray

338

BioGraph: unsupervised biomedical knowledge discovery via automated hypothesis generation  

PubMed Central

We present BioGraph, a data integration and data mining platform for the exploration and discovery of biomedical information. The platform offers prioritizations of putative disease genes, supported by functional hypotheses. We show that BioGraph can retrospectively confirm recently discovered disease genes and identify potential susceptibility genes, outperforming existing technologies, without requiring prior domain knowledge. Additionally, BioGraph allows for generic biomedical applications beyond gene discovery. BioGraph is accessible at http://www.biograph.be. PMID:21696594

2011-01-01

339

Knowledge discovery by accuracy maximization  

PubMed Central

Here we describe KODAMA (knowledge discovery by accuracy maximization), an unsupervised and semisupervised learning algorithm that performs feature extraction from noisy and high-dimensional data. Unlike other data mining methods, the peculiarity of KODAMA is that it is driven by an integrated procedure of cross-validation of the results. The discovery of a local manifold’s topology is led by a classifier through a Monte Carlo procedure of maximization of cross-validated predictive accuracy. Briefly, our approach differs from previous methods in that it has an integrated procedure of validation of the results. In this way, the method ensures the highest robustness of the obtained solution. This robustness is demonstrated on experimental datasets of gene expression and metabolomics, where KODAMA compares favorably with other existing feature extraction methods. KODAMA is then applied to an astronomical dataset, revealing unexpected features. Interesting and not easily predictable features are also found in the analysis of the State of the Union speeches by American presidents: KODAMA reveals an abrupt linguistic transition sharply separating all post-Reagan from all pre-Reagan speeches. The transition occurs during Reagan’s presidency and not from its beginning. PMID:24706821

Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

2014-01-01

340

Knowledge discovery by accuracy maximization.  

PubMed

Here we describe KODAMA (knowledge discovery by accuracy maximization), an unsupervised and semisupervised learning algorithm that performs feature extraction from noisy and high-dimensional data. Unlike other data mining methods, the peculiarity of KODAMA is that it is driven by an integrated procedure of cross-validation of the results. The discovery of a local manifold's topology is led by a classifier through a Monte Carlo procedure of maximization of cross-validated predictive accuracy. Briefly, our approach differs from previous methods in that it has an integrated procedure of validation of the results. In this way, the method ensures the highest robustness of the obtained solution. This robustness is demonstrated on experimental datasets of gene expression and metabolomics, where KODAMA compares favorably with other existing feature extraction methods. KODAMA is then applied to an astronomical dataset, revealing unexpected features. Interesting and not easily predictable features are also found in the analysis of the State of the Union speeches by American presidents: KODAMA reveals an abrupt linguistic transition sharply separating all post-Reagan from all pre-Reagan speeches. The transition occurs during Reagan's presidency and not from its beginning. PMID:24706821

Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

2014-04-01

341

Whole-genome Comparative Annotation and Regulatory Motif Discovery in Multiple Yeast Species  

E-print Network

Whole-genome Comparative Annotation and Regulatory Motif Discovery in Multiple Yeast Species these three yeast species to their close relative, S. cerevisiae. Genome-wide comparative analysis allowed than 90% of genes despite the large number of duplicated genes in the yeast genome, and the discovery

Kellis, Manolis

342

Metagenomic gene discovery: past, present and future  

Microsoft Academic Search

It is now widely accepted that the application of standard microbiological methods for the recovery of microorganisms from the environment has had limited success in providing access to the true extent of microbial biodiversity. It follows that much of the extant microbial genetic diversity (collectively termed the metagenome) remains unexploited, an issue of con- siderable relevance to a wider understanding

Don Cowan; Quinton Meyer; William Stafford; Samson Muyanga; Rory Cameron; Pia Wittwer

2005-01-01

343

Moments of Discovery  

NSDL National Science Digital Library

Even the most cursory explorations into how scientific discoveries are made reveals that many of these discoveries are tinged with a certain serendipity and circumstances that are not immediately attributable to a wholly reasoned and logical progression of methodical experiments. Presented by the American Institute of Physics, this online multimedia exhibit tells the story of two important 20th century scientific discoveries: the discovery of nuclear fission and the detection of the first optical pulsar. The discovery of nuclear fission section contains audio clips from some of those responsible for this scientific endeavor, including Enrico Fermi, Arthur Holly Compton, and Otto Hahn. One particularly noteworthy clip features Compton's firsthand recollection of the first successful self-sustaining nuclear chain reaction under the bleacher of Stagg Field on the campus of the University of Chicago. The second exhibit hones in on the detection of the first optical pulsar, and includes clips from Philip Morrison, John Cocke, and Michael Disney. The site is rounded out by a set of teachers' guides designed to complement these online exhibits.

344

A Decade of Discovery  

SciTech Connect

This book provides a fascinating account of some of the most significant scientific discoveries and technological innovations coming out of the U.S. Department of Energy’s National Laboratories. This remarkable book illustrates how the men and women of the National Laboratories are keeping us on the cutting edge. Though few Americans are familiar with the scope and scale of the work conducted at these National Laboratories, their research is literally changing our lives and bettering our planet. The book describes the scientific discoveries and technological advancements "in recognition of the men and women working in DOE's seventeen national laboratories across the country." Through highly vivid and accessible stories, this book details recent breakthroughs in three critical areas: 1) Energy and Environment, 2) National Security and 3) Life and Physical Science. The book illustrates how this government-funded research has resulted in more energy-efficient buildings; new, cleaner alternative fuels that reduce greenhouse gas emissions; safer, more efficient, nuclear power plants; improved responses to disease outbreaks; more secure and streamlined airport security; more effective treatments for cancer and other diseases; and astonishing discoveries that are altering our understanding of the universe and enabling scientific breakthroughs in fields such as nanotechnology and particle physics. Specifically, it contains 37 stories. A Decade of Discovery is truly a recent history of discovery - and a fascinating look at what the next decade holds.

none,

2008-01-01

345

Recent and Projected Increases in Atmospheric CO2 Concentration Can Enhance Gene Flow between Wild and Genetically Altered Rice (Oryza sativa)  

PubMed Central

Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO2 between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO2 from an early 20th century concentration (300 µmol mol?1) to current (400 µmol mol?1) and projected, mid-21st century (600 µmol mol?1) values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol?1. The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO2 also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO2 could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems. PMID:22649533

Ziska, Lewis H.; Gealy, David R.; Tomecek, Martha B.; Jackson, Aaron K.; Black, Howard L.

