TABLE OF CONTENTS
| December 2015 Volume 47, Issue 12 |  | | |  |  Editorial
Obituary
News and Views
Perspective
Analysis
Brief Communications
Articles
Letters
| | | Advertisement | | | | Nature Reviews Molecular Cell Biology
FREE POSTER - Stem cell states: naive to primed pluripotency
This Poster provides an overview of the signalling pathways currently known to promote or suppress the naive and primed pluripotency states in mice, and highlights potential differences between mice and humans. It also provides an overview of culture conditions that confer naive and/or primed features to cells.
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| | | | | | Advertisement |  | | | | | | Editorial |  Top | |  | | Key mendelian variants p1371
doi:10.1038/ng.3463
| | Obituary | Top | | | | William Martin Gelbart 1945-2015 p1372
Kristi Wharton
doi:10.1038/ng.3455
| | News and Views | Top | | | | | | Perspective | Top | | | | Multisystem Lewy body disease and the other parkinsonian disorders pp1378 - 1384
J William Langston, Birgitt Schüle, Linda Rees, R Jeremy Nichols & Carrolee Barlow
doi:10.1038/ng.3454
Carrolee Barