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  • 1
    Publication Date: 2010-11-06
    Description: Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified 〉300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235490/" 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/PMC3235490/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International HIV Controllers Study -- Pereyra, Florencia -- Jia, Xiaoming -- McLaren, Paul J -- Telenti, Amalio -- de Bakker, Paul I W -- Walker, Bruce D -- Ripke, Stephan -- Brumme, Chanson J -- Pulit, Sara L -- Carrington, Mary -- Kadie, Carl M -- Carlson, Jonathan M -- Heckerman, David -- Graham, Robert R -- Plenge, Robert M -- Deeks, Steven G -- Gianniny, Lauren -- Crawford, Gabriel -- Sullivan, Jordan -- Gonzalez, Elena -- Davies, Leela -- Camargo, Amy -- Moore, Jamie M -- Beattie, Nicole -- Gupta, Supriya -- Crenshaw, Andrew -- Burtt, Noel P -- Guiducci, Candace -- Gupta, Namrata -- Gao, Xiaojiang -- Qi, Ying -- Yuki, Yuko -- Piechocka-Trocha, Alicja -- Cutrell, Emily -- Rosenberg, Rachel -- Moss, Kristin L -- Lemay, Paul -- O'Leary, Jessica -- Schaefer, Todd -- Verma, Pranshu -- Toth, Ildiko -- Block, Brian -- Baker, Brett -- Rothchild, Alissa -- Lian, Jeffrey -- Proudfoot, Jacqueline -- Alvino, Donna Marie L -- Vine, Seanna -- Addo, Marylyn M -- Allen, Todd M -- Altfeld, Marcus -- Henn, Matthew R -- Le Gall, Sylvie -- Streeck, Hendrik -- Haas, David W -- Kuritzkes, Daniel R -- Robbins, Gregory K -- Shafer, Robert W -- Gulick, Roy M -- Shikuma, Cecilia M -- Haubrich, Richard -- Riddler, Sharon -- Sax, Paul E -- Daar, Eric S -- Ribaudo, Heather J -- Agan, Brian -- Agarwal, Shanu -- Ahern, Richard L -- Allen, Brady L -- Altidor, Sherly -- Altschuler, Eric L -- Ambardar, Sujata -- Anastos, Kathryn -- Anderson, Ben -- Anderson, Val -- Andrady, Ushan -- Antoniskis, Diana -- Bangsberg, David -- Barbaro, Daniel -- Barrie, William -- Bartczak, J -- Barton, Simon -- Basden, Patricia -- Basgoz, Nesli -- Bazner, Suzane -- Bellos, Nicholaos C -- Benson, Anne M -- Berger, Judith -- Bernard, Nicole F -- Bernard, Annette M -- Birch, Christopher -- Bodner, Stanley J -- Bolan, Robert K -- Boudreaux, Emilie T -- Bradley, Meg -- Braun, James F -- Brndjar, Jon E -- Brown, Stephen J -- Brown, Katherine -- Brown, Sheldon T -- Burack, Jedidiah -- Bush, Larry M -- Cafaro, Virginia -- Campbell, Omobolaji -- Campbell, John -- Carlson, Robert H -- Carmichael, J Kevin -- Casey, Kathleen K -- Cavacuiti, Chris -- Celestin, Gregory -- Chambers, Steven T -- Chez, Nancy -- Chirch, Lisa M -- Cimoch, Paul J -- Cohen, Daniel -- Cohn, Lillian E -- Conway, Brian -- Cooper, David A -- Cornelson, Brian -- Cox, David T -- Cristofano, Michael V -- Cuchural, George Jr -- Czartoski, Julie L -- Dahman, Joseph M -- Daly, Jennifer S -- Davis, Benjamin T -- Davis, Kristine -- Davod, Sheila M -- DeJesus, Edwin -- Dietz, Craig A -- Dunham, Eleanor -- Dunn, Michael E -- Ellerin, Todd B -- Eron, Joseph J -- Fangman, John J W -- Farel, Claire E -- Ferlazzo, Helen -- Fidler, Sarah -- Fleenor-Ford, Anita -- Frankel, Renee -- Freedberg, Kenneth A -- French, Neel K -- Fuchs, Jonathan D -- Fuller, Jon D -- Gaberman, Jonna -- Gallant, Joel E -- Gandhi, Rajesh T -- Garcia, Efrain -- Garmon, Donald -- Gathe, Joseph C Jr -- Gaultier, Cyril R -- Gebre, Wondwoosen -- Gilman, Frank D -- Gilson, Ian -- Goepfert, Paul A -- Gottlieb, Michael S -- Goulston, Claudia -- Groger, Richard K -- Gurley, T Douglas -- Haber, Stuart -- Hardwicke, Robin -- Hardy, W David -- Harrigan, P Richard -- Hawkins, Trevor N -- Heath, Sonya -- Hecht, Frederick M -- Henry, W Keith -- Hladek, Melissa -- Hoffman, Robert P -- Horton, James M -- Hsu, Ricky K -- Huhn, Gregory D -- Hunt, Peter -- Hupert, Mark J -- Illeman, Mark L -- Jaeger, Hans -- Jellinger, Robert M -- John, Mina -- Johnson, Jennifer A -- Johnson, Kristin L -- Johnson, Heather -- Johnson, Kay -- Joly, Jennifer -- Jordan, Wilbert C -- Kauffman, Carol A -- Khanlou, Homayoon -- Killian, Robert K -- Kim, Arthur Y -- Kim, David D -- Kinder, Clifford A -- Kirchner, Jeffrey T -- Kogelman, Laura -- Kojic, Erna Milunka -- Korthuis, P Todd -- Kurisu, Wayne -- Kwon, Douglas S -- LaMar, Melissa -- Lampiris, Harry -- Lanzafame, Massimiliano -- Lederman, Michael M -- Lee, David M -- Lee, Jean M L -- Lee, Marah J -- Lee, Edward T Y -- Lemoine, Janice -- Levy, Jay A -- Llibre, Josep M -- Liguori, Michael A -- Little, Susan J -- Liu, Anne Y -- Lopez, Alvaro J -- Loutfy, Mono R -- Loy, Dawn -- Mohammed, Debbie Y -- Man, Alan -- Mansour, Michael K -- Marconi, Vincent C -- Markowitz, Martin -- Marques, Rui -- Martin, Jeffrey N -- Martin, Harold L Jr -- Mayer, Kenneth Hugh -- McElrath, M Juliana -- McGhee, Theresa A -- McGovern, Barbara H -- McGowan, Katherine -- McIntyre, Dawn -- Mcleod, Gavin X -- Menezes, Prema -- Mesa, Greg -- Metroka, Craig E -- Meyer-Olson, Dirk -- Miller, Andy O -- Montgomery, Kate -- Mounzer, Karam C -- Nagami, Ellen H -- Nagin, Iris -- Nahass, Ronald G -- Nelson, Margret O -- Nielsen, Craig -- Norene, David L -- O'Connor, David H -- Ojikutu, Bisola O -- Okulicz, Jason -- Oladehin, Olakunle O -- Oldfield, Edward C 3rd -- Olender, Susan A -- Ostrowski, Mario -- Owen, William F Jr -- Pae, Eunice -- Parsonnet, Jeffrey -- Pavlatos, Andrew M -- Perlmutter, Aaron M -- Pierce, Michael N -- Pincus, Jonathan M -- Pisani, Leandro -- Price, Lawrence Jay -- Proia, Laurie -- Prokesch, Richard C -- Pujet, Heather Calderon -- Ramgopal, Moti -- Rathod, Almas -- Rausch, Michael -- Ravishankar, J -- Rhame, Frank S -- Richards, Constance Shamuyarira -- Richman, Douglas D -- Rodes, Berta -- Rodriguez, Milagros -- Rose, Richard C 3rd -- Rosenberg, Eric S -- Rosenthal, Daniel -- Ross, Polly E -- Rubin, David S -- Rumbaugh, Elease -- Saenz, Luis -- Salvaggio, Michelle R -- Sanchez, William C -- Sanjana, Veeraf M -- Santiago, Steven -- Schmidt, Wolfgang -- Schuitemaker, Hanneke -- Sestak, Philip M -- Shalit, Peter -- Shay, William -- Shirvani, Vivian N -- Silebi, Vanessa I -- Sizemore, James M Jr -- Skolnik, Paul R -- Sokol-Anderson, Marcia -- Sosman, James M -- Stabile, Paul -- Stapleton, Jack T -- Starrett, Sheree -- Stein, Francine -- Stellbrink, Hans-Jurgen -- Sterman, F Lisa -- Stone, Valerie E -- Stone, David R -- Tambussi, Giuseppe -- Taplitz, Randy A -- Tedaldi, Ellen M -- Theisen, William -- Torres, Richard -- Tosiello, Lorraine -- Tremblay, Cecile -- Tribble, Marc A -- Trinh, Phuong D -- Tsao, Alice -- Ueda, Peggy -- Vaccaro, Anthony -- Valadas, Emilia -- Vanig, Thanes J -- Vecino, Isabel -- Vega, Vilma M -- Veikley, Wenoah -- Wade, Barbara H -- Walworth, Charles -- Wanidworanun, Chingchai -- Ward, Douglas J -- Warner, Daniel A -- Weber, Robert D -- Webster, Duncan -- Weis, Steve -- Wheeler, David A -- White, David J -- Wilkins, Ed -- Winston, Alan -- Wlodaver, Clifford G -- van't Wout, Angelique -- Wright, David P -- Yang, Otto O -- Yurdin, David L -- Zabukovic, Brandon W -- Zachary, Kimon C -- Zeeman, Beth -- Zhao, Meng -- AI030914/AI/NIAID NIH HHS/ -- AI068636/AI/NIAID NIH HHS/ -- AI069415/AI/NIAID NIH HHS/ -- AI069419/AI/NIAID NIH HHS/ -- AI069423/AI/NIAID NIH HHS/ -- AI069424/AI/NIAID NIH HHS/ -- AI069428/AI/NIAID NIH HHS/ -- AI069432/AI/NIAID NIH HHS/ -- AI069434/AI/NIAID NIH HHS/ -- AI069450/AI/NIAID NIH HHS/ -- AI069452/AI/NIAID NIH HHS/ -- AI069465/AI/NIAID NIH HHS/ -- AI069471/AI/NIAID NIH HHS/ -- AI069472/AI/NIAID NIH HHS/ -- AI069474/AI/NIAID NIH HHS/ -- AI069477/AI/NIAID NIH HHS/ -- AI069484/AI/NIAID NIH HHS/ -- AI069495/AI/NIAID NIH HHS/ -- AI069501/AI/NIAID NIH HHS/ -- AI069502/AI/NIAID NIH HHS/ -- AI069511/AI/NIAID NIH HHS/ -- AI069513/AI/NIAID NIH HHS/ -- AI069532/AI/NIAID NIH HHS/ -- AI069556/AI/NIAID NIH HHS/ -- AI077505/AI/NIAID NIH HHS/ -- AI087145/AI/NIAID NIH HHS/ -- AI25859/AI/NIAID NIH HHS/ -- AI27661/AI/NIAID NIH HHS/ -- AI28568/AI/NIAID NIH HHS/ -- AI30914/AI/NIAID NIH HHS/ -- AI34835/AI/NIAID NIH HHS/ -- AI34853/AI/NIAID NIH HHS/ -- AI38844/AI/NIAID NIH HHS/ -- AI46370/AI/NIAID NIH HHS/ -- AI68634/AI/NIAID NIH HHS/ -- AI69467/AI/NIAID NIH HHS/ -- AL32782/PHS HHS/ -- HHSN261200800001E/PHS HHS/ -- K23 DA019809/DA/NIDA NIH HHS/ -- K24 AI051966/AI/NIAID NIH HHS/ -- K24 AI064086/AI/NIAID NIH HHS/ -- K24 AI064086-05/AI/NIAID NIH HHS/ -- K24 AI069994/AI/NIAID NIH HHS/ -- K24 AI069994-04/AI/NIAID NIH HHS/ -- K24 AI069994-05/AI/NIAID NIH HHS/ -- K24AI069994/AI/NIAID NIH HHS/ -- KL2 RR024977/RR/NCRR NIH HHS/ -- MH071205/MH/NIMH NIH HHS/ -- MH085520/MH/NIMH NIH HHS/ -- P-30 AI27763/AI/NIAID NIH HHS/ -- P-30-AI060354/AI/NIAID NIH HHS/ -- P30 AI027763/AI/NIAID NIH HHS/ -- P30 AI027763-19/AI/NIAID NIH HHS/ -- P30 AI027763-20/AI/NIAID NIH HHS/ -- P30 AI050410/AI/NIAID NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- P30 AI060354-08/AI/NIAID NIH HHS/ -- P30 AI060354-09/AI/NIAID NIH HHS/ -- R01 AI028568/AI/NIAID NIH HHS/ -- R01 AI028568-18/AI/NIAID NIH HHS/ -- R01 AI028568-19/AI/NIAID NIH HHS/ -- R01 AI028568-20/AI/NIAID NIH HHS/ -- R01 AI030914/AI/NIAID NIH HHS/ -- R01 AI030914-16/AI/NIAID NIH HHS/ -- R01 AI030914-17/AI/NIAID NIH HHS/ -- R01 AI077505/AI/NIAID NIH HHS/ -- R01 AI077505-04/AI/NIAID NIH HHS/ -- R01 AI077505-05/AI/NIAID NIH HHS/ -- R01 AI087145/AI/NIAID NIH HHS/ -- R01 AI087145-01/AI/NIAID NIH HHS/ -- R01 AI087145-02/AI/NIAID NIH HHS/ -- R01 MH054907/MH/NIMH NIH HHS/ -- R01 MH071205/MH/NIMH NIH HHS/ -- R01 MH071205-04/MH/NIMH NIH HHS/ -- R01 MH071205-05/MH/NIMH NIH HHS/ -- R24 AI067039/AI/NIAID NIH HHS/ -- R24 AI067039-06/AI/NIAID NIH HHS/ -- R24 AI067039-07/AI/NIAID NIH HHS/ -- R37 AI028568/AI/NIAID NIH HHS/ -- R37 AI028568-15/AI/NIAID NIH HHS/ -- RR024975/RR/NCRR NIH HHS/ -- T32 AI007061/AI/NIAID NIH HHS/ -- TL1 RR024978/RR/NCRR NIH HHS/ -- U01 AI027661-18/AI/NIAID NIH HHS/ -- U01 AI027661-19/AI/NIAID NIH HHS/ -- U01 AI032782-13/AI/NIAID NIH HHS/ -- U01 AI034835-07/AI/NIAID NIH HHS/ -- U01 AI034835-07S3/AI/NIAID NIH HHS/ -- U01 AI034853/AI/NIAID NIH HHS/ -- U01 AI034853-11/AI/NIAID NIH HHS/ -- U01 AI034853-12/AI/NIAID NIH HHS/ -- U01 AI038844-04/AI/NIAID NIH HHS/ -- U01 AI038844-04S1/AI/NIAID NIH HHS/ -- U01 AI038844-04S2/AI/NIAID NIH HHS/ -- U01 AI038844-04S3/AI/NIAID NIH HHS/ -- U01 AI046370-04/AI/NIAID NIH HHS/ -- U01 AI046370-05/AI/NIAID NIH HHS/ -- U01 AI069419/AI/NIAID NIH HHS/ -- U01 AI069419-05/AI/NIAID NIH HHS/ -- U01 AI069419-06/AI/NIAID NIH HHS/ -- U01 AI069423/AI/NIAID NIH HHS/ -- U01 AI069423-05/AI/NIAID NIH HHS/ -- U01 AI069423-06/AI/NIAID NIH HHS/ -- U01 AI069424/AI/NIAID NIH HHS/ -- U01 AI069424-05/AI/NIAID NIH HHS/ -- U01 AI069424-06/AI/NIAID NIH HHS/ -- U01 AI069428/AI/NIAID NIH HHS/ -- U01 AI069428-05/AI/NIAID NIH HHS/ -- U01 AI069428-06/AI/NIAID NIH HHS/ -- U01 AI069432/AI/NIAID NIH HHS/ -- U01 AI069432-05/AI/NIAID NIH HHS/ -- U01 AI069432-06/AI/NIAID NIH HHS/ -- U01 AI069434/AI/NIAID NIH HHS/ -- U01 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HHS/ -- U01 AI069484-06/AI/NIAID NIH HHS/ -- U01 AI069495/AI/NIAID NIH HHS/ -- U01 AI069495-05/AI/NIAID NIH HHS/ -- U01 AI069495-06/AI/NIAID NIH HHS/ -- U01 AI069501/AI/NIAID NIH HHS/ -- U01 AI069501-05/AI/NIAID NIH HHS/ -- U01 AI069501-06/AI/NIAID NIH HHS/ -- U01 AI069502/AI/NIAID NIH HHS/ -- U01 AI069502-05/AI/NIAID NIH HHS/ -- U01 AI069502-06/AI/NIAID NIH HHS/ -- U01 AI069511/AI/NIAID NIH HHS/ -- U01 AI069511-05/AI/NIAID NIH HHS/ -- U01 AI069511-06/AI/NIAID NIH HHS/ -- U01 AI069513-05/AI/NIAID NIH HHS/ -- U01 AI069513-06/AI/NIAID NIH HHS/ -- U01 AI069532/AI/NIAID NIH HHS/ -- U01 AI069532-05/AI/NIAID NIH HHS/ -- U01 AI069532-06/AI/NIAID NIH HHS/ -- U01 AI069556-05/AI/NIAID NIH HHS/ -- U01 AI069556-06/AI/NIAID NIH HHS/ -- U01 MH085520/MH/NIMH NIH HHS/ -- U01 MH085520-01/MH/NIMH NIH HHS/ -- UL1 RR024131/RR/NCRR NIH HHS/ -- UL1 RR024131-06/RR/NCRR NIH HHS/ -- UL1 RR024131-07/RR/NCRR NIH HHS/ -- UL1 RR024975/RR/NCRR NIH HHS/ -- UL1 RR024975-04/RR/NCRR NIH HHS/ -- UL1 RR024975-05/RR/NCRR NIH HHS/ -- UM1 AI068634/AI/NIAID NIH HHS/ -- UM1 AI068634-06/AI/NIAID NIH HHS/ -- UM1 AI068634-07/AI/NIAID NIH HHS/ -- UM1 AI068636-06/AI/NIAID NIH HHS/ -- UM1 AI068636-07/AI/NIAID NIH HHS/ -- UM1 AI069477/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2010 Dec 10;330(6010):1551-7. doi: 10.1126/science.1195271. Epub 2010 Nov 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology (MIT) and Harvard, Boston, MA, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051598" target="_blank"〉PubMed〈/a〉