2012-01-01

346

DiscoveryResources.org  

NSDL National Science Digital Library

An interesting site that is packed full of up-to-date info, discoveryresources.org is "where you will find the most up-to-date information, resources and news available about electronic discovery...(the site) offers much needed resources for legal professionals who seek to understand the many new technological and legal challenges associated with electronic discovery." As fast as the technology revolution is booming, so too is are all of the legal strings attached. This site seeks to provide professionals in the field with a means to stay up on discovery news. With links to Legal News, Featured Articles, a weblog, and a Reading Room, there is lots of useful information on this unique site.

347

Exploring the Planets: Discovery  

NSDL National Science Digital Library

This site describes what early civilizations knew about our solar system and how astronomy developed over the centuries. The early theories describing the movements of the planets, development of the first telescopes, and discoveries of the planets Uranus, Neptune and Pluto are some of the topics addressed in Discovery. Here you will find the Pluto discovery plate, the photographic plate taken the day Pluto's position was discovered by Clyde Tombaugh. Other topics covered at this site include: the Renaissance with the ideas of Copernicus and Kepler; the age of the telescope, which traces its development; Galileo, who is credited with discovering the moons of Jupiter, phases of Venus, and the craters on the Moon; and planetary satellites.

348

Discovery of Companion Asteroids  

NSDL National Science Digital Library

This site displays the first-ever images of a large, double asteroid once assumed to be a single asteroid called Antiope. The images were recently released by the Southwest Research Institute (SWRI). Each asteroid in the pair is approximately 50 miles across, separated by about 100 miles. This discovery was made using the W.M. Keck Observatory, Mauna Kea, Hawaii. Images of another discovery, that of a small moon orbiting the large asteroid Pulcova, is featured at this site. In addition to still images, movies show the motion of the asteroids.

1999-01-01

349

Titanic: Discovery Channel  

NSDL National Science Digital Library

RMS Titanic raised a 23- by 14-foot section of the Titanic's outer hull this week, and the Discovery Channel, who helped sponsor the expedition, will be webcasting live from the interior of the Titanic via robot cameras August 16 at 8:00 and 10:00 p.m. (Eastern Time). In addition to their live webcase, the Discovery Channel site (discussed in the December 5, 1997 issue of the Scout Report) features virtual reality tours of sections of the Titanic before and after its crash, quicktime videos of the expeditions, a computer animated simulation of the crash, and more.

350

Discovery Corps Fellowships (DCF)  

NSF Publications Database

... need. Their projects enhance research capacity and infrastructure and contribute to workforce ... need. Their projects will enhance research capacity and infrastructure and contribute to workforce ...

351

Analysis of 4,664 high-quality sequence-finished poplar full-length cDNA clones and their utility for the discovery of genes responding to insect feeding  

PubMed Central

Background The genus Populus includes poplars, aspens and cottonwoods, which will be collectively referred to as poplars hereafter unless otherwise specified. Poplars are the dominant tree species in many forest ecosystems in the Northern Hemisphere and are of substantial economic value in plantation forestry. Poplar has been established as a model system for genomics studies of growth, development, and adaptation of woody perennial plants including secondary xylem formation, dormancy, adaptation to local environments, and biotic interactions. Results As part of the poplar genome sequencing project and the development of genomic resources for poplar, we have generated a full-length (FL)-cDNA collection using the biotinylated CAP trapper method. We constructed four FLcDNA libraries using RNA from xylem, phloem and cambium, and green shoot tips and leaves from the P. trichocarpa Nisqually-1 genotype, as well as insect-attacked leaves of the P. trichocarpa × P. deltoides hybrid. Following careful selection of candidate cDNA clones, we used a combined strategy of paired end reads and primer walking to generate a set of 4,664 high-accuracy, sequence-verified FLcDNAs, which clustered into 3,990 putative unique genes. Mapping FLcDNAs to the poplar genome sequence combined with BLAST comparisons to previously predicted protein coding sequences in the poplar genome identified 39 FLcDNAs that likely localize to gaps in the current genome sequence assembly. Another 173 FLcDNAs mapped to the genome sequence but were not included among the previously predicted genes in the poplar genome. Comparative sequence analysis against Arabidopsis thaliana and other species in the non-redundant database of GenBank revealed that 11.5% of the poplar FLcDNAs display no significant sequence similarity to other plant proteins. By mapping the poplar FLcDNAs against transcriptome data previously obtained with a 15.5 K cDNA microarray, we identified 153 FLcDNA clones for genes that were differentially expressed in poplar leaves attacked by forest tent caterpillars. Conclusion This study has generated a high-quality FLcDNA resource for poplar and the third largest FLcDNA collection published to date for any plant species. We successfully used the FLcDNA sequences to reassess gene prediction in the poplar genome sequence, perform comparative sequence annotation, and identify differentially expressed transcripts associated with defense against insects. The FLcDNA sequences will be essential to the ongoing curation and annotation of the poplar genome, in particular for targeting gaps in the current genome assembly and further improvement of gene predictions. The physical FLcDNA clones will serve as useful reagents for functional genomics research in areas such as analysis of gene functions in defense against insects and perennial growth. Sequences from this study have been deposited in NCBI GenBank under the accession numbers EF144175 to EF148838. PMID:18230180

Ralph, Steven G; Chun, Hye Jung E; Cooper, Dawn; Kirkpatrick, Robert; Kolosova, Natalia; Gunter, Lee; Tuskan, Gerald A; Douglas, Carl J; Holt, Robert A; Jones, Steven JM; Marra, Marco A; Bohlmann, Jorg

2008-01-01

352

Accelerating the Rate of Astronomical Discovery  

NASA Astrophysics Data System (ADS)

Special Session 5 on Accelerating the Rate of Astronomical Discovery addressed a range of potential limits to progress - paradigmatic, technological, organisational, and political - examining each issue both from modern and historical perspectives, and drawing lessons to guide future progress. A number of issues were identified which potentially regulate the flow of discoveries, such as the balance between large strongly-focussed projects and instruments, designed to answer the most fundamental questions confronting us, and the need to maintain a creative environment with room for unorthodox thinkers and bold, high risk, projects. Also important is the need to maintain historical and cultural perspectives, and the need to engage the minds of the most brilliant young people on the planet, regardless of their background, ethnicity, gender, or geography.

