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  • 1
    Publication Date: 2011-09-13
    Description: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (〉/=140 mm Hg systolic blood pressure or 〉/=90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340926/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340926/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Consortium for Blood Pressure Genome-Wide Association Studies -- Ehret, Georg B -- Munroe, Patricia B -- Rice, Kenneth M -- Bochud, Murielle -- Johnson, Andrew D -- Chasman, Daniel I -- Smith, Albert V -- Tobin, Martin D -- Verwoert, Germaine C -- Hwang, Shih-Jen -- Pihur, Vasyl -- Vollenweider, Peter -- O'Reilly, Paul F -- Amin, Najaf -- Bragg-Gresham, Jennifer L -- Teumer, Alexander -- Glazer, Nicole L -- Launer, Lenore -- Zhao, Jing Hua -- Aulchenko, Yurii -- Heath, Simon -- Sober, Siim -- Parsa, Afshin -- Luan, Jian'an -- Arora, Pankaj -- Dehghan, Abbas -- Zhang, Feng -- Lucas, Gavin -- Hicks, Andrew A -- Jackson, Anne U -- Peden, John F -- Tanaka, Toshiko -- Wild, Sarah H -- Rudan, Igor -- Igl, Wilmar -- Milaneschi, Yuri -- Parker, Alex N -- Fava, Cristiano -- Chambers, John C -- Fox, Ervin R -- Kumari, Meena -- Go, Min Jin -- van der Harst, Pim -- Kao, Wen Hong Linda -- Sjogren, Marketa -- Vinay, D G -- Alexander, Myriam -- Tabara, Yasuharu -- Shaw-Hawkins, Sue -- Whincup, Peter H -- Liu, Yongmei -- Shi, Gang -- Kuusisto, Johanna -- Tayo, Bamidele -- Seielstad, Mark -- Sim, Xueling -- Nguyen, Khanh-Dung Hoang -- Lehtimaki, Terho -- Matullo, Giuseppe -- Wu, Ying -- Gaunt, Tom R -- Onland-Moret, N Charlotte -- Cooper, Matthew N -- Platou, Carl G P -- Org, Elin -- Hardy, Rebecca -- Dahgam, Santosh -- Palmen, Jutta -- Vitart, Veronique -- Braund, Peter S -- Kuznetsova, Tatiana -- Uiterwaal, Cuno S P M -- Adeyemo, Adebowale -- Palmas, Walter -- Campbell, Harry -- Ludwig, Barbara -- Tomaszewski, Maciej -- Tzoulaki, Ioanna -- Palmer, Nicholette D -- CARDIoGRAM consortium -- CKDGen Consortium -- KidneyGen Consortium -- EchoGen consortium -- CHARGE-HF consortium -- Aspelund, Thor -- Garcia, Melissa -- Chang, Yen-Pei C -- O'Connell, Jeffrey R -- Steinle, Nanette I -- Grobbee, Diederick E -- Arking, Dan E -- Kardia, Sharon L -- Morrison, Alanna C -- Hernandez, Dena -- Najjar, Samer -- McArdle, Wendy L -- Hadley, David -- Brown, Morris J -- Connell, John M -- Hingorani, Aroon D -- Day, Ian N M -- Lawlor, Debbie A -- Beilby, John P -- Lawrence, Robert W -- Clarke, Robert -- Hopewell, Jemma C -- Ongen, Halit -- Dreisbach, Albert W -- Li, Yali -- Young, J Hunter -- Bis, Joshua C -- Kahonen, Mika -- Viikari, Jorma -- Adair, Linda S -- Lee, Nanette R -- Chen, Ming-Huei -- Olden, Matthias -- Pattaro, Cristian -- Bolton, Judith A Hoffman -- Kottgen, Anna -- Bergmann, Sven -- Mooser, Vincent -- Chaturvedi, Nish -- Frayling, Timothy M -- Islam, Muhammad -- Jafar, Tazeen H -- Erdmann, Jeanette -- Kulkarni, Smita R -- Bornstein, Stefan R -- Grassler, Jurgen -- Groop, Leif -- Voight, Benjamin F -- Kettunen, Johannes -- Howard, Philip -- Taylor, Andrew -- Guarrera, Simonetta -- Ricceri, Fulvio -- Emilsson, Valur -- Plump, Andrew -- Barroso, Ines -- Khaw, Kay-Tee -- Weder, Alan B -- Hunt, Steven C -- Sun, Yan V -- Bergman, Richard N -- Collins, Francis S -- Bonnycastle, Lori L -- Scott, Laura J -- Stringham, Heather M -- Peltonen, Leena -- Perola, Markus -- Vartiainen, Erkki -- Brand, Stefan-Martin -- Staessen, Jan A -- Wang, Thomas J -- Burton, Paul R -- Soler Artigas, Maria -- Dong, Yanbin -- Snieder, Harold -- Wang, Xiaoling -- Zhu, Haidong -- Lohman, Kurt K -- Rudock, Megan E -- Heckbert, Susan R -- Smith, Nicholas L -- Wiggins, Kerri L -- Doumatey, Ayo -- Shriner, Daniel -- Veldre, Gudrun -- Viigimaa, Margus -- Kinra, Sanjay -- Prabhakaran, Dorairaj -- Tripathy, Vikal -- Langefeld, Carl D -- Rosengren, Annika -- Thelle, Dag S -- Corsi, Anna Maria -- Singleton, Andrew -- Forrester, Terrence -- Hilton, Gina -- McKenzie, Colin A -- Salako, Tunde -- Iwai, Naoharu -- Kita, Yoshikuni -- Ogihara, Toshio -- Ohkubo, Takayoshi -- Okamura, Tomonori -- Ueshima, Hirotsugu -- Umemura, Satoshi -- Eyheramendy, Susana -- Meitinger, Thomas -- Wichmann, H-Erich -- Cho, Yoon Shin -- Kim, Hyung-Lae -- Lee, Jong-Young -- Scott, James -- Sehmi, Joban S -- Zhang, Weihua -- Hedblad, Bo -- Nilsson, Peter -- Smith, George Davey -- Wong, Andrew -- Narisu, Narisu -- Stancakova, Alena -- Raffel, Leslie J -- Yao, Jie -- Kathiresan, Sekar -- O'Donnell, Christopher J -- Schwartz, Stephen M -- Ikram, M Arfan -- Longstreth, W T Jr -- Mosley, Thomas H -- Seshadri, Sudha -- Shrine, Nick R G -- Wain, Louise V -- Morken, Mario A -- Swift, Amy J -- Laitinen, Jaana -- Prokopenko, Inga -- Zitting, Paavo -- Cooper, Jackie A -- Humphries, Steve E -- Danesh, John -- Rasheed, Asif -- Goel, Anuj -- Hamsten, Anders -- Watkins, Hugh -- Bakker, Stephan J L -- van Gilst, Wiek H -- Janipalli, Charles S -- Mani, K Radha -- Yajnik, Chittaranjan S -- Hofman, Albert -- Mattace-Raso, Francesco U S -- Oostra, Ben A -- Demirkan, Ayse -- Isaacs, Aaron -- Rivadeneira, Fernando -- Lakatta, Edward G -- Orru, Marco -- Scuteri, Angelo -- Ala-Korpela, Mika -- Kangas, Antti J -- Lyytikainen, Leo-Pekka -- Soininen, Pasi -- Tukiainen, Taru -- Wurtz, Peter -- Ong, Rick Twee-Hee -- Dorr, Marcus -- Kroemer, Heyo K -- Volker, Uwe -- Volzke, Henry -- Galan, Pilar -- Hercberg, Serge -- Lathrop, Mark -- Zelenika, Diana -- Deloukas, Panos -- Mangino, Massimo -- Spector, Tim D -- Zhai, Guangju -- Meschia, James F -- Nalls, Michael A -- Sharma, Pankaj -- Terzic, Janos -- Kumar, M V Kranthi -- Denniff, Matthew -- Zukowska-Szczechowska, Ewa -- Wagenknecht, Lynne E -- Fowkes, F Gerald R -- Charchar, Fadi J -- Schwarz, Peter E H -- Hayward, Caroline -- Guo, Xiuqing -- Rotimi, Charles -- Bots, Michiel L -- Brand, Eva -- Samani, Nilesh J -- Polasek, Ozren -- Talmud, Philippa J -- Nyberg, Fredrik -- Kuh, Diana -- Laan, Maris -- Hveem, Kristian -- Palmer, Lyle J -- van der Schouw, Yvonne T -- Casas, Juan P -- Mohlke, Karen L -- Vineis, Paolo -- Raitakari, Olli -- Ganesh, Santhi K -- Wong, Tien Y -- Tai, E Shyong -- Cooper, Richard S -- Laakso, Markku -- Rao, Dabeeru C -- Harris, Tamara B -- Morris, Richard W -- Dominiczak, Anna F -- Kivimaki, Mika -- Marmot, Michael G -- Miki, Tetsuro -- Saleheen, Danish -- Chandak, Giriraj R -- Coresh, Josef -- Navis, Gerjan -- Salomaa, Veikko -- Han, Bok-Ghee -- Zhu, Xiaofeng -- Kooner, Jaspal S -- Melander, Olle -- Ridker, Paul M -- Bandinelli, Stefania -- Gyllensten, Ulf B -- Wright, Alan F -- Wilson, James F -- Ferrucci, Luigi -- Farrall, Martin -- Tuomilehto, Jaakko -- Pramstaller, Peter P -- Elosua, Roberto -- Soranzo, Nicole -- Sijbrands, Eric J G -- Altshuler, David -- Loos, Ruth J F -- Shuldiner, Alan R -- Gieger, Christian -- Meneton, Pierre -- Uitterlinden, Andre G -- Wareham, Nicholas J -- Gudnason, Vilmundur -- Rotter, Jerome I -- Rettig, Rainer -- Uda, Manuela -- Strachan, David P -- Witteman, Jacqueline C M -- Hartikainen, Anna-Liisa -- Beckmann, Jacques S -- Boerwinkle, Eric -- Vasan, Ramachandran S -- Boehnke, Michael -- Larson, Martin G -- Jarvelin, Marjo-Riitta -- Psaty, Bruce M -- Abecasis, Goncalo R -- Chakravarti, Aravinda -- Elliott, Paul -- van Duijn, Cornelia M -- Newton-Cheh, Christopher -- Levy, Daniel -- Caulfield, Mark J -- Johnson, Toby -- 068545/Z/02/Wellcome Trust/United Kingdom -- 070191/Z/03/Z/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 080747/Z/06/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 1R01AG032098-01A/AG/NIA NIH HHS/ -- 1RL1MH083268-01/MH/NIMH NIH HHS/ -- 263 MD 821336/MD/NIMHD NIH HHS/ -- 263 MD 9164/MD/NIMHD NIH HHS/ -- 263-MA-410953/PHS HHS/ -- 2M01RR010284/RR/NCRR NIH 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MOP172605/Canadian Institutes of Health Research/Canada -- MOP77682/Canadian Institutes of Health Research/Canada -- N01 HC-15103/HC/NHLBI NIH HHS/ -- N01 HC-55222/HC/NHLBI NIH HHS/ -- N01 HC-95159/HC/NHLBI NIH HHS/ -- N01 HC-95169/HC/NHLBI NIH HHS/ -- N01-AG-1-2109/AG/NIA NIH HHS/ -- N01-AG-12100/AG/NIA NIH HHS/ -- N01-HC-25195/HC/NHLBI NIH HHS/ -- N01-HC-35129/HC/NHLBI NIH HHS/ -- N01-HC-45133/HC/NHLBI NIH HHS/ -- N01-HC-55015/HC/NHLBI NIH HHS/ -- N01-HC-55016/HC/NHLBI NIH HHS/ -- N01-HC-55018/HC/NHLBI NIH HHS/ -- N01-HC-55019/HC/NHLBI NIH HHS/ -- N01-HC-55020/HC/NHLBI NIH HHS/ -- N01-HC-55021/HC/NHLBI NIH HHS/ -- N01-HC-55022/HC/NHLBI NIH HHS/ -- N01-HC-75150/HC/NHLBI NIH HHS/ -- N01-HC-85079/HC/NHLBI NIH HHS/ -- N01-HC-85080/HC/NHLBI NIH HHS/ -- N01-HC-85081/HC/NHLBI NIH HHS/ -- N01-HC-85082/HC/NHLBI NIH HHS/ -- N01-HC-85083/HC/NHLBI NIH HHS/ -- N01-HC-85084/HC/NHLBI NIH HHS/ -- N01-HC-85085/HC/NHLBI NIH HHS/ -- N01-HC-85086/HC/NHLBI NIH HHS/ -- N01-HC-95160/HC/NHLBI NIH HHS/ -- 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Foundation/United Kingdom -- RG/08/008/25291/British Heart Foundation/United Kingdom -- RG/08/013/25942/British Heart Foundation/United Kingdom -- RG/08/014/24067/British Heart Foundation/United Kingdom -- RG/98002/British Heart Foundation/United Kingdom -- RG08/01/British Heart Foundation/United Kingdom -- RR-024156/RR/NCRR NIH HHS/ -- RR20649/RR/NCRR NIH HHS/ -- S06GM008016-320107/GM/NIGMS NIH HHS/ -- S06GM008016-380111/GM/NIGMS NIH HHS/ -- SP/04/002/British Heart Foundation/United Kingdom -- SP/08/005/25115/British Heart Foundation/United Kingdom -- TW008288/TW/FIC NIH HHS/ -- TW05596/TW/FIC NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 GM074518-04/GM/NIGMS NIH HHS/ -- U01 HL054466/HL/NHLBI NIH HHS/ -- U01 HL054466-11/HL/NHLBI NIH HHS/ -- U01 HL054471/HL/NHLBI NIH HHS/ -- U01 HL054473/HL/NHLBI NIH HHS/ -- U01 HL054527/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 NS069208/NS/NINDS NIH HHS/ -- U01 NS069208-01/NS/NINDS NIH HHS/ -- U01DE018903/DE/NIDCR NIH HHS/ -- U01DE01899/DE/NIDCR NIH HHS/ -- U01HG004399/HG/NHGRI NIH HHS/ -- U01HG004402/HG/NHGRI NIH HHS/ -- U01HG004415/HG/NHGRI NIH HHS/ -- U01HG004422/HG/NHGRI NIH HHS/ -- U01HG004423/HG/NHGRI NIH HHS/ -- U01HG004436/HG/NHGRI NIH HHS/ -- U01HG004438/HG/NHGRI NIH HHS/ -- U01HG004446/HG/NHGRI NIH HHS/ -- U01HG004726/HG/NHGRI NIH HHS/ -- U01HG004728/HG/NHGRI NIH HHS/ -- U01HG004729/HG/NHGRI NIH HHS/ -- U01HG004735/HG/NHGRI NIH HHS/ -- U01HG004738/HG/NHGRI NIH HHS/ -- U10 HL054512/HL/NHLBI NIH HHS/ -- U10HL054512/HL/NHLBI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1RR025005/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2011 Sep 11;478(7367):103-9. doi: 10.1038/nature10405.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21909115" target="_blank"〉PubMed〈/a〉
    Keywords: Africa/ethnology ; Asia/ethnology ; Blood Pressure/*genetics/physiology ; Cardiovascular Diseases/*genetics ; Coronary Artery Disease/genetics ; Europe/ethnology ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study ; Humans ; Hypertension/genetics ; Kidney Diseases/genetics ; Polymorphism, Single Nucleotide/*genetics ; Stroke/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2015-09-10
    Description: Somaclonal variation arises in plants and animals when differentiated somatic cells are induced into a pluripotent state, but the resulting clones differ from each other and from their parents. In agriculture, somaclonal variation has hindered the micropropagation of elite hybrids and genetically modified crops, but the mechanism responsible remains unknown. The oil palm fruit 'mantled' abnormality is a somaclonal variant arising from tissue culture that drastically reduces yield, and has largely halted efforts to clone elite hybrids for oil production. Widely regarded as an epigenetic phenomenon, 'mantling' has defied explanation, but here we identify the MANTLED locus using epigenome-wide association studies of the African oil palm Elaeis guineensis. DNA hypomethylation of a LINE retrotransposon related to rice Karma, in the intron of the homeotic gene DEFICIENS, is common to all mantled clones and is associated with alternative splicing and premature termination. Dense methylation near the Karma splice site (termed the Good Karma epiallele) predicts normal fruit set, whereas hypomethylation (the Bad Karma epiallele) predicts homeotic transformation, parthenocarpy and marked loss of yield. Loss of Karma methylation and of small RNA in tissue culture contributes to the origin of mantled, while restoration in spontaneous revertants accounts for non-Mendelian inheritance. The ability to predict and cull mantling at the plantlet stage will facilitate the introduction of higher performing clones and optimize environmentally sensitive land resources.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ong-Abdullah, Meilina -- Ordway, Jared M -- Jiang, Nan -- Ooi, Siew-Eng -- Kok, Sau-Yee -- Sarpan, Norashikin -- Azimi, Nuraziyan -- Hashim, Ahmad Tarmizi -- Ishak, Zamzuri -- Rosli, Samsul Kamal -- Malike, Fadila Ahmad -- Bakar, Nor Azwani Abu -- Marjuni, Marhalil -- Abdullah, Norziha -- Yaakub, Zulkifli -- Amiruddin, Mohd Din -- Nookiah, Rajanaidu -- Singh, Rajinder -- Low, Eng-Ti Leslie -- Chan, Kuang-Lim -- Azizi, Norazah -- Smith, Steven W -- Bacher, Blaire -- Budiman, Muhammad A -- Van Brunt, Andrew -- Wischmeyer, Corey -- Beil, Melissa -- Hogan, Michael -- Lakey, Nathan -- Lim, Chin-Ching -- Arulandoo, Xaviar -- Wong, Choo-Kien -- Choo, Chin-Nee -- Wong, Wei-Chee -- Kwan, Yen-Yen -- Alwee, Sharifah Shahrul Rabiah Syed -- Sambanthamurthi, Ravigadevi -- Martienssen, Robert A -- R01 GM067014/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Sep 24;525(7570):533-7. doi: 10.1038/nature15365. Epub 2015 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Malaysian Palm Oil Board, 6, Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia. ; Orion Genomics, 4041 Forest Park Avenue, St Louis, Missouri 63108, USA. ; United Plantations Berhad, Jendarata Estate, 36009 Teluk Intan, Perak, Malaysia. ; Applied Agricultural Resources Sdn Bhd, No. 11, Jalan Teknologi 3/6, Taman Sains Selangor 1, 47810 Kota Damansara, Petaling Jaya, Selangor, Malaysia. ; FELDA Global Ventures R&D Sdn Bhd, c/o FELDA Biotechnology Centre, PT 23417, Lengkuk Teknologi, 71760 Bandar Enstek, Negeri Sembilan, Malaysia. ; Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26352475" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; Alternative Splicing/genetics ; Arecaceae/*genetics/metabolism ; *DNA Methylation ; Epigenesis, Genetic/*genetics ; *Epigenomics ; Fruit/genetics ; Genes, Homeobox/genetics ; Genetic Association Studies ; Genome, Plant/*genetics ; Introns/genetics ; Molecular Sequence Data ; *Phenotype ; Plant Oils/analysis/metabolism ; RNA Splice Sites/genetics ; RNA, Small Interfering/genetics ; Retroelements/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-11-12
    Description: In multicellular organisms, transcription regulation is one of the central mechanisms modelling lineage differentiation and cell-fate determination. Transcription requires dynamic chromatin configurations between promoters and their corresponding distal regulatory elements. It is believed that their communication occurs within large discrete foci of aggregated RNA polymerases termed transcription factories in three-dimensional nuclear space. However, the dynamic nature of chromatin connectivity has not been characterized at the genome-wide level. Here, through a chromatin interaction analysis with paired-end tagging approach using an antibody that primarily recognizes the pre-initiation complexes of RNA polymerase II, we explore the transcriptional interactomes of three mouse cells of progressive lineage commitment, including pluripotent embryonic stem cells, neural stem cells and neurosphere stem/progenitor cells. Our global chromatin connectivity maps reveal approximately 40,000 long-range interactions, suggest precise enhancer-promoter associations and delineate cell-type-specific chromatin structures. Analysis of the complex regulatory repertoire shows that there are extensive colocalizations among promoters and distal-acting enhancers. Most of the enhancers associate with promoters located beyond their nearest active genes, indicating that the linear juxtaposition is not the only guiding principle driving enhancer target selection. Although promoter-enhancer interactions exhibit high cell-type specificity, promoters involved in interactions are found to be generally common and mostly active among different cells. Chromatin connectivity networks reveal that the pivotal genes of reprogramming functions are transcribed within physical proximity to each other in embryonic stem cells, linking chromatin architecture to coordinated gene expression. Our study sets the stage for the full-scale dissection of spatial and temporal genome structures and their roles in orchestrating development.