    Keywords: African Americans/genetics ; Alleles ; Amino Acids/physiology ; *Antigen Presentation ; CD8-Positive T-Lymphocytes/immunology ; Cohort Studies ; Disease Progression ; European Continental Ancestry Group/genetics ; *Genes, MHC Class I ; Genome-Wide Association Study ; HIV Antigens/immunology ; HIV Infections/ethnology/*genetics/*immunology/virology ; HIV Long-Term Survivors ; *HIV-1/immunology ; HLA-A Antigens/chemistry/genetics/immunology/metabolism ; HLA-B Antigens/chemistry/*genetics/immunology/metabolism ; HLA-C Antigens/chemistry/genetics/immunology/metabolism ; Haplotypes ; Hispanic Americans/genetics ; Humans ; Immunity, Innate ; Logistic Models ; Models, Molecular ; Polymorphism, Single Nucleotide ; Protein Conformation ; Viral Load
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-03-29
    Description: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" 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/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence/genetics ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Genes, Essential/genetics ; Genome/genetics ; Humans ; Mice ; *Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/analysis/genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/genetics ; Transcriptome/*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: 2014-06-07
    Description: Sheep (Ovis aries) are a major source of meat, milk, and fiber in the form of wool and represent a distinct class of animals that have a specialized digestive organ, the rumen, that carries out the initial digestion of plant material. We have developed and analyzed a high-quality reference sheep genome and transcriptomes from 40 different tissues. We identified highly expressed genes encoding keratin cross-linking proteins associated with rumen evolution. We also identified genes involved in lipid metabolism that had been amplified and/or had altered tissue expression patterns. This may be in response to changes in the barrier lipids of the skin, an interaction between lipid metabolism and wool synthesis, and an increased role of volatile fatty acids in ruminants compared with nonruminant animals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157056/" 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/PMC4157056/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Yu -- Xie, Min -- Chen, Wenbin -- Talbot, Richard -- Maddox, Jillian F -- Faraut, Thomas -- Wu, Chunhua -- Muzny, Donna M -- Li, Yuxiang -- Zhang, Wenguang -- Stanton, Jo-Ann -- Brauning, Rudiger -- Barris, Wesley C -- Hourlier, Thibaut -- Aken, Bronwen L -- Searle, Stephen M J -- Adelson, David L -- Bian, Chao -- Cam, Graham R -- Chen, Yulin -- Cheng, Shifeng -- DeSilva, Udaya -- Dixen, Karen -- Dong, Yang -- Fan, Guangyi -- Franklin, Ian R -- Fu, Shaoyin -- Fuentes-Utrilla, Pablo -- Guan, Rui -- Highland, Margaret A -- Holder, Michael E -- Huang, Guodong -- Ingham, Aaron B -- Jhangiani, Shalini N -- Kalra, Divya -- Kovar, Christie L -- Lee, Sandra L -- Liu, Weiqing -- Liu, Xin -- Lu, Changxin -- Lv, Tian -- Mathew, Tittu -- McWilliam, Sean -- Menzies, Moira -- Pan, Shengkai -- Robelin, David -- Servin, Bertrand -- Townley, David -- Wang, Wenliang -- Wei, Bin -- White, Stephen N -- Yang, Xinhua -- Ye, Chen -- Yue, Yaojing -- Zeng, Peng -- Zhou, Qing -- Hansen, Jacob B -- Kristiansen, Karsten -- Gibbs, Richard A -- Flicek, Paul -- Warkup, Christopher C -- Jones, Huw E -- Oddy, V Hutton -- Nicholas, Frank W -- McEwan, John C -- Kijas, James W -- Wang, Jun -- Worley, Kim C -- Archibald, Alan L -- Cockett, Noelle -- Xu, Xun -- Wang, Wen -- Dalrymple, Brian P -- 095908/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- BB/1025360/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I025328/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I025360/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I025506/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- U54 HG003273/HG/NHGRI NIH HHS/ -- WT095908/Wellcome Trust/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2014 Jun 6;344(6188):1168-73. doi: 10.1126/science.1252806.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Commonwealth Scientific and Industrial Research Organisation Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. ; BGI-Shenzhen, Shenzhen 518083, China. ; Ediburgh Genomics, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. ; Utah State University, Logan, UT 84322-4815, USA. ; Institut National de la Recherche Agronomique, Laboratoire de Genetique Cellulaire, UMR 444, Castanet-Tolosan F-31326, France. ; Utah State University, Logan, UT 84322-1435, USA. ; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. ; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. Inner Mongolia Agricultural University, Hohhot 010018, China. Institute of ATCG, Nei Mongol Bio-Information, Hohhot, China. ; Department of Anatomy, University of Otago, Dunedin 9054, New Zealand. ; AgResearch, Invermay Agricultural Centre, Mosgiel 9053, New Zealand. ; Commonwealth Scientific and Industrial Research Organisation Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ; College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. ; Department of Biology, University of Copenhagen, DK-2100 Copenhagen O, Denmark. ; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. ; Inner Mongolia Agricultural University, Hohhot 010018, China. ; U.S. Department of Agriculture Agricultural Research Service Animal Disease Research Unit, Pullman, WA 99164, USA. Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA. ; BGI-Shenzhen, Shenzhen 518083, China. Maize Research Institute, Sichuan Agricultural University, Chengdu 611130, China. ; Lanzhou Institute of Husbandry and Pharmaceutical Science, Lanzhou, 730050, China. ; Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark. ; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK. ; Biosciences Knowledge Transfer Network, The Roslin Institute, Easter Bush, Midlothian, EH25 9RG, UK. ; School of Environmental and Rural Science, University of New England, Armidale, NSW 2351, Australia. ; Faculty of Veterinary Science, University of Sydney, NSW 2006, Australia. ; BGI-Shenzhen, Shenzhen 518083, China. Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark. Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Macau University of Science and Technology, Macau 999078, China. ; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; Utah State University, Logan, UT 84322-1435, USA. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; BGI-Shenzhen, Shenzhen 518083, China. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu. ; Commonwealth Scientific and Industrial Research Organisation Animal Food and Health Sciences, St Lucia, QLD 4067, Australia. brian.dalrymple@csiro.au wwang@mail.kiz.ac.cn xuxun@genomics.cn alan.archibald@roslin.ed.ac.uk kworley@bcm.edu noelle.cockett@usu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24904168" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Fatty Acids, Volatile/metabolism/physiology ; Gene Expression Regulation ; Genome ; Keratins, Hair-Specific/genetics ; Lipid Metabolism/genetics/*physiology ; Molecular Sequence Data ; Phylogeny ; Rumen/metabolism/*physiology ; Sheep, Domestic/classification/*genetics/*metabolism ; Transcriptome ; Wool/growth & development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-11-05
    Description: The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) 〈 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR 〈 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4402723/" 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/PMC4402723/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Rubeis, Silvia -- He, Xin -- Goldberg, Arthur P -- Poultney, Christopher S -- Samocha, Kaitlin -- Cicek, A Erucment -- Kou, Yan -- Liu, Li -- Fromer, Menachem -- Walker, Susan -- Singh, Tarinder -- Klei, Lambertus -- Kosmicki, Jack -- Shih-Chen, Fu -- Aleksic, Branko -- Biscaldi, Monica -- Bolton, Patrick F -- Brownfeld, Jessica M -- Cai, Jinlu -- Campbell, Nicholas G -- Carracedo, Angel -- Chahrour, Maria H -- Chiocchetti, Andreas G -- Coon, Hilary -- Crawford, Emily L -- Curran, Sarah R -- Dawson, Geraldine -- Duketis, Eftichia -- Fernandez, Bridget A -- Gallagher, Louise -- Geller, Evan -- Guter, Stephen J -- Hill, R Sean -- Ionita-Laza, Juliana -- Jimenz Gonzalez, Patricia -- Kilpinen, Helena -- Klauck, Sabine M -- Kolevzon, Alexander -- Lee, Irene -- Lei, Irene -- Lei, Jing -- Lehtimaki, Terho -- Lin, Chiao-Feng -- Ma'ayan, Avi -- Marshall, Christian R -- McInnes, Alison L -- Neale, Benjamin -- Owen, Michael J -- Ozaki, Noriio -- Parellada, Mara -- Parr, Jeremy R -- Purcell, Shaun -- Puura, Kaija -- Rajagopalan, Deepthi -- Rehnstrom, Karola -- Reichenberg, Abraham -- Sabo, Aniko -- Sachse, Michael -- Sanders, Stephan J -- Schafer, Chad -- Schulte-Ruther, Martin -- Skuse, David -- Stevens, Christine -- Szatmari, Peter -- Tammimies, Kristiina -- Valladares, Otto -- Voran, Annette -- Li-San, Wang -- Weiss, Lauren A -- Willsey, A Jeremy -- Yu, Timothy W -- Yuen, Ryan K C -- DDD Study -- Homozygosity Mapping Collaborative for Autism -- UK10K Consortium -- Cook, Edwin H -- Freitag, Christine M -- Gill, Michael -- Hultman, Christina M -- Lehner, Thomas -- Palotie, Aaarno -- Schellenberg, Gerard D -- Sklar, Pamela -- State, Matthew W -- Sutcliffe, James S -- Walsh, Christiopher A -- Scherer, Stephen W -- Zwick, Michael E -- Barett, Jeffrey C -- Cutler, David J -- Roeder, Kathryn -- Devlin, Bernie -- Daly, Mark J -- Buxbaum, Joseph D -- 5UL1 RR024975/RR/NCRR NIH HHS/ -- MH077139/MH/NIMH NIH HHS/ -- MH089482/MH/NIMH NIH HHS/ -- MH095034/MH/NIMH NIH HHS/ -- P30 HD15052/HD/NICHD NIH HHS/ -- P50 HD055751/HD/NICHD NIH HHS/ -- R01 MH061009/MH/NIMH NIH HHS/ -- R01 MH083565/MH/NIMH NIH HHS/ -- R01 MH089482/MH/NIMH NIH HHS/ -- R01 MH094400/MH/NIMH NIH HHS/ -- R01 MH095797/MH/NIMH NIH HHS/ -- R01 MH097849/MH/NIMH NIH HHS/ -- R01 MH100229/MH/NIMH NIH HHS/ -- R01 NS073601/NS/NINDS NIH HHS/ -- R01MH083565/MH/NIMH NIH HHS/ -- R01MH089208/MH/NIMH NIH HHS/ -- R37 MH057881/MH/NIMH NIH HHS/ -- RC2MH089952/MH/NIMH NIH HHS/ -- T32 HG002295/HG/NHGRI NIH HHS/ -- U01 MH100209/MH/NIMH NIH HHS/ -- U01 MH100229/MH/NIMH NIH HHS/ -- U01 MH100233/MH/NIMH NIH HHS/ -- U01 MH100239/MH/NIMH NIH HHS/ -- U01MH100209/MH/NIMH NIH HHS/ -- U01MH100229/MH/NIMH NIH HHS/ -- U01MH100233/MH/NIMH NIH HHS/ -- U01MH100239/MH/NIMH NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- UL1TR000445/TR/NCATS NIH HHS/ -- WT091310/Wellcome Trust/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Nov 13;515(7526):209-15. doi: 10.1038/nature13772. Epub 2014 Oct 29.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363760" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Child Development Disorders, Pervasive/*genetics/pathology ; Chromatin/*genetics/metabolism ; Chromatin Assembly and Disassembly ; Exome/genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Germ-Line Mutation/genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation/*genetics ; Mutation, Missense/genetics ; Nerve Net/metabolism ; Odds Ratio ; Synapses/*metabolism ; Transcription, Genetic/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-07-27