Norris, Ray P. Ruggles, Clive L. N.

2010-05-01

353

Discovery Education: A Definition.  

ERIC Educational Resources Information Center

Discovery Education is based on the writings of Henry David Thoreau, an early champion of experiential learning. After 2 months of preparation, 10th-grade students spent 4 days in the wilderness reenacting a piece of history, such as the Lewis and Clark Expedition. The interdisciplinary approach always included journal-writing. Students gained…

Wilson, Harold C.

2002-01-01

354

Interoperability and information discovery  

USGS Publications Warehouse

In the context of information systems, there is interoperability when the distinctions between separate information systems are not a barrier to accomplishing a task that spans those systems. Interoperability so defined implies that there are commonalities among the systems involved and that one can exploit such commonalities to achieve interoperability. The challenge of a particular interoperability task is to identify relevant commonalities among the systems involved and to devise mechanisms that exploit those commonalities. The present paper focuses on the particular interoperability task of information discovery. The Global Information Locator Service (GILS) is described as a policy, standards, and technology framework for addressing interoperable information discovery on a global and long-term basis. While there are many mechanisms for people to discover and use all manner of data and information resources, GILS initiatives exploit certain key commonalities that seem to be sufficient to realize useful information discovery interoperability at a global, long-term scale. This paper describes ten of the specific commonalities that are key to GILS initiatives. It presents some of the practical implications for organizations in various roles: content provider, system engineer, intermediary, and searcher. The paper also provides examples of interoperable information discovery as deployed using GILS in four types of information communities: bibliographic, geographic, environmental, and government.

Christian, E.

2001-01-01

355

Political Discovery Resource Book.  

ERIC Educational Resources Information Center

This resource book for secondary students describes various aspects of federal, state, and local political processes. Originally written for use in the magnet education program "Political Discovery" in Boston, Massachusetts, the book can easily be used or adapted by teachers in any state. The first part of the book deals with the federal…

Political Discovery Education Collaborative for Greater Boston, MA.

356

Knowledge Discovery from Networks  

Microsoft Academic Search

Nowadays, network becomes the engine of scientific research activities in 21st century. For example, a Web search engine is something to do with networked data mining and knowledge discovery from networks in deed. Networks interact with one another and are recursive. We have come to grasp the important knowledge of networks. Network is the key to representing the complex world

Deyi Li

2008-01-01

357

The Discovery Way  

ERIC Educational Resources Information Center

At the Center for Discovery (The Center), a private, non-profit agency 80 miles northwest of New York City in the Catskill Mountains, children are growing and learning at their own pace, in their own way, with careful attention focused on communication and social/emotional development. Children with autism are being educated to be social beings,…

Hamlin, Theresa

2005-01-01

358

Consistent Knowledge Discovery in  

E-print Network

retrospective analyses have found error rates ranging from 20% to 43%. These data clearly demonstrate the needConsistent Knowledge Discovery in Medical Diagnosis Eliminating Contradictions Among Rules in the medical field, some of which have originated in the artificial intelligence area. In this arti- cle, we

Kovalerchuk, Boris

359

Discoveries Change Agents  

E-print Network

Discoveries Change Agents A new kind of researcher moves from practice to research to policy) "is to graduate `change agents' who are able to bridge the worlds of research and academia, clinical in this area presently." That situation is changing because of the Scholars in HeAlth Research Program (SHARP

Shihadeh, Alan

360

The Discovery of Quarks  

Microsoft Academic Search

Quarks are widely recognized today as being among the elementary particles of which matter is composed. The key evidence for their existence came from a series of inelastic electron-nucleon scattering experiments conducted between 1967 and 1973 at the Stanford Linear Accelerator Center. Other theoretical and experimental advances of the 1970s confirmed this discovery, leading to the present standard model of

Michael Riordan

1992-01-01

361

discoveries in drugs and  

E-print Network

New discoveries in drugs and medicinal products are happening rapidly.One of the greatest that developing new drugs requires an enormous amount of time and money. On av- erage, introducing a new drug product to market takes approximately 15 years and $650 million. A drug product consists of therapeutics

Glasser, Benjamin J.

362

Open source drug discovery - a limited tutorial.  

PubMed

Open science is a new concept for the practice of experimental laboratory-based research, such as drug discovery. The authors have recently gained experience in how to run such projects and here describe some straightforward steps others may wish to take towards more openness in their own research programmes. Existing and inexpensive online tools can solve many challenges, while some psychological barriers to the free sharing of all data and ideas are more substantial. PMID:23985301

Robertson, Murray N; Ylioja, Paul M; Williamson, Alice E; Woelfle, Michael; Robins, Michael; Badiola, Katrina A; Willis, Paul; Olliaro, Piero; Wells, Timothy N C; Todd, Matthew H

2014-01-01

363

Wheat gene bank accessions as a source of new alleles of the powdery mildew resistance gene Pm3: a large scale allele mining project  

PubMed Central

Background In the last hundred years, the development of improved wheat cultivars has led to the replacement of landraces and traditional varieties by modern cultivars. This has resulted in a decline in the genetic diversity of agriculturally used wheat. However, the diversity lost in the elite material is somewhat preserved in crop gene banks. Therefore, the gene bank accessions provide the basis for genetic improvement of crops for specific traits and and represent rich sources of novel allelic variation. Results We have undertaken large scale molecular allele mining to isolate new alleles of the powdery mildew resistance gene Pm3 from wheat gene bank accessions. The search for new Pm3 alleles was carried out on a geographically diverse set of 733 wheat accessions originating from 20 countries. Pm3 specific molecular tools as well as classical pathogenicity tests were used to characterize the accessions. Two new functional Pm3 alleles were identified out of the eight newly cloned Pm3 sequences. These new resistance alleles were isolated from accessions from China and Nepal. Thus, the repertoire of functional Pm3 alleles now includes 17 genes, making it one of the largest allelic series of plant resistance genes. The combined information on resistant and susceptible Pm3 sequences will allow to study molecular function and specificity of functional Pm3 alleles. Conclusions This study demonstrates that molecular allele mining on geographically defined accessions is a useful strategy to rapidly characterize the diversity of gene bank accessions at a specific genetic locus of agronomical importance. The identified wheat accessions with new resistance specificities can be used for marker-assisted transfer of the Pm3 alleles to modern wheat lines. PMID:20470444

2010-01-01

364

Serendipitous Science: An Unexpected Discovery  

NSDL National Science Digital Library

This article describes glaciologist Lonnie Thompson's discovery of an ancient plant in Peru. It also illustrates some important characteristics of good science that can be seen even in a serendipitous discovery.

