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      • Launching the C-HPP neXt-CP50 Pilot Project for Functional Characterization of Identified Proteins with No Known Function

        Paik, Young-Ki,Lane, Lydie,Kawamura, Takeshi,Chen, Yu-Ju,Cho, Je-Yoel,LaBaer, Joshua,Yoo, Jong Shin,Domont, Gilberto,Corrales, Fernando,Omenn, Gilbert S.,Archakov, Alexander,Encarnació,n-Guevara American Chemical Society 2018 JOURNAL OF PROTEOME RESEARCH Vol.17 No.12

        <P>An important goal of the Human Proteome Organization (HUPO) Chromosome-centric Human Proteome Project (C-HPP) is to correctly define the number of canonical proteins encoded by their cognate open reading frames on each chromosome in the human genome. When identified with high confidence of protein evidence (PE), such proteins are termed PE1 proteins in the online database resource, neXtProt. However, proteins that have not been identified unequivocally at the protein level but that have other evidence suggestive of their existence (PE2-4) are termed missing proteins (MPs). The number of MPs has been reduced from 5511 in 2012 to 2186 in 2018 (neXtProt 2018-01-17 release). Although the annotation of the human proteome has made significant progress, the “parts list” alone does not inform function. Indeed, 1937 proteins representing ∼10% of the human proteome have no function either annotated from experimental characterization or predicted by homology to other proteins. Specifically, these 1937 “dark proteins” of the so-called dark proteome are composed of 1260 functionally uncharacterized but identified PE1 proteins, designated as uPE1, plus 677 MPs from categories PE2-PE4, which also have no known or predicted function and are termed uMPs. At the HUPO-2017 Annual Meeting, the C-HPP officially adopted the uPE1 pilot initiative, with 14 participating international teams later committing to demonstrate the feasibility of the functional <U>c</U>haracterization of large numbers of dark <U>p</U>roteins (CP), starting first with 50 uPE1 proteins, in a stepwise chromosome-centric organizational manner. The second aim of the feasibility phase to <U>c</U>haracterize protein (CP) functions of 50 uPE1 proteins, termed the neXt-CP50 initiative, is to utilize a variety of approaches and workflows according to individual team expertise, interest, and resources so as to enable the C-HPP to recommend experimentally proven workflows to the proteome community within 3 years. The results from this pilot will not only be the cornerstone of a larger characterization initiative but also enhance understanding of the human proteome and integrated cellular networks for the discovery of new mechanisms of pathology, mechanistically informative biomarkers, and rational drug targets.</P> [FIG OMISSION]</BR>

      • Quest for Missing Proteins: Update 2015 on Chromosome-Centric Human Proteome Project

        Horvatovich, Pé,ter,Lundberg, Emma K.,Chen, Yu-Ju,Sung, Ting-Yi,He, Fuchu,Nice, Edouard C.,Goode, Robert J.,Yu, Simon,Ranganathan, Shoba,Baker, Mark S.,Domont, Gilberto B.,Velasquez, Erika,Li, D American Chemical Society 2015 Journal of Proteome Research Vol.14 No.9

        <P>This paper summarizes the recent activities of the Chromosome-Centric Human Proteome Project (C-HPP) consortium, which develops new technologies to identify yet-to-be annotated proteins (termed “missing proteins”) in biological samples that lack sufficient experimental evidence at the protein level for confident protein identification. The C-HPP also aims to identify new protein forms that may be caused by genetic variability, post-translational modifications, and alternative splicing. Proteogenomic data integration forms the basis of the C-HPP’s activities; therefore, we have summarized some of the key approaches and their roles in the project. We present new analytical technologies that improve the chemical space and lower detection limits coupled to bioinformatics tools and some publicly available resources that can be used to improve data analysis or support the development of analytical assays. Most of this paper’s content has been compiled from posters, slides, and discussions presented in the series of C-HPP workshops held during 2014. All data (posters, presentations) used are available at the C-HPP Wiki (<uri xlink:href='http://c-hpp.webhosting.rug.nl/' xlink:type='simple'>http://c-hpp.webhosting.rug.nl/</uri>) and in the Supporting Information.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jprobs/2015/jprobs.2015.14.issue-9/pr5013009/production/images/medium/pr-2014-013009_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/pr5013009'>ACS Electronic Supporting Info</A></P>

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