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954713/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954713/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Yubo -- Wong, Chee-Hong -- Birnbaum, Ramon Y -- Li, Guoliang -- Favaro, Rebecca -- Ngan, Chew Yee -- Lim, Joanne -- Tai, Eunice -- Poh, Huay Mei -- Wong, Eleanor -- Mulawadi, Fabianus Hendriyan -- Sung, Wing-Kin -- Nicolis, Silvia -- Ahituv, Nadav -- Ruan, Yijun -- Wei, Chia-Lin -- 1U54HG004557-01/HG/NHGRI NIH HHS/ -- GGP12152/Telethon/Italy -- GM61390/GM/NIGMS NIH HHS/ -- R01 DK090382/DK/NIDDK NIH HHS/ -- R01 HD059862/HD/NICHD NIH HHS/ -- R01 HG004456-01/HG/NHGRI NIH HHS/ -- R01 NS079231/NS/NINDS NIH HHS/ -- R01DK090382/DK/NIDDK NIH HHS/ -- R01HD059862/HD/NICHD NIH HHS/ -- R01HG003521-01/HG/NHGRI NIH HHS/ -- R01HG005058/HG/NHGRI NIH HHS/ -- R01HG006768/HG/NHGRI NIH HHS/ -- R01NS079231/NS/NINDS NIH HHS/ -- U01 GM061390/GM/NIGMS NIH HHS/ -- U19 GM061390/GM/NIGMS NIH HHS/ -- England -- Nature. 2013 Dec 12;504(7479):306-10. doi: 10.1038/nature12716. Epub 2013 Nov 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Sequencing Technology Group, Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, California 94598, USA [2] [3] Department of Life Sciences, Faculty of Natural Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel (R.Y.B.); National Heart, Lung, and Blood Institute, National Institutes of Health, Systems Biology Center, 9000 Rockville Pike, Bethesda, Maryland 20892, USA (Y.Z.). ; 1] Sequencing Technology Group, Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, California 94598, USA [2]. ; 1] Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, UCSF, San Francisco, California 94158, USA [2] [3] Department of Life Sciences, Faculty of Natural Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel (R.Y.B.); National Heart, Lung, and Blood Institute, National Institutes of Health, Systems Biology Center, 9000 Rockville Pike, Bethesda, Maryland 20892, USA (Y.Z.). ; 1] The Jackson Laboratory for Genomic Medicine, and Department of Genetic and Development Biology, University of Connecticut, 400 Farmington, Connecticut 06030, USA [2] Genome Institute of Singapore, 60 Biopolis Street, 138672 Singapore. ; Department of Biological Sciences and Biotechnology, University of Milano-Bicocca, 20126 Milano, Italy. ; Sequencing Technology Group, Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, California 94598, USA. ; Genome Institute of Singapore, 60 Biopolis Street, 138672 Singapore. ; Department of Bioengineering and Therapeutic Sciences, Institute for Human Genetics, UCSF, San Francisco, California 94158, USA. ; The Jackson Laboratory for Genomic Medicine, and Department of Genetic and Development Biology, University of Connecticut, 400 Farmington, Connecticut 06030, USA. ; 1] Sequencing Technology Group, Joint Genome Institute, Lawrence Berkeley National Laboratory, Walnut Creek, California 94598, USA [2] Genome Institute of Singapore, 60 Biopolis Street, 138672 Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24213634" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Lineage ; Chromatin/*genetics/*metabolism ; Embryonic Stem Cells/metabolism ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation/*genetics ; In Situ Hybridization, Fluorescence ; Mice ; Neural Stem Cells/metabolism ; Promoter Regions, Genetic/*genetics ; RNA Polymerase II/metabolism ; Transcription, Genetic/genetics ; Zebrafish/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2018-05-01
    Description: Picky comprehensively detects high-resolution structural variants in nanopore long reads Picky comprehensively detects high-resolution structural variants in nanopore long reads, Published online: 30 April 2018; doi:10.1038/s41592-018-0002-6 The computational pipeline Picky detects the full spectrum of structural variants and their breakpoints in long nanopore sequence reads.