Landis, Carol

365

Synthetic Biology of Antimicrobial Discovery  

E-print Network

Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future ...

Zakeri, Bijan

366

The Knockout Mouse Project  

Microsoft Academic Search

Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways,

James F Battey; Allan Bradley; Maja Bucan; Mario Capecchi; Francis S Collins; William F Dove; Geoffrey Duyk; Susan Dymecki; Janan T Eppig; Franziska B Grieder; Nathaniel Heintz; Geoff Hicks; Thomas R Insel; Alexandra Joyner; Beverly H Koller; K C Kent Lloyd; Terry Magnuson; Mark W Moore; Andras Nagy; Jonathan D Pollock; Allen D Roses; Arthur T Sands; Brian Seed; William C Skarnes; Jay Snoddy; Philippe Soriano; David J Stewart; Francis Stewart; Bruce Stillman; Harold Varmus; Lyuba Varticovski; Inder M Verma; Thomas F Vogt; Harald von Melchner; Jan Witkowski; Richard P Woychik; Wolfgang Wurst; George D Yancopoulos; Stephen G Young; Brian Zambrowicz; Christopher P Austin

2004-01-01

367

Results of a Regular Competition on the Discovery Program  

Microsoft Academic Search

The results of a regular competition of space-flight projects on the Discovery program are pre- sented. Five projects are declared winners, namely: (1) Aladdin, returning samples from Martian moons Phobos and Deimos; (2) CONTOUR, obtaining images and spectra of three comets from a close distance and an onboard analysis of cometary dust; (3) Genesis, collecting and returning solar-wind particles to

A. T. Basilevsky

1997-01-01

368

Science Fun with Electricity...Discoveries and Innovations.  

ERIC Educational Resources Information Center

This project manual is written for 4-H member children who are in the fifth grade or older. This project is designed to familiarize members with the scientific history concerning the discovery and application of electric energy through the 1800's. Readers can conduct experiments similar to the ones performed by the scientists and inventors of that…

Horton, Robert L.

369

Discovery: Gear & Gadgets Videos  

NSDL National Science Digital Library

Do you want to learn about soy surfboards? How text messages might save lives? Or about how a therapeutic war game might help veterans? All of this and much more is available on the Discovery Channel's Gear & Gadgets website. Each video is a few minutes in length, and visitors can search through the collection of 31 videos by name or subject. Users can use the Show Me toolbar to look for clips, existing playlists, and full episodes. The Tech videos are informative, and visitors would do well to look at Underwater Turbines Pump Out Energy and Truckin' From Diesel to Veg Oil. Finally, the site also includes updates from other Discovery video channels, including clips on new medical technologies and aerospace innovations.

370

Challenges of Antibacterial Discovery  

PubMed Central

Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort. PMID:21233508

Silver, Lynn L.

2011-01-01

371

Opportunistic Adaptation Knowledge Discovery  

Microsoft Academic Search

Adaptation has long been considered as the Achilles' heel of case-based\\u000areasoning since it requires some domain-specific knowledge that is difficult to\\u000aacquire. In this paper, two strategies are combined in order to reduce the\\u000aknowledge engineering cost induced by the adaptation knowledge (CA) acquisition\\u000atask: CA is learned from the case base by the means of knowledge discovery\\u000atechniques,

Fadi Badra; Amélie Cordier; Jean Lieber

2009-01-01

372

Discovery as a process  

SciTech Connect

The three great myths, which form a sort of triumvirate of misunderstanding, are the Eureka! myth, the hypothesis myth, and the measurement myth. These myths are prevalent among scientists as well as among observers of science. The Eureka! myth asserts that discovery occurs as a flash of insight, and as such is not subject to investigation. This leads to the perception that discovery or deriving a hypothesis is a moment or event rather than a process. Events are singular and not subject to description. The hypothesis myth asserts that proper science is motivated by testing hypotheses, and that if something is not experimentally testable then it is not scientific. This myth leads to absurd posturing by some workers conducting empirical descriptive studies, who dress up their study with a ``hypothesis`` to obtain funding or get it published. Methods papers are often rejected because they do not address a specific scientific problem. The fact is that many of the great breakthroughs in silence involve methods and not hypotheses or arise from largely descriptive studies. Those captured by this myth also try to block funding for those developing methods. The third myth is the measurement myth, which holds that determining what to measure is straightforward, so one doesn`t need a lot of introspection to do science. As one ecologist put it to me ``Don`t give me any of that philosophy junk, just let me out in the field. I know what to measure.`` These myths lead to difficulties for scientists who must face peer review to obtain funding and to get published. These myths also inhibit the study of science as a process. Finally, these myths inhibit creativity and suppress innovation. In this paper I first explore these myths in more detail and then propose a new model of discovery that opens the supposedly miraculous process of discovery to doser scrutiny.

Loehle, C.

1994-05-01

373

Planetary Science Resource Discoveries  

NSDL National Science Digital Library

Planetary Science Research Discoveries (PSRD) is an educational site sharing the latest research on meteorites, planets, and other solar system bodies being made by NASA-sponsored scientists. The web site is supported by the Cosmochemistry Program of NASA's Science Mission Directorate and by Hawai'i Space Grant Consortium. The site features useful links related to planetary and space sciences. Links to internal pages as well as other sites are searchable by topic. The site also includes a glossary.

Taylor, G. J.; Martel, Linda M.; Planetary Science Research Discoveries, University O.

