• Title/Summary/Keyword: The Wellcome Trust

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Adult stem cell lineage tracing and deep tissue imaging

  • Fink, Juergen;Andersson-Rolf, Amanda;Koo, Bon-Kyoung
    • BMB Reports
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    • v.48 no.12
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    • pp.655-667
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    • 2015
  • Lineage tracing is a widely used method for understanding cellular dynamics in multicellular organisms during processes such as development, adult tissue maintenance, injury repair and tumorigenesis. Advances in tracing or tracking methods, from light microscopy-based live cell tracking to fluorescent label-tracing with two-photon microscopy, together with emerging tissue clearing strategies and intravital imaging approaches have enabled scientists to decipher adult stem and progenitor cell properties in various tissues and in a wide variety of biological processes. Although technical advances have enabled time-controlled genetic labeling and simultaneous live imaging, a number of obstacles still need to be overcome. In this review, we aim to provide an in-depth description of the traditional use of lineage tracing as well as current strategies and upcoming new methods of labeling and imaging.

Sirtuin/Sir2 Phylogeny, Evolutionary Considerations and Structural Conservation

  • Greiss, Sebastian;Gartner, Anton
    • Molecules and Cells
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    • v.28 no.5
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    • pp.407-415
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    • 2009
  • The sirtuins are a protein family named after the first identified member, S. cerevisiae Sir2p. Sirtuins are protein deacetylases whose activity is dependent on $NAD^+$ as a cosubstrate. They are structurally defined by two central domains that together form a highly conserved catalytic center, which catalyzes the transfer of an acetyl moiety from acetyllysine to $NAD^+$, yielding nicotinamide, the unique metabolite O-acetyl-ADP-ribose and deacetylated lysine. One or more sirtuins are present in virtually all species from bacteria to mammals. Here we describe a phylogenetic analysis of sirtuins. Based on their phylogenetic relationship, sirtuins can be grouped into over a dozen classes and subclasses. Humans, like most vertebrates, have seven sirtuins: SIRT1-SIRT7. These function in diverse cellular pathways, regulating transcriptional repression, aging, metabolism, DNA damage responses and apoptosis. We show that these seven sirtuins arose early during animal evolution. Conserved residues cluster around the catalytic center of known sirtuin family members.

Analysis of differences in human leukocyte antigen between the two Wellcome Trust Case Control Consortium control datasets

  • Jang, Chloe Soohyun;Choi, Wanson;Cook, Seungho;Han, Buhm
    • Genomics & Informatics
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    • v.17 no.3
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    • pp.29.1-29.8
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    • 2019
  • The Wellcome Trust Case Control Consortium (WTCCC) study was a large genome-wide association study that aimed to identify common variants associated with seven diseases. That study combined two control datasets (58C and UK Blood Services) as shared controls. Prior to using the combined controls, the WTCCC performed analyses to show that the genomic content of the control datasets was not significantly different. Recently, the analysis of human leukocyte antigen (HLA) genes has become prevalent due to the development of HLA imputation technology. In this project, we extended the between-control homogeneity analysis of the WTCCC to HLA. We imputed HLA information in the WTCCC control dataset and showed that the HLA content was not significantly different between the two control datasets, suggesting that the combined controls can be used as controls for HLA fine-mapping analysis based on HLA imputation.

Gramene database: A resource for comparative plant genomics, pathways and phylogenomics analyses

  • Tello-Ruiz, Marcela K.;Stein, Joshua;Wei, Sharon;Preece, Justin;Naithani, Sushma;Olson, Andrew;Jiao, Yinping;Gupta, Parul;Kumari, Sunita;Chougule, Kapeel;Elser, Justin;Wang, Bo;Thomason, James;Zhang, Lifang;D'Eustachio, Peter;Petryszak, Robert;Kersey, Paul;Lee, PanYoung Koung;Jaiswal, kaj;Ware, Doreen
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.135-135
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    • 2017
  • The Gramene database (http://www.gramene.org) is a powerful online resource for agricultural researchers, plant breeders and educators that provides easy access to reference data, visualizations and analytical tools for conducting cross-species comparisons. Learn the benefits of using Gramene to enrich your lectures, accelerate your research goals, and respond to your organismal community needs. Gramene's genomes portal hosts browsers for 44 complete reference genomes, including crops and model organisms, each displaying functional annotations, gene-trees with orthologous and paralogous gene classification, and whole-genome alignments. SNP and structural diversity data, available for 11 species, are displayed in the context of gene annotation, protein domains and functional consequences on transcript structure (e.g., missense variant). Browsers from multiple species can be viewed simultaneously with links to community-driven organismal databases. Thus, while hosting the underlying data for comparative studies, the portal also provides unified access to diverse plant community resources, and the ability for communities to upload and display private data sets in multiple standard formats. Our BioMart data mining interface enable complex queries and bulk download of sequence, annotation, homology and variation data. Gramene's pathway portal, the Plant Reactome, hosts over 240 pathways curated in rice and inferred in 66 additional plant species by orthology projection. Users may compare pathways across species, query and visualize curated expression data from EMBL-EBI's Expression Atlas in the context of pathways, analyze genome-scale expression data, and conduct pathway enrichment analysis. Our integrated search database and modern user interface leverage these diverse annotations to facilitate finding genes through selecting auto-suggested filters with interactive views of the results.