    Description: Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662966/" 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/PMC3662966/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, David T W -- Jager, Natalie -- Kool, Marcel -- Zichner, Thomas -- Hutter, Barbara -- Sultan, Marc -- Cho, Yoon-Jae -- Pugh, Trevor J -- Hovestadt, Volker -- Stutz, Adrian M -- Rausch, Tobias -- Warnatz, Hans-Jorg -- Ryzhova, Marina -- Bender, Sebastian -- Sturm, Dominik -- Pleier, Sabrina -- Cin, Huriye -- Pfaff, Elke -- Sieber, Laura -- Wittmann, Andrea -- Remke, Marc -- Witt, Hendrik -- Hutter, Sonja -- Tzaridis, Theophilos -- Weischenfeldt, Joachim -- Raeder, Benjamin -- Avci, Meryem -- Amstislavskiy, Vyacheslav -- Zapatka, Marc -- Weber, Ursula D -- Wang, Qi -- Lasitschka, Barbel -- Bartholomae, Cynthia C -- Schmidt, Manfred -- von Kalle, Christof -- Ast, Volker -- Lawerenz, Chris -- Eils, Jurgen -- Kabbe, Rolf -- Benes, Vladimir -- van Sluis, Peter -- Koster, Jan -- Volckmann, Richard -- Shih, David -- Betts, Matthew J -- Russell, Robert B -- Coco, Simona -- Tonini, Gian Paolo -- Schuller, Ulrich -- Hans, Volkmar -- Graf, Norbert -- Kim, Yoo-Jin -- Monoranu, Camelia -- Roggendorf, Wolfgang -- Unterberg, Andreas -- Herold-Mende, Christel -- Milde, Till -- Kulozik, Andreas E -- von Deimling, Andreas -- Witt, Olaf -- Maass, Eberhard -- Rossler, Jochen -- Ebinger, Martin -- Schuhmann, Martin U -- Fruhwald, Michael C -- Hasselblatt, Martin -- Jabado, Nada -- Rutkowski, Stefan -- von Bueren, Andre O -- Williamson, Dan -- Clifford, Steven C -- McCabe, Martin G -- Collins, V Peter -- Wolf, Stephan -- Wiemann, Stefan -- Lehrach, Hans -- Brors, Benedikt -- Scheurlen, Wolfram -- Felsberg, Jorg -- Reifenberger, Guido -- Northcott, Paul A -- Taylor, Michael D -- Meyerson, Matthew -- Pomeroy, Scott L -- Yaspo, Marie-Laure -- Korbel, Jan O -- Korshunov, Andrey -- Eils, Roland -- Pfister, Stefan M -- Lichter, Peter -- P30 HD018655/HD/NICHD NIH HHS/ -- R01 CA109467/CA/NCI NIH HHS/ -- England -- Nature. 2012 Aug 2;488(7409):100-5. doi: 10.1038/nature11284.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg 69120, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22832583" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics ; Amino Acid Sequence ; Cell Transformation, Neoplastic ; Cerebellar Neoplasms/classification/diagnosis/*genetics/pathology ; Child ; Chromatin/metabolism ; Chromosomes, Human/genetics ; DEAD-box RNA Helicases/genetics ; DNA Helicases/genetics ; DNA-Binding Proteins/genetics ; Genome, Human/*genetics ; Genomics ; Hedgehog Proteins/metabolism ; High-Throughput Nucleotide Sequencing ; Histone Demethylases/genetics ; Humans ; Medulloblastoma/classification/diagnosis/*genetics/pathology ; Methylation ; Mutation/genetics ; Mutation Rate ; Neoplasm Proteins/genetics ; Nuclear Proteins/genetics ; Oncogene Proteins, Fusion/genetics ; Phosphoprotein Phosphatases/genetics ; Polyploidy ; Receptors, Cell Surface/genetics ; Sequence Analysis, RNA ; Signal Transduction ; T-Box Domain Proteins/genetics ; Transcription Factors/genetics ; Wnt Proteins/metabolism ; beta Catenin/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2014-08-29
    Description: Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227084/" 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/PMC4227084/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ho, Joshua W K -- Jung, Youngsook L -- Liu, Tao -- Alver, Burak H -- Lee, Soohyun -- Ikegami, Kohta -- Sohn, Kyung-Ah -- Minoda, Aki -- Tolstorukov, Michael Y -- Appert, Alex -- Parker, Stephen C J -- Gu, Tingting -- Kundaje, Anshul -- Riddle, Nicole C -- Bishop, Eric -- Egelhofer, Thea A -- Hu, Sheng'en Shawn -- Alekseyenko, Artyom A -- Rechtsteiner, Andreas -- Asker, Dalal -- Belsky, Jason A -- Bowman, Sarah K -- Chen, Q Brent -- Chen, Ron A-J -- Day, Daniel S -- Dong, Yan -- Dose, Andrea C -- Duan, Xikun -- Epstein, Charles B -- Ercan, Sevinc -- Feingold, Elise A -- Ferrari, Francesco -- Garrigues, Jacob M -- Gehlenborg, Nils -- Good, Peter J -- Haseley, Psalm -- He, Daniel -- Herrmann, Moritz -- Hoffman, Michael M -- Jeffers, Tess E -- Kharchenko, Peter V -- Kolasinska-Zwierz, Paulina -- Kotwaliwale, Chitra V -- Kumar, Nischay -- Langley, Sasha A -- Larschan, Erica N -- Latorre, Isabel -- Libbrecht, Maxwell W -- Lin, Xueqiu -- Park, Richard -- Pazin, Michael J -- Pham, Hoang N -- Plachetka, Annette -- Qin, Bo -- Schwartz, Yuri B -- Shoresh, Noam -- Stempor, Przemyslaw -- Vielle, Anne -- Wang, Chengyang -- Whittle, Christina M -- Xue, Huiling -- Kingston, Robert E -- Kim, Ju Han -- Bernstein, Bradley E -- Dernburg, Abby F -- Pirrotta, Vincenzo -- Kuroda, Mitzi I -- Noble, William S -- Tullius, Thomas D -- Kellis, Manolis -- MacAlpine, David M -- Strome, Susan -- Elgin, Sarah C R -- Liu, Xiaole Shirley -- Lieb, Jason D -- Ahringer, Julie -- Karpen, Gary H -- Park, Peter J -- 092096/Wellcome Trust/United Kingdom -- 101863/Wellcome Trust/United Kingdom -- 54523/Wellcome Trust/United Kingdom -- 5RL9EB008539/EB/NIBIB NIH HHS/ -- K99 HG006259/HG/NHGRI NIH HHS/ -- K99HG006259/HG/NHGRI NIH HHS/ -- R01 GM098461/GM/NIGMS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R37 GM048405/GM/NIGMS NIH HHS/ -- T32 GM071340/GM/NIGMS NIH HHS/ -- T32 HG002295/HG/NHGRI NIH HHS/ -- U01 HG004258/HG/NHGRI NIH HHS/ -- U01 HG004270/HG/NHGRI NIH HHS/ -- U01 HG004279/HG/NHGRI NIH HHS/ -- U01 HG004695/HG/NHGRI NIH HHS/ -- U01HG004258/HG/NHGRI NIH HHS/ -- U01HG004270/HG/NHGRI NIH HHS/ -- U01HG004279/HG/NHGRI NIH HHS/ -- U01HG004695/HG/NHGRI NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54 HG004570/HG/NHGRI NIH HHS/ -- U54 HG006991/HG/NHGRI NIH HHS/ -- U54CA121852/CA/NCI NIH HHS/ -- U54HG004570/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Aug 28;512(7515):449-52. doi: 10.1038/nature13415.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] [4] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3]. ; 1] Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] [4] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Biology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Department of Information and Computer Engineering, Ajou University, Suwon 443-749, Korea [2] Systems Biomedical Informatics Research Center, College of Medicine, Seoul National University, Seoul 110-799, Korea. ; 1] Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA [2] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [3] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; The Gurdon Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. ; 1] National Institute of General Medical Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA [2] National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, USA. ; 1] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Broad Institute, Cambridge, Massachusetts 02141, USA [3] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130, USA [2] Victor Chang Cardiac Research Institute and The University of New South Wales, Sydney, New South Wales 2052, Australia (J.W.K.H.); Department of Biochemistry, University at Buffalo, Buffalo, New York 14203, USA (T.L.); Department of Molecular Biology and Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA (K.I., T.E.J.); Department of Human Genetics, University of Chicago, Chicago, Illinois 06037, USA (J.D.L.); Division of Genomic Technologies, Center for Life Science Technologies, RIKEN, Yokohama 230-0045, Japan (A.M.); Department of Genetics, Department of Computer Science, Stanford University, Stanford, California 94305, USA (A.K.); Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA (N.C.R.). ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Program in Bioinformatics, Boston University, Boston, Massachusetts 02215, USA. ; Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064, USA. ; Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China. ; 1] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA [2] Food Science and Technology Department, Faculty of Agriculture, Alexandria University, 21545 El-Shatby, Alexandria, Egypt. ; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Department of Biology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Harvard/MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA. ; Department of Anatomy Physiology and Cell Biology, University of California Davis, Davis, California 95616, USA. ; Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Department of Biology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [2] Department of Biology, Center for Genomics and Systems Biology, New York University, New York, New York 10003, USA. ; National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA. ; Princess Margaret Cancer Centre, Toronto, Ontario M6G 1L7, Canada. ; 1] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. ; 1] Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA [2] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA. ; Department of Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA. ; Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Lab, Berkeley, California 94720, USA [2] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [3] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA. ; 1] Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA [2] Department of Molecular Biology, Umea University, 901 87 Umea, Sweden. ; 1] Systems Biomedical Informatics Research Center, College of Medicine, Seoul National University, Seoul 110-799, Korea [2] Seoul National University Biomedical Informatics, Division of Biomedical Informatics, College of Medicine, Seoul National University, Seoul 110-799, Korea. ; 1] Broad Institute, Cambridge, Massachusetts 02141, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA [3] Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA. ; 1] Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA [2] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; 1] Program in Bioinformatics, Boston University, Boston, Massachusetts 02215, USA [2] Department of Chemistry, Boston University, Boston, Massachusetts 02215, USA. ; 1] Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Broad Institute, Cambridge, Massachusetts 02141, USA. ; 1] Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Informatics Program, Children's Hospital, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25164756" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*cytology/*genetics ; Cell Line ; Centromere/genetics/metabolism ; Chromatin/chemistry/*genetics/*metabolism ; Chromatin Assembly and Disassembly/genetics ; DNA Replication/genetics ; Drosophila melanogaster/*cytology/*genetics ; Enhancer Elements, Genetic/genetics ; Epigenesis, Genetic ; Heterochromatin/chemistry/genetics/metabolism ; Histones/chemistry/metabolism ; Humans ; Molecular Sequence Annotation ; Nuclear Lamina/metabolism ; Nucleosomes/chemistry/genetics/metabolism ; Promoter Regions, Genetic/genetics ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2013-11-29
    Description: Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940870/" 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/PMC3940870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNamara, Case W -- Lee, Marcus C S -- Lim, Chek Shik -- Lim, Siau Hoi -- Roland, Jason -- Nagle, Advait -- Simon, Oliver -- Yeung, Bryan K S -- Chatterjee, Arnab K -- McCormack, Susan L -- Manary, Micah J -- Zeeman, Anne-Marie -- Dechering, Koen J -- Kumar, T R Santha -- Henrich, Philipp P -- Gagaring, Kerstin -- Ibanez, Maureen -- Kato, Nobutaka -- Kuhen, Kelli L -- Fischli, Christoph -- Rottmann, Matthias -- Plouffe, David M -- Bursulaya, Badry -- Meister, Stephan -- Rameh, Lucia -- Trappe, Joerg -- Haasen, Dorothea -- Timmerman, Martijn -- Sauerwein, Robert W -- Suwanarusk, Rossarin -- Russell, Bruce -- Renia, Laurent -- Nosten, Francois -- Tully, David C -- Kocken, Clemens H M -- Glynne, Richard J -- Bodenreider, Christophe -- Fidock, David A -- Diagana, Thierry T -- Winzeler, Elizabeth A -- 078285/Wellcome Trust/United Kingdom -- 089275/Wellcome Trust/United Kingdom -- 090534/Wellcome Trust/United Kingdom -- 096157/Wellcome Trust/United Kingdom -- R01 AI079709/AI/NIAID NIH HHS/ -- R01 AI085584/AI/NIAID NIH HHS/ -- R01 AI090141/AI/NIAID NIH HHS/ -- R01 AI103058/AI/NIAID NIH HHS/ -- R01079709/PHS HHS/ -- R01085584/PHS HHS/ -- R01AI090141/AI/NIAID NIH HHS/ -- WT078285/Wellcome Trust/United Kingdom -- WT096157/Wellcome Trust/United Kingdom -- England -- Nature. 2013 Dec 12;504(7479):248-53. doi: 10.1038/nature12782. Epub 2013 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2]. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2]. ; Novartis Institutes for Tropical Disease, 138670 Singapore. ; Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA. ; Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA. ; Department of Parasitology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH Rijswijk, The Netherlands. ; TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands. ; Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA. ; Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland. ; 1] Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland [2] University of Basel, CH-4003 Basel, Switzerland. ; Department of Medicine, School of Medicine, Boston University, Boston, Massachusetts 02118, USA. ; Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. ; 1] TropIQ Health Sciences, 6525 GA Nijmegen, The Netherlands [2] Department of Medical Microbiology, Radboud University, Nijmegen Medical CentrePO Box 9101, 6500 HB Nijmegen, The Netherlands. ; Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore. ; 1] Laboratory of Malaria Immunobiology, Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Biopolis, 138648 Singapore [2] Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 117545 Singapore. ; 1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK [2] Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand. ; 1] Department of Microbiology & Immunology, Columbia University Medical Center, New York, New York 10032, USA [2] Division of Infectious Diseases, Department of Medicine, Columbia University Medical Center, New York, New York 10032, USA. ; 1] Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA [2] Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24284631" target="_blank"〉PubMed〈/a〉
    Keywords: 1-Phosphatidylinositol 4-Kinase/*antagonists & ; inhibitors/chemistry/genetics/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Cytokinesis/drug effects ; Drug Resistance/drug effects/genetics ; Fatty Acids/metabolism ; Female ; Hepatocytes/parasitology ; Humans ; Imidazoles/metabolism/pharmacology ; Life Cycle Stages/drug effects ; Macaca mulatta ; Malaria/*drug therapy/*parasitology ; Male ; Models, Biological ; Models, Molecular ; Phosphatidylinositol Phosphates/metabolism ; Plasmodium/classification/*drug effects/*enzymology/growth & development ; Pyrazoles/metabolism/pharmacology ; Quinoxalines/metabolism/pharmacology ; Reproducibility of Results ; Schizonts/cytology/drug effects ; rab GTP-Binding Proteins/genetics/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2011-02-05
    Description: X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals ( approximately 200 nm to 2 mum in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429598/" 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/PMC3429598/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapman, Henry N -- Fromme, Petra -- Barty, Anton -- White, Thomas A -- Kirian, Richard A -- Aquila, Andrew -- Hunter, Mark S -- Schulz, Joachim -- DePonte, Daniel P -- Weierstall, Uwe -- Doak, R Bruce -- Maia, Filipe R N C -- Martin, Andrew V -- Schlichting, Ilme -- Lomb, Lukas -- Coppola, Nicola -- Shoeman, Robert L -- Epp, Sascha W -- Hartmann, Robert -- Rolles, Daniel -- Rudenko, Artem -- Foucar, Lutz -- Kimmel, Nils -- Weidenspointner, Georg -- Holl, Peter -- Liang, Mengning -- Barthelmess, Miriam -- Caleman, Carl -- Boutet, Sebastien -- Bogan, Michael J -- Krzywinski, Jacek -- Bostedt, Christoph -- Bajt, Sasa -- Gumprecht, Lars -- Rudek, Benedikt -- Erk, Benjamin -- Schmidt, Carlo -- Homke, Andre -- Reich, Christian -- Pietschner, Daniel -- Struder, Lothar -- Hauser, Gunter -- Gorke, Hubert -- Ullrich, Joachim -- Herrmann, Sven -- Schaller, Gerhard -- Schopper, Florian -- Soltau, Heike -- Kuhnel, Kai-Uwe -- Messerschmidt, Marc -- Bozek, John D -- Hau-Riege, Stefan P -- Frank, Matthias -- Hampton, Christina Y -- Sierra, Raymond G -- Starodub, Dmitri -- Williams, Garth J -- Hajdu, Janos -- Timneanu, Nicusor -- Seibert, M Marvin -- Andreasson, Jakob -- Rocker, Andrea -- Jonsson, Olof -- Svenda, Martin -- Stern, Stephan -- Nass, Karol -- Andritschke, Robert -- Schroter, Claus-Dieter -- Krasniqi, Faton -- Bott, Mario -- Schmidt, Kevin E -- Wang, Xiaoyu -- Grotjohann, Ingo -- Holton, James M -- Barends, Thomas R M -- Neutze, Richard -- Marchesini, Stefano -- Fromme, Raimund -- Schorb, Sebastian -- Rupp, Daniela -- Adolph, Marcus -- Gorkhover, Tais -- Andersson, Inger -- Hirsemann, Helmut -- Potdevin, Guillaume -- Graafsma, Heinz -- Nilsson, Bjorn -- Spence, John C H -- 1R01GM095583-01/GM/NIGMS NIH HHS/ -- 1U54GM094625-01/GM/NIGMS NIH HHS/ -- R01 GM095583/GM/NIGMS NIH HHS/ -- U54 GM094599/GM/NIGMS NIH HHS/ -- U54 GM094625/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Feb 3;470(7332):73-7. doi: 10.1038/nature09750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Free-Electron Laser Science, DESY, Notkestrasse 85, 22607 Hamburg, Germany. henry.chapman@desy.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21293373" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray/instrumentation/*methods ; Lasers ; Models, Molecular ; Nanoparticles/*chemistry ; Nanotechnology/instrumentation/*methods ; Photosystem I Protein Complex/*chemistry ; Protein Conformation ; Time Factors ; X-Rays
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    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2011-03-25