374

43 CFR 4.1130 - Discovery methods.  

Code of Federal Regulations, 2013 CFR

... 1 2013-10-01 2013-10-01 false Discovery methods. 4.1130 Section 4.1130 Public...Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by...

2013-10-01

375

49 CFR 1503.633 - Discovery.  

Code of Federal Regulations, 2010 CFR

... 2010-10-01 2010-10-01 false Discovery. 1503.633 Section 1503.633 Transportation...in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery...

2010-10-01

376

49 CFR 1503.633 - Discovery.  

Code of Federal Regulations, 2012 CFR

... 2012-10-01 2012-10-01 false Discovery. 1503.633 Section 1503.633 Transportation...in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery...

2012-10-01

377

Discovery Park Impact Network for Photovoltaic Technology  

E-print Network

Discovery Park Impact Network for Photovoltaic Technology NEED Discovery Park provides opportunities to create large-scale, interdisciplinary centers to address social challenges. One Discovery Park tool to facilitate interdisciplinary faculty collaborations is the Discovery Lecture Series, funded

Holland, Jeffrey

378

14 CFR 13.220 - Discovery.  

Code of Federal Regulations, 2010 CFR

... 2010-01-01 2010-01-01 false Discovery. 13.220 Section 13.220 Aeronautics...Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery...

2010-01-01

379

14 CFR 13.220 - Discovery.  

Code of Federal Regulations, 2013 CFR

... 2013-01-01 2013-01-01 false Discovery. 13.220 Section 13.220 Aeronautics...Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery...

2013-01-01

380

43 CFR 4.1130 - Discovery methods.  

Code of Federal Regulations, 2012 CFR

... 1 2012-10-01 2011-10-01 true Discovery methods. 4.1130 Section 4.1130 Public...Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by...

2012-10-01

381

49 CFR 1503.633 - Discovery.  

Code of Federal Regulations, 2011 CFR

... 2011-10-01 2011-10-01 false Discovery. 1503.633 Section 1503.633 Transportation...in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery...

2011-10-01

382

14 CFR 13.220 - Discovery.  

Code of Federal Regulations, 2012 CFR

... 2012-01-01 2012-01-01 false Discovery. 13.220 Section 13.220 Aeronautics...Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery...

2012-01-01

383

49 CFR 1503.633 - Discovery.  

Code of Federal Regulations, 2013 CFR

... 2013-10-01 2013-10-01 false Discovery. 1503.633 Section 1503.633 Transportation...in TSA Civil Penalty Actions § 1503.633 Discovery. (a) Initiation of discovery. Any party may initiate discovery...

2013-10-01

384

14 CFR 13.220 - Discovery.  

Code of Federal Regulations, 2011 CFR

... 2011-01-01 2011-01-01 false Discovery. 13.220 Section 13.220 Aeronautics...Practice in FAA Civil Penalty Actions § 13.220 Discovery. (a) Initiation of discovery. Any party may initiate discovery...

2011-01-01

385

43 CFR 4.1130 - Discovery methods.  

... 1 2014-10-01 2014-10-01 false Discovery methods. 4.1130 Section 4.1130 Public...Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by...

2014-10-01

386

43 CFR 4.1130 - Discovery methods.  

Code of Federal Regulations, 2011 CFR

... 1 2011-10-01 2011-10-01 false Discovery methods. 4.1130 Section 4.1130 Public...Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by...

2011-10-01

387

43 CFR 4.1130 - Discovery methods.  

Code of Federal Regulations, 2010 CFR

... 1 2010-10-01 2010-10-01 false Discovery methods. 4.1130 Section 4.1130 Public...Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by...

2010-10-01

388

42 CFR 405.1037 - Discovery.  

Code of Federal Regulations, 2013 CFR

...to request discovery or conduct discovery only if the requesting party establishes...fault in not meeting the original discovery deadline. (5) If the ALJ grants...extension request, it must impose a new discovery deadline and, if necessary,...

2013-10-01

389

42 CFR 405.1037 - Discovery.  

Code of Federal Regulations, 2012 CFR

...to request discovery or conduct discovery only if the requesting party establishes...fault in not meeting the original discovery deadline. (5) If the ALJ grants...extension request, it must impose a new discovery deadline and, if necessary,...

2012-10-01

390

42 CFR 405.1037 - Discovery.  

Code of Federal Regulations, 2011 CFR

...to request discovery or conduct discovery only if the requesting party establishes...fault in not meeting the original discovery deadline. (5) If the ALJ grants...extension request, it must impose a new discovery deadline and, if necessary,...

2011-10-01

391

42 CFR 405.1037 - Discovery.  

Code of Federal Regulations, 2010 CFR

...to request discovery or conduct discovery only if the requesting party establishes...fault in not meeting the original discovery deadline. (5) If the ALJ grants...extension request, it must impose a new discovery deadline and, if necessary,...

2010-10-01

392

The language of discovery  

PubMed Central

Discovery, as a public attribution, and discovering, the act of conducting research, are experiences that entail “languaging” the unknown. This distinguishing property of language ? its ability to bring forth, out of the unspoken realm, new knowledge, original ideas, and novel thinking – is essential to the discovery process. In sharing their ideas and views, scientists create co?negotiated linguistic distinctions that prompt the revision of established mental maps and the adoption of new ones. While scientific mastery entails command of the conversational domain unique to a specific discipline, there is an emerging conversational domain that must be mastered that goes beyond the language unique to any particular specialty. Mastery of this new conversational domain gives researchers access to their hidden mental maps that limit their ways of thinking about and doing science. The most effective scientists use language to recontextualize their approach to problem?solving, which triggers new insights (previously unavailable) that result in new discoveries. While language is not a replacement for intuition and other means of knowing, when we try to understand what’s outside of language we have to use language to do so. PMID:21688238

Souba, Wiley

2011-01-01

393

Bayesian Centroid Estimation for Motif Discovery  

PubMed Central

Biological sequences may contain patterns that signal important biomolecular functions; a classical example is regulation of gene expression by transcription factors that bind to specific patterns in genomic promoter regions. In motif discovery we are given a set of sequences that share a common motif and aim to identify not only the motif composition, but also the binding sites in each sequence of the set. We propose a new centroid estimator that arises from a refined and meaningful loss function for binding site inference. We discuss the main advantages of centroid estimation for motif discovery, including computational convenience, and how its principled derivation offers further insights about the posterior distribution of binding site configurations. We also illustrate, using simulated and real datasets, that the centroid estimator can differ from the traditional maximum a posteriori or maximum likelihood estimators. PMID:24324603

Carvalho, Luis

2013-01-01

394

The Consensus Coding Sequence (Ccds) Project: Identifying a Common Protein-Coding Gene Set for the Human and Mouse Genomes  

E-print Network

Effective use of the human and mouse genomes requires reliable identification of genes and their products. Although multiple public resources provide annotation, different methods are used that can result in similar but ...