    Print ISSN: 1548-7091
    Electronic ISSN: 1548-7105
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2013-01-29
    Description: Cellular reprogramming of somatic cells to patient-specific induced pluripotent stem cells (iPSCs) enables in vitro modelling of human genetic disorders for pathogenic investigations and therapeutic screens. However, using iPSC-derived cardiomyocytes (iPSC-CMs) to model an adult-onset heart disease remains challenging owing to the uncertainty regarding the ability of relatively immature iPSC-CMs to fully recapitulate adult disease phenotypes. Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart disease characterized by pathological fatty infiltration and cardiomyocyte loss predominantly in the right ventricle, which is associated with life-threatening ventricular arrhythmias. Over 50% of affected individuals have desmosome gene mutations, most commonly in PKP2, encoding plakophilin-2 (ref. 9). The median age at presentation of ARVD/C is 26 years. We used previously published methods to generate iPSC lines from fibroblasts of two patients with ARVD/C and PKP2 mutations. Mutant PKP2 iPSC-CMs demonstrate abnormal plakoglobin nuclear translocation and decreased beta-catenin activity in cardiogenic conditions; yet, these abnormal features are insufficient to reproduce the pathological phenotypes of ARVD/C in standard cardiogenic conditions. Here we show that induction of adult-like metabolic energetics from an embryonic/glycolytic state and abnormal peroxisome proliferator-activated receptor gamma (PPAR-gamma) activation underlie the pathogenesis of ARVD/C. By co-activating normal PPAR-alpha-dependent metabolism and abnormal PPAR-gamma pathway in beating embryoid bodies (EBs) with defined media, we established an efficient ARVD/C in vitro model within 2 months. This model manifests exaggerated lipogenesis and apoptosis in mutant PKP2 iPSC-CMs. iPSC-CMs with a homozygous PKP2 mutation also had calcium-handling deficits. Our study is the first to demonstrate that induction of adult-like metabolism has a critical role in establishing an adult-onset disease model using patient-specific iPSCs. Using this model, we revealed crucial pathogenic insights that metabolic derangement in adult-like metabolic milieu underlies ARVD/C pathologies, enabling us to propose novel disease-modifying therapeutic strategies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753229/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753229/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Changsung -- Wong, Johnson -- Wen, Jianyan -- Wang, Shirong -- Wang, Cheng -- Spiering, Sean -- Kan, Natalia G -- Forcales, Sonia -- Puri, Pier Lorenzo -- Leone, Teresa C -- Marine, Joseph E -- Calkins, Hugh -- Kelly, Daniel P -- Judge, Daniel P -- Chen, Huei-Sheng Vincent -- R01 AR052779/AR/NIAMS NIH HHS/ -- R01 AR056712/AR/NIAMS NIH HHS/ -- R01 HL058493/HL/NHLBI NIH HHS/ -- R01 HL101189/HL/NHLBI NIH HHS/ -- R01 HL105194/HL/NHLBI NIH HHS/ -- TCR05004/Telethon/Italy -- England -- Nature. 2013 Feb 7;494(7435):105-10. doi: 10.1038/nature11799. Epub 2013 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Del E. Webb Neuroscience, Aging & Stem Cell Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23354045" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Age of Onset ; Apoptosis/genetics ; Arrhythmogenic Right Ventricular ; Dysplasia/genetics/*metabolism/*pathology/physiopathology ; Cellular Reprogramming ; Culture Media/pharmacology ; Embryoid Bodies/drug effects/physiology ; Energy Metabolism/genetics ; Fatty Acids/metabolism ; Fibroblasts/metabolism/pathology ; Glucose/metabolism ; Glycolysis ; Humans ; Induced Pluripotent Stem Cells/metabolism/*pathology ; Lipogenesis/genetics ; *Models, Biological ; Myocardial Contraction/drug effects ; Myocytes, Cardiac/pathology ; PPAR alpha/metabolism ; PPAR gamma/metabolism ; Phenotype ; Plakophilins/genetics ; Time Factors ; beta Catenin/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2014-08-01
    Description: Chemoresistance is a serious limitation of cancer treatment. Until recently, almost all the work done to study this limitation has been restricted to tumour cells. Here we identify a novel molecular mechanism by which endothelial cells regulate chemosensitivity. We establish that specific targeting of focal adhesion kinase (FAK; also known as PTK2) in endothelial cells is sufficient to induce tumour-cell sensitization to DNA-damaging therapies and thus inhibit tumour growth in mice. The clinical relevance of this work is supported by our observations that low blood vessel FAK expression is associated with complete remission in human lymphoma. Our study shows that deletion of FAK in endothelial cells has no apparent effect on blood vessel function per se, but induces increased apoptosis and decreased proliferation within perivascular tumour-cell compartments of doxorubicin- and radiotherapy-treated mice. Mechanistically, we demonstrate that endothelial-cell FAK is required for DNA-damage-induced NF-kappaB activation in vivo and in vitro, and the production of cytokines from endothelial cells. Moreover, loss of endothelial-cell FAK reduces DNA-damage-induced cytokine production, thus enhancing chemosensitization of tumour cells to DNA-damaging therapies in vitro and in vivo. Overall, our data identify endothelial-cell FAK as a regulator of tumour chemosensitivity. Furthermore, we anticipate that this proof-of-principle data will be a starting point for the development of new possible strategies to regulate chemosensitization by targeting endothelial-cell FAK specifically.