    Description: Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-kappaB signalling was indicated by mutations in 11 members of the NF-kappaB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560292/" 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/PMC3560292/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapman, Michael A -- Lawrence, Michael S -- Keats, Jonathan J -- Cibulskis, Kristian -- Sougnez, Carrie -- Schinzel, Anna C -- Harview, Christina L -- Brunet, Jean-Philippe -- Ahmann, Gregory J -- Adli, Mazhar -- Anderson, Kenneth C -- Ardlie, Kristin G -- Auclair, Daniel -- Baker, Angela -- Bergsagel, P Leif -- Bernstein, Bradley E -- Drier, Yotam -- Fonseca, Rafael -- Gabriel, Stacey B -- Hofmeister, Craig C -- Jagannath, Sundar -- Jakubowiak, Andrzej J -- Krishnan, Amrita -- Levy, Joan -- Liefeld, Ted -- Lonial, Sagar -- Mahan, Scott -- Mfuko, Bunmi -- Monti, Stefano -- Perkins, Louise M -- Onofrio, Robb -- Pugh, Trevor J -- Rajkumar, S Vincent -- Ramos, Alex H -- Siegel, David S -- Sivachenko, Andrey -- Stewart, A Keith -- Trudel, Suzanne -- Vij, Ravi -- Voet, Douglas -- Winckler, Wendy -- Zimmerman, Todd -- Carpten, John -- Trent, Jeff -- Hahn, William C -- Garraway, Levi A -- Meyerson, Matthew -- Lander, Eric S -- Getz, Gad -- Golub, Todd R -- K12 CA133250/CA/NCI NIH HHS/ -- R01 AG020686/AG/NIA NIH HHS/ -- R01 AG020686-07/AG/NIA NIH HHS/ -- R01 CA133115/CA/NCI NIH HHS/ -- R01 CA133115-04/CA/NCI NIH HHS/ -- R01 CA133966/CA/NCI NIH HHS/ -- R01 CA133966-03/CA/NCI NIH HHS/ -- England -- Nature. 2011 Mar 24;471(7339):467-72. doi: 10.1038/nature09837.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02412, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21430775" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Blood Coagulation/genetics ; CpG Islands/genetics ; DNA Mutational Analysis ; DNA Repair/genetics ; Exons/genetics ; Exosome Multienzyme Ribonuclease Complex ; Genome, Human/*genetics ; Genomics ; Histones/metabolism ; Homeodomain Proteins/genetics ; Homeostasis/genetics ; Humans ; Methylation ; Models, Molecular ; Molecular Sequence Data ; Multiple Myeloma/drug therapy/enzymology/*genetics/metabolism ; Mutation/*genetics ; NF-kappa B/metabolism ; Oncogenes/genetics ; Open Reading Frames/genetics ; Protein Biosynthesis/genetics ; Protein Conformation ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors/genetics/metabolism ; RNA Processing, Post-Transcriptional/genetics ; Ribonucleases/chemistry/genetics ; Signal Transduction/genetics ; Transcription, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2014-04-04
    Description: Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bind in the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gad, Helge -- Koolmeister, Tobias -- Jemth, Ann-Sofie -- Eshtad, Saeed -- Jacques, Sylvain A -- Strom, Cecilia E -- Svensson, Linda M -- Schultz, Niklas -- Lundback, Thomas -- Einarsdottir, Berglind Osk -- Saleh, Aljona -- Gokturk, Camilla -- Baranczewski, Pawel -- Svensson, Richard -- Berntsson, Ronnie P-A -- Gustafsson, Robert -- Stromberg, Kia -- Sanjiv, Kumar -- Jacques-Cordonnier, Marie-Caroline -- Desroses, Matthieu -- Gustavsson, Anna-Lena -- Olofsson, Roger -- Johansson, Fredrik -- Homan, Evert J -- Loseva, Olga -- Brautigam, Lars -- Johansson, Lars -- Hoglund, Andreas -- Hagenkort, Anna -- Pham, Therese -- Altun, Mikael -- Gaugaz, Fabienne Z -- Vikingsson, Svante -- Evers, Bastiaan -- Henriksson, Martin -- Vallin, Karl S A -- Wallner, Olov A -- Hammarstrom, Lars G J -- Wiita, Elisee -- Almlof, Ingrid -- Kalderen, Christina -- Axelsson, Hanna -- Djureinovic, Tatjana -- Puigvert, Jordi Carreras -- Haggblad, Maria -- Jeppsson, Fredrik -- Martens, Ulf -- Lundin, Cecilia -- Lundgren, Bo -- Granelli, Ingrid -- Jensen, Annika Jenmalm -- Artursson, Per -- Nilsson, Jonas A -- Stenmark, Pal -- Scobie, Martin -- Berglund, Ulrika Warpman -- Helleday, Thomas -- England -- Nature. 2014 Apr 10;508(7495):215-21. doi: 10.1038/nature13181. Epub 2014 Apr 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2]. ; Department of Biochemistry and Biophysics, Stockholm University, S-106 91 Stockholm, Sweden. ; Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden. ; 1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Chemical Biology Consortium Sweden, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden. ; Sahlgrenska Translational Melanoma Group, Sahlgrenska Cancer Center, Department of Surgery, University of Gothenburg and Sahlgrenska University Hospital, S-405 30 Gothenburg, Sweden. ; Department of Analytical Chemistry, Stockholm University, S-106 91 Stockholm, Sweden. ; 1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Department of Pharmacy, Uppsala University, S-751 23 Uppsala, Sweden. ; 1] Chemical Biology Consortium Sweden, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Uppsala University Drug Optimization and Pharmaceutical Profiling Platform, Department of Pharmacy, Uppsala University, S-751 23 Uppsala, Sweden. ; Department of Genetics, Microbiology and Toxicology, Stockholm University, S-106 91 Stockholm, Sweden. ; 1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Clinical Pharmacology, Department of Medical and Health Sciences, Linkoping University, S-58185 Linkoping, Sweden. ; 1] Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden [2] Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1006 Amsterdam, The Netherlands (B.E.); Department of Immunology, Genetics, and Pathology, Uppsala University, S-751 23 Uppsala, Sweden (T.D.). ; 1] Department of Genetics, Microbiology and Toxicology, Stockholm University, S-106 91 Stockholm, Sweden [2] Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1006 Amsterdam, The Netherlands (B.E.); Department of Immunology, Genetics, and Pathology, Uppsala University, S-751 23 Uppsala, Sweden (T.D.). ; Science for Life Laboratory, RNAi Cell Screening Facility, Department of Biochemistry and Biophysics, Stockholm University, S-106 91 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695224" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalytic Domain ; Cell Death/drug effects ; Cell Survival/drug effects ; Crystallization ; DNA Damage ; DNA Repair Enzymes/*antagonists & inhibitors/chemistry/metabolism ; Deoxyguanine Nucleotides/metabolism ; Enzyme Inhibitors/chemistry/pharmacokinetics/pharmacology/therapeutic use ; Female ; Humans ; Male ; Mice ; Models, Molecular ; Molecular Conformation ; Molecular Targeted Therapy ; Neoplasms/*drug therapy/*metabolism/pathology ; Nucleotides/*metabolism ; Oxidation-Reduction/drug effects ; Phosphoric Monoester Hydrolases/*antagonists & inhibitors/chemistry/metabolism ; Pyrimidines/chemistry/pharmacokinetics/pharmacology/therapeutic use ; Pyrophosphatases/antagonists & inhibitors ; Reproducibility of Results ; Xenograft Model Antitumor Assays
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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