Kellis, Manolis

395

Efficient exact motif discovery  

PubMed Central

Motivation: The motif discovery problem consists of finding over-represented patterns in a collection of biosequences. It is one of the classical sequence analysis problems, but still has not been satisfactorily solved in an exact and efficient manner. This is partly due to the large number of possibilities of defining the motif search space and the notion of over-representation. Even for well-defined formalizations, the problem is frequently solved in an ad hoc manner with heuristics that do not guarantee to find the best motif. Results: We show how to solve the motif discovery problem (almost) exactly on a practically relevant space of IUPAC generalized string patterns, using the p-value with respect to an i.i.d. model or a Markov model as the measure of over-representation. In particular, (i) we use a highly accurate compound Poisson approximation for the null distribution of the number of motif occurrences. We show how to compute the exact clump size distribution using a recently introduced device called probabilistic arithmetic automaton (PAA). (ii) We define two p-value scores for over-representation, the first one based on the total number of motif occurrences, the second one based on the number of sequences in a collection with at least one occurrence. (iii) We describe an algorithm to discover the optimal pattern with respect to either of the scores. The method exploits monotonicity properties of the compound Poisson approximation and is by orders of magnitude faster than exhaustive enumeration of IUPAC strings (11.8 h compared with an extrapolated runtime of 4.8 years). (iv) We justify the use of the proposed scores for motif discovery by showing our method to outperform other motif discovery algorithms (e.g. MEME, Weeder) on benchmark datasets. We also propose new motifs on Mycobacterium tuberculosis. Availability and Implementation: The method has been implemented in Java. It can be obtained from http://ls11-www.cs.tu-dortmund.de/people/marschal/paa_md/ Contact: tobias.marschall@tu-dortmund.de; sven.rahmann@tu-dortmund.de PMID:19478010

Marschall, Tobias; Rahmann, Sven

2009-01-01

396

Discovery Channel: Earth News  

NSDL National Science Digital Library

This Discovery Channel website features a large assortment of fascinating information about the physical environment of the earth. The website's live cam shows images of Mexico's Popocatepetl, one the most active volcanoes. Visitors can observe the big craters created on the earth by past meteors while students can create their own earthquake. And, users can find daily pictures and journal writings from a team of Mt. Everest climbers. With so many online earth adventures and activities, everyone should visit this fun and exciting website.

397

Discovery by the examiner  

SciTech Connect

The Manual of Patent Examining Procedure (M.P.E.P.), 4th Edition now has a chapter 2100 on patentability. At present this chapter only contains sections dealing with Patentable Subject Matter - Microorganisms and the Statutory Bars of Public Use and On Sale (35 U.S.C. 102(b), but it is the intent of the Patent and Trademark Office to expand its content as future revisions of the M.P.E.P. are issued. The requirement for information provisions of chapter 2100 - if they are upheld on judicial review - portend a significant change in the relationship of the examiner and the applicant in ex parte prosecution. In view of the fact that the Office positions which appear to herald this change have been adopted without public review or comment, it is imperative that members of the patent bar review them critically and express their concerns to the Office. Simply put, although the M.P.E.P. carefully avoids any use of the term, the Office in chapter 2100 is indicating that an examiner has a right of discovery in ex parte prosecution. Accordingly, the purpose of this article is to discuss the extent to which the Office is attempting to sanction discovery by examiners. In particular, it will explore certain of the ramifications of the requirement for information provisions of chapter 2100. It will begin by outlining the requirements for information in ex parte prosecution which are expressly permitted by the rules of practice. It will then review the authority for discovery requirements in ex parte prosecution and consider the sanction for failure to meet such a requirement. Some consideration will then be given to the extent and effect of a requirement for information presented under the aegis of chapter 2100. The potential for Office discovery in the prosecution of reissue applications will be briefly examined. Finally, the failure of the Office to seek public review or comment in presenting the requirement for information provisions of chapter 2100 will be briefly discussed.

Walterscheid, E.C.

1981-01-01

398

Discovery Channel - Mars  

NSDL National Science Digital Library

This Discovery Channel website furnishes news articles and interactive modules about the latest information on the NASA mission to Mars and the rovers. Using Macromedia Flash Player, students can explore the equipment on the rover, view videos of the rover landing on Mars, and examine panoramas of Mars. The stereo images of the Martian landscape are amazing, especially when viewed with 3D glasses. The website offers answers to the common questions related to NASA's mission. While many of the links on the side panel were not working at the time of this review, the same headings are presented within the main part of the website and function properly.

399

Physical activity correlates with glutamate receptor gene expression in spinally-projecting RVLM neurons: A laser capture microdissection study.  

PubMed

Physical inactivity is an important risk factor in the development of cardiovascular disease. The rostral ventrolateral portion of the medulla (RVLM) is composed of heterogeneous populations of neurons that are involved in the regulation of the cardiovascular system. Because of functional heterogeneity, studying the changes in the gene expression of this specific population of neurons within the RVLM is challenging. In the present study, a fluorescent retrograde tracer was injected into the spinal cord to specifically label bulbospinal RVLM neurons in sedentary and active rats. Laser capture microdissection (LCM) was then employed to collect the fluorescently labeled neurons from sections encompassing the rostrocaudal extent of the RVLM. RNA extracted from the neurons was used in qRT-PCR analysis. Changes in gene expression levels of glutamate and GABA receptor subunits were compared between sedentary and physically active rats. GLUR3 subunit showed a significant negative correlation between total running distance and its relative gene expression in active rats. There were no significant difference in the gene expression of NMDA (NR1, NR2A, NR2B, NR2C and NR2D), AMPA (GLUR1, GLUR2 and GLUR3) and GABAA (GABAA1 and GABAA2) receptor subunits. Overall, the present study demonstrates the feasibility of utilizing LCM to investigate the gene expression changes in a specific population of neurons in the RVLM. Correlation studies suggest that physical activity could contribute to neuroplasticity in the RVLM. PMID:25173073

Subramanian, Madhan; Holt, Avril G; Mueller, Patrick J

2014-10-17

400

Development Status of the WetLab-2 Project: New Tools for On-orbit Real-time Quantitative Gene Expression.  