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533916/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533916/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tavora, Bernardo -- Reynolds, Louise E -- Batista, Silvia -- Demircioglu, Fevzi -- Fernandez, Isabelle -- Lechertier, Tanguy -- Lees, Delphine M -- Wong, Ping-Pui -- Alexopoulou, Annika -- Elia, George -- Clear, Andrew -- Ledoux, Adeline -- Hunter, Jill -- Perkins, Neil -- Gribben, John G -- Hodivala-Dilke, Kairbaan M -- 12007/Cancer Research UK/United Kingdom -- C9218/A12007/Cancer Research UK/United Kingdom -- G0901609/Medical Research Council/United Kingdom -- P01 CA081534/CA/NCI NIH HHS/ -- P01 CA95426/CA/NCI NIH HHS/ -- England -- Nature. 2014 Oct 2;514(7520):112-6. doi: 10.1038/nature13541. Epub 2014 Jul 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Adhesion and Angiogenesis Laboratory, Centre for Tumour Biology, Barts Cancer Institute, CR-UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. ; 1] Adhesion and Angiogenesis Laboratory, Centre for Tumour Biology, Barts Cancer Institute, CR-UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK [2]. ; Barts Cancer Institute, CR-UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. ; Centre for Haemato-Oncology, Barts Cancer Institute, CR-UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. ; Institute for Cell and Molecular Biosciences (ICaMB), Medical School, Newcastle University, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079333" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus/drug effects ; Animals ; Apoptosis/drug effects/radiation effects ; Cell Nucleus/drug effects/metabolism ; Cell Proliferation/drug effects/radiation effects ; Cytokines/biosynthesis ; *DNA Damage/drug effects/genetics ; Doxorubicin/pharmacology/therapeutic use ; Drug Resistance, Neoplasm/*drug effects/genetics ; Endothelial Cells/*drug effects/*enzymology/metabolism ; Focal Adhesion Protein-Tyrosine Kinases/deficiency/genetics/*metabolism ; Humans ; Mice ; NF-kappa B/metabolism ; Neoplasms/drug therapy/genetics/pathology/radiotherapy ; Phosphorylation/drug effects
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  • 7
    Publication Date: 2014-05-16
    Description: Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is essential for normal brain growth and cognitive function. Consistent with its importance in the brain, DHA is highly enriched in brain phospholipids. Despite being an abundant fatty acid in brain phospholipids, DHA cannot be de novo synthesized in brain and must be imported across the blood-brain barrier, but mechanisms for DHA uptake in brain have remained enigmatic. Here we identify a member of the major facilitator superfamily--Mfsd2a (previously an orphan transporter)--as the major transporter for DHA uptake into brain. Mfsd2a is found to be expressed exclusively in endothelium of the blood-brain barrier of micro-vessels. Lipidomic analysis indicates that Mfsd2a-deficient (Mfsd2a-knockout) mice show markedly reduced levels of DHA in brain accompanied by neuronal cell loss in hippocampus and cerebellum, as well as cognitive deficits and severe anxiety, and microcephaly. Unexpectedly, cell-based studies indicate that Mfsd2a transports DHA in the form of lysophosphatidylcholine (LPC), but not unesterified fatty acid, in a sodium-dependent manner. Notably, Mfsd2a transports common plasma LPCs carrying long-chain fatty acids such LPC oleate and LPC palmitate, but not LPCs with less than a 14-carbon acyl chain. Moreover, we determine that the phosphor-zwitterionic headgroup of LPC is critical for transport. Importantly, Mfsd2a-knockout mice have markedly reduced uptake of labelled LPC DHA, and other LPCs, from plasma into brain, demonstrating that Mfsd2a is required for brain uptake of DHA. Our findings reveal an unexpected essential physiological role of plasma-derived LPCs in brain growth and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nguyen, Long N -- Ma, Dongliang -- Shui, Guanghou -- Wong, Peiyan -- Cazenave-Gassiot, Amaury -- Zhang, Xiaodong -- Wenk, Markus R -- Goh, Eyleen L K -- Silver, David L -- England -- Nature. 2014 May 22;509(7501):503-6. doi: 10.1038/nature13241. Epub 2014 May 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, 169857 Singapore. ; Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, 169857 Singapore. ; Department of Biochemistry, National University of Singapore, 8 Medical Drive, Block MD7, 117597 Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24828044" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety/physiopathology ; Biological Transport ; Blood-Brain Barrier/metabolism ; Brain/*metabolism/pathology/physiopathology ; Cognition Disorders/pathology/physiopathology ; Docosahexaenoic Acids/deficiency/*metabolism ; Endothelium, Vascular/metabolism ; Female ; Lysophosphatidylcholines/chemistry/metabolism ; Male ; Membrane Transport Proteins/deficiency/genetics/*metabolism ; Mice ; Mice, Knockout ; Microcephaly/metabolism/pathology ; Microvessels/metabolism ; Neurons/metabolism/pathology ; Organ Size ; Sodium/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2014-07-11