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Comparison of Two Meta-Analysis Methods: Inverse-Variance-Weighted Average and Weighted Sum of Z-Scores

  • Lee, Cue Hyunkyu;Cook, Seungho;Lee, Ji Sung;Han, Buhm
    • Genomics & Informatics
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    • v.14 no.4
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    • pp.173-180
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    • 2016
  • The meta-analysis has become a widely used tool for many applications in bioinformatics, including genome-wide association studies. A commonly used approach for meta-analysis is the fixed effects model approach, for which there are two popular methods: the inverse variance-weighted average method and weighted sum of z-scores method. Although previous studies have shown that the two methods perform similarly, their characteristics and their relationship have not been thoroughly investigated. In this paper, we investigate the optimal characteristics of the two methods and show the connection between the two methods. We demonstrate that the each method is optimized for a unique goal, which gives us insight into the optimal weights for the weighted sum of z-scores method. We examine the connection between the two methods both analytically and empirically and show that their resulting statistics become equivalent under certain assumptions. Finally, we apply both methods to the Wellcome Trust Case Control Consortium data and demonstrate that the two methods can give distinct results in certain study designs.

Inference of Aspergillus fumigatus Pathways by Computational Genome Analysis: Tricarboxylic Acid Cycle (TCA) and Glyoxylate Shunt

  • Do, Jin-Hwan;Anderson, Michael-J.;Denning, David-W.;Erich, Bornberg-Bauer
    • Journal of Microbiology and Biotechnology
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    • v.14 no.1
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    • pp.74-80
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    • 2004
  • Aspergillus fumigatus is one of the most common fungi in the human environment, both in-doors and out-doors. It is the main causative agent of invasive aspergillosis, a life-threatening mycosis among immunocompromised patients. The genome has been sequenced by an international consortium, including the Wellcome Trust Sanger Institute (U.K.) and The Institute for Genomic Research (TIGR, U.S.A.), and a ten times whole genome shotgun sequence assembly has been made publicly available. In this study, we identified tricarboxylic acid (TCA) cycle enzymes of A. fumigatus by comparative analysis with four other fungal species. The open reading frames showed high amino acid sequence similarity with the other fungal citric acid enzymes and well-conserved functional domains. All genes present in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans, and Neurospora crassa were also found in A. fumigatus. In addition, we identified four A. fumigatus genes coding for enzymes in the glyoxylate shunt, which may be required for fungal virulence. The architecture of multi-gene encoded enzymes, such as isocitrate dehydrogenase, 2-ketoglutarate, succinyl-CoA synthetase, and succinate dehydrogenase was well conserved in A. fumigatus. Furthermore, our results show that genes of A. fumigatus can be detected reliably using GlimmerM.

Analysis on the Open Access Policies, Publishing, and Archiving in the Field of Medicine (의학 분야 오픈 액세스 현황 분석을 통한 국내 의학 정보 활성화 방안)

  • Joung Kyoung-Hee
    • Journal of the Korean Society for Library and Information Science
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    • v.40 no.2
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    • pp.389-414
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    • 2006
  • This paper analyzes the current status of open access policies, publishing, and archiving in the field of medicine. Journals indexed in SCI are published by open access publishers such as BMC Ltd. and PLoS and then the research articles in those journals are archived in PMC and BMC. Also, funding institutions participate in developing open access as a new scholarly communication model and governments or independent funding institutions outside the country make policies for open access. But scholary communities in Korea do not develop their services in the level of a new scholarly communication model even though they open their journal articles on the homepages. This paper suggests several plans for the open access scholarly communication in the field of medicine in Korea.

UNDERSTANDING OF EPIGENETICS AND DNA METHYLATION (인간 게놈의 Copy Number Variation과 유전자 질환)

  • Oh, Jung-Hwan;Nishimura, Ichiro
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.2
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    • pp.205-212
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    • 2008
  • Genetic variation in the human genome occurs on various levels; from the single nucleotide polymorphism to large, microscopically visible chromosome anomalies. It can be present in many forms, including variable number of tandem repeat (VNTRs; e.g., mini- and microsatellites), presence/absence of transposable elements (e.g., Alu elements), single nucleotide polymorphisms, and structural alterations (e.g., copy number variation, segmental duplication, inversion, translocation). Until recently SNPs were thought to be the main source of genetic and phenotypic human variation. However, the use of methods such as array comparative genomic hybridization (array CGH) and fluorescence in situ hybridization (FISH) have revealed the presence of copy number variations(CNVs) ranging from kilobases (kb) to megabases (Mb) in the human genome. There is great interest in the possibility that CNVs playa role in the etiology of common disease such as HIV-1/AIDS, diabetes, autoimmune disease, heart disease and cancer. The discovery of widespread copy number variation in human provides insights into genetic variability among populations and provides a foundation for studies of the contribution of CNVs to evolution and disease.