NASA Technical Reports Server (NTRS)

The primary objective of NASA Ames Research Centers WetLab-2 Project is to place on the ISS a research platform to facilitate gene expression analysis via quantitative real-time PCR (qRT-PCR) of biological specimens grown or cultured on orbit. The WetLab-2 equipment will be capable of processing multiple sample types ranging from microbial cultures to animal tissues dissected on-orbit. In addition to the logistical benefits of in-situ sample processing and analysis, conducting qRT-PCR on-orbit eliminates the confounding effects on gene expression of reentry stresses and shock acting on live cells and organisms. The system can also validate terrestrial analyses of samples returned from ISS by providing quantitative on-orbit gene expression benchmarking prior to sample return. The ability to get on orbit data will provide investigators with the opportunity to adjust experimental parameters for subsequent trials based on the real-time data analysis without need for sample return and re-flight. Finally, WetLab-2 can be used for analysis of air, surface, water, and clinical samples to monitor environmental contaminants and crew health. The verification flight of the instrument is scheduled to launch on SpaceX-5 in Aug. 2014.Progress to date: The WetLab-2 project completed a thorough study of commercially available qRT-PCR systems and performed a downselect based on both scientific and engineering requirements. The selected instrument, the Cepheid SmartCycler, has advantages including modular design (16 independent PCR modules), low power consumption, and rapid ramp times. The SmartCycler has multiplex capabilities, assaying up to four genes of interest in each of the 16 modules. The WetLab-2 team is currently working with Cepheid to modify the unit for housing within an EXPRESS rack locker on the ISS. This will enable the downlink of data to the ground and provide uplink capabilities for programming, commanding, monitoring, and instrument maintenance. The project is currently designing a module that will lyse the cells and extract RNA of sufficient quality for use in qRT-PCR reactions while using a housekeeping gene to normalize RNA concentration and integrity. Current testing focuses on two promising commercial products and chemistries that allow for RNA extraction with minimal complexity and crew time.

Jung, Jimmy; Parra, Macarena P.; Almeida, Eduardo; Boone, Travis; Chinn, Tori; Ricco, Antonio; Souza, Kenneth; Hyde, Liz; Rukhsana, Yousuf; Richey, C. Scott

2013-01-01

401

Conquering cancer through discovery research.  

PubMed

Cancer is a leading cause of death worldwide. Cancer research improves our understanding of cancer biology, which leads to the discoveries of novel detection approaches and effective therapies for cancer. Translational cancer medicine changes essential science breakthroughs to the practice of medicine and uses clinical result to supply back into basic research. This article covers some studies in the field of translational cancer medicine including the identification of 319 driver genes and the 12 core cancer pathways, the use of MammaPrint in breast cancer, the development of OncoMap, the progress in genome-wide association studies, as well as the generation of microRNA networks in cancer and leukemia. Apart from cancer genome, cancer stem cells, immune and tumor microenvironment are also discussed. In addition, some innovations in translational cancer medicine are introduced. A number of targeted agents have been developed, such as the histone deacetylases inhibitors, poly(ADP-ribose) polymerase inhibitors, anti-mammalian target of rapamycin agents, and PI3K pathway inhibitors. There are also reports of the results from some important clinical trials, including the STAR P-2 trial, NeoBIG program, and BATTLE trial. This review focuses on discussions that emphasize the marriage between curiosity-driven basic research and patient care-focused clinical investigations. With highlights on the most up-to-date molecular, cellular, clinical, and therapeutic cancer research findings, this article tends to provide a wealth of insights into better understanding of the complexity of cancer. PMID:20882644

Cho, William C S

2010-09-01

402

STS-82 Discovery Launch  

NASA Technical Reports Server (NTRS)

The Space Shuttle Discovery cuts a bright swath through the early-morning darkness as it lifts off from Launch Pad 39A on a scheduled 10-day flight to service the Hubble Space Telescope (HST). Liftoff of Mission STS-82 occurred on-time at 3:55:17 a.m. EST, Feb. 11, 1997. Leading the veteran crew is Mission Commander Kenneth D. Bowersox. Scott J. 'Doc' Horowitz is the pilot. Mark C. Lee is the payload commander. Rounding out the seven-member crew are Mission Specialists Steven L. Smith, Gregory J. Harbaugh, Joseph R. 'Joe' Tanner and Steven A. Hawley. Four of the astronauts will be divided into two teams to perform the scheduled four back-to-back extravehicular activities (EVAs) or spacewalks. Lee and Smith will team up for EVAs 1 and 3 on flight days 4 and 6; Harbaugh and Tanner will perform EVAs 2 and 4 on flight days 5 and 7. Among the tasks will be to replace two outdated scientific instruments with two new instruments the Space Telescope Imaging Spectrograph (STIS) and the Near Infrared Camera and Multi-Object Spectrometer (NICMOS). This is the second servicing mission for HST, which was originally deployed in 1990 and designed to be serviced on-orbit about every three years. Hubble was first serviced in 1993. STS-82 is the second of eight planned flights in 1997. It is the 22nd flight of Discovery and the 82nd Shuttle mission.

1997-01-01

403

Discovery Channel: Teaching Tools  

NSDL National Science Digital Library

The Discovery Channel has compiled this collection of teaching tools to use in Arts, Math, Business/Careers, Science, English, Social Studies, Health, Technology, and Language instruction. For example, several worksheets on Algebra, Geometry and math vocabulary are posted online and include a link to a solution page. Teachers can take the worksheets posted as samples and use the online form to create a custom worksheet. Similarly, the puzzles and quizzes can also be custom designed to suit particular instructional goals. Those who complete the free online registration form can use the Discovery Channels Custom Classroom tool to save worksheets, quizzes or puzzles in a personal account. A Clip Art Gallery makes it easy and free to spice up classroom materials. Some sections, such as the discussion forum, require registration. The site notes that it is regularly reviewed by practicing classroom teachers in elementary school, middle school, and high school to ensure the material is relevant. Advertising on the website is minimal and its producers say they are working on adding more tools.