    Description: Cancer cells have been at the centre of cell metabolism research, but the metabolism of stromal and immune cells has received less attention. Nonetheless, these cells influence the progression of malignant, inflammatory and metabolic disorders. Here we discuss the metabolic adaptations of stromal and immune cells in health and disease, and highlight how metabolism determines their differentiation and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghesquiere, Bart -- Wong, Brian W -- Kuchnio, Anna -- Carmeliet, Peter -- England -- Nature. 2014 Jul 10;511(7508):167-76. doi: 10.1038/nature13312.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, Department of Oncology, University of Leuven, Leuven B-3000, Belgium [2] Laboratory of Angiogenesis and Neurovascular Link, Vesalius Research Center, VIB, Leuven B-3000, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008522" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Endothelial Cells/cytology/enzymology/metabolism ; Glycolysis ; Humans ; Macrophages/cytology/*metabolism ; Neoplasms/metabolism/pathology ; Stromal Cells/cytology/enzymology/*metabolism ; T-Lymphocytes/cytology/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2015-02-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miao, Xin -- Tang, Yanhong -- Wong, Christina W Y -- England -- Nature. 2015 Feb 26;518(7540):483. doi: 10.1038/518483d.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harbin Institute of Technology, Harbin, China. ; Northeast Agricultural University, Harbin, China. ; The Hong Kong Polytechnic University, Kowloon, Hong Kong.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25719657" target="_blank"〉PubMed〈/a〉
    Keywords: China ; *Ecosystem ; Environmental Policy/economics/*legislation & jurisprudence ; Environmental Pollution/*analysis/economics/*legislation & ; jurisprudence/prevention & control ; Human Migration ; Industrial Waste/analysis/economics/legislation & jurisprudence ; Industry/*legislation & jurisprudence/trends ; *Poverty
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-10-08
    Description: Activation of oncogenes by mechanisms other than genetic aberrations such as mutations, translocations, or amplifications is largely undefined. Here we report a novel isoform of the anaplastic lymphoma kinase (ALK) that is expressed in approximately 11% of melanomas and sporadically in other human cancer types, but not in normal tissues. The novel ALK transcript initiates from a de novo alternative transcription initiation (ATI) site in ALK intron 19, and was termed ALK(ATI). In ALK(ATI)-expressing tumours, the ATI site is enriched for H3K4me3 and RNA polymerase II, chromatin marks characteristic of active transcription initiation sites. ALK(ATI) is expressed from both ALK alleles, and no recurrent genetic aberrations are found at the ALK locus, indicating that the transcriptional activation is independent of genetic aberrations at the ALK locus. The ALK(ATI) transcript encodes three proteins with molecular weights of 61.1, 60.8 and 58.7 kilodaltons, consisting primarily of the intracellular tyrosine kinase domain. ALK(ATI) stimulates multiple oncogenic signalling pathways, drives growth-factor-independent cell proliferation in vitro, and promotes tumorigenesis in vivo in mouse models. ALK inhibitors can suppress the kinase activity of ALK(ATI), suggesting that patients with ALK(ATI)-expressing tumours may benefit from ALK inhibitors. Our findings suggest a novel mechanism of oncogene activation in cancer through de novo alternative transcription initiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wiesner, Thomas -- Lee, William -- Obenauf, Anna C -- Ran, Leili -- Murali, Rajmohan -- Zhang, Qi Fan -- Wong, Elissa W P -- Hu, Wenhuo -- Scott, Sasinya N -- Shah, Ronak H -- Landa, Inigo -- Button, Julia -- Lailler, Nathalie -- Sboner, Andrea -- Gao, Dong -- Murphy, Devan A -- Cao, Zhen -- Shukla, Shipra -- Hollmann, Travis J -- Wang, Lu -- Borsu, Laetitia -- Merghoub, Taha -- Schwartz, Gary K -- Postow, Michael A -- Ariyan, Charlotte E -- Fagin, James A -- Zheng, Deyou -- Ladanyi, Marc -- Busam, Klaus J -- Berger, Michael F -- Chen, Yu -- Chi, Ping -- DP2 CA174499/CA/NCI NIH HHS/ -- DP2CA174499/CA/NCI NIH HHS/ -- K08 CA151660/CA/NCI NIH HHS/ -- K08CA140946/CA/NCI NIH HHS/ -- K08CA151660/CA/NCI NIH HHS/ -- P01 CA129243/CA/NCI NIH HHS/ -- P01CA12943/CA/NCI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- P50 CA172012/CA/NCI NIH HHS/ -- P50CA172012/CA/NCI NIH HHS/ -- England -- Nature. 2015 Oct 15;526(7573):453-7. doi: 10.1038/nature15258. Epub 2015 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York 10065, USA. ; Department of Dermatology, Medical University of Graz, 8010 Graz, Austria. ; Computational Biology Program, Memorial Sloan Kettering Cancer Center, New York 10065, USA. ; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York 10065, USA. ; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York 10065, USA. ; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York 10065, USA. ; Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York 10065, USA. ; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York 10065, USA. ; Institute for Computational Biomedicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York 10065, USA. ; Institute for Precision Medicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York, USA. ; Immunology Program, Memorial Sloan Kettering Cancer Center 10065, New York, USA. ; Herbert Irving Comprehensive Cancer Center, Columbia University Cancer Center, New York 10032, USA. ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York 10065, USA. ; Department of Medicine, Weill Cornell Medical College, New York 10065, USA. ; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York 10065, USA. ; Department of Neurology, Albert Einstein College of Medicine, New York 10461, USA. ; Department of Genetics, Albert Einstein College of Medicine, New York 10461, USA. ; Department of Neuroscience, Albert Einstein College of Medicine, New York 10461, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26444240" target="_blank"〉PubMed〈/a〉
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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