2007-06-08

404

Network discovery with DCM  

PubMed Central

This paper is about inferring or discovering the functional architecture of distributed systems using Dynamic Causal Modelling (DCM). We describe a scheme that recovers the (dynamic) Bayesian dependency graph (connections in a network) using observed network activity. This network discovery uses Bayesian model selection to identify the sparsity structure (absence of edges or connections) in a graph that best explains observed time-series. The implicit adjacency matrix specifies the form of the network (e.g., cyclic or acyclic) and its graph-theoretical attributes (e.g., degree distribution). The scheme is illustrated using functional magnetic resonance imaging (fMRI) time series to discover functional brain networks. Crucially, it can be applied to experimentally evoked responses (activation studies) or endogenous activity in task-free (resting state) fMRI studies. Unlike conventional approaches to network discovery, DCM permits the analysis of directed and cyclic graphs. Furthermore, it eschews (implausible) Markovian assumptions about the serial independence of random fluctuations. The scheme furnishes a network description of distributed activity in the brain that is optimal in the sense of having the greatest conditional probability, relative to other networks. The networks are characterised in terms of their connectivity or adjacency matrices and conditional distributions over the directed (and reciprocal) effective connectivity between connected nodes or regions. We envisage that this approach will provide a useful complement to current analyses of functional connectivity for both activation and resting-state studies. PMID:21182971

Friston, Karl J.; Li, Baojuan; Daunizeau, Jean; Stephan, Klaas E.

2011-01-01

405

K-Optimal Rule Discovery  

Microsoft Academic Search

K-optimal rule discovery finds the k rules that optimize a user-specified measure of rule value with respect to a set of sample data and user-specified con- straints. This approach avoids many limitations of the frequent itemset approach of association rule discovery. This paper presents a scalable algorithm applicable to a wide range of k-optimal rule discovery tasks and demonstrates its

Geoffrey I. Webb; Songmao Zhang

2005-01-01

406

Discovery Planetary Mission Operations Concepts  

NASA Technical Reports Server (NTRS)

The NASA Discovery Program of small planetary missions will provide opportunities to continue scientific exploration of the solar system in today's cost-constrained environment. Using a multidisciplinary team, JPL has developed plans to provide mission operations within the financial parameters established by the Discovery Program. This paper describes experiences and methods that show promise of allowing the Discovery Missions to operate within the program cost constraints while maintaining low mission risk, high data quality, and reponsive operations.

Coffin, R.

1994-01-01

407

Investigating transcriptional regulation: From analysis of complex networks to discovery of cis-regulatory elements  

E-print Network

Investigating transcriptional regulation: From analysis of complex networks to discovery of cis: Accepted 18 April 2009 Available online xxxx Keywords: Transcriptional regulatory network Co-regulation network Network motif Regulatory motif Motif discovery a b s t r a c t Regulation of gene expression

Babu, M. Madan

408

Hubble: 20 Years of Discovery  

NASA Video Gallery

Hubble's discoveries have revolutionized nearly all areas of current astronomical research from planetary science to cosmology. Actor and writer Brent Spiner narrates a visual journey back in time ...

409

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project.  

PubMed

There is substantial inter-individual variation in response to antidepressants, and genetic variation may, in part, explain these differences. For example, there is evidence to suggest that variation in the serotonin transporter gene (SLC6A4) predicts response to selective serotonin reuptake inhibitors (SSRIs). Environmental factors such as the occurrence of stressful life events before treatment may also be important. One prior report suggests that both factors interact in predicting response to antidepressants. GENDEP, a prospective part-randomized pharmacogenomics trial, collected longitudinal data on the outcome of 811 patients with major depression undergoing treatment with either an SSRI (escitalopram) or a tricyclic antidepressant (nortriptyline). Life events experienced over 6 months preceding treatment were measured using a List of Threatening Experiences Questionnaire, and several polymorphisms in the serotonin transporter gene (SLC6A4) have been genotyped including the serotonin transporter-linked polymorphic region (5-HTTLPR). Stressful life events were shown to predict a significantly better response to escitalopram but had no effect on response to nortriptyline. Variation in the 5-HTTLPR and another polymorphism in the gene, STin4, significantly modified these effects. Gene-environment interactions including life events may therefore be important not only in the aetiology of depression, but also in predicting response to antidepressant medication. PMID:20212518

Keers, R; Uher, R; Huezo-Diaz, P; Smith, R; Jaffee, S; Rietschel, M; Henigsberg, N; Kozel, D; Mors, O; Maier, W; Zobel, A; Hauser, J; Souery, D; Placentino, A; Larsen, E R; Dmitrzak-Weglarz, M; Gupta, B; Hoda, F; Craig, I; McGuffin, P; Farmer, A E; Aitchison, K J

2011-04-01

410

A generalized false discovery rate in microarray studies  

Microsoft Academic Search

The problem of identifying differentially expressed genes is considered in a microarray experiment. This motivates us to involve an appropriate multiple testing setup to high dimensional and low sample size testing problems in highly nonstandard setups. Family-wise error rate (FWER) is too conservative to control the type I error, whereas a less conservative false discovery rate has received considerable attention

Moonsu Kang; Heuiju Chun

2011-01-01

411

The Next Step: 25 Discoveries That Could Change Our Lives.  

ERIC Educational Resources Information Center

Describes (in separate articles) 25 developments in science, technology, and medicine that have potential impact on the near future. They include discoveries related to space butterflies, drugs, twenty-first century software, experimental mathematics, brain drugs, egg development, ultrasmall microchips, the biology of birth, cancer-causing genes,…

Science85, 1985

1985-01-01

412

Evolutionary computation for discovery of composite transcription factor binding sites  

Microsoft Academic Search

Previous research demonstrated the use of evolu- tionary computation for the discovery of transcrip- tion factor binding sites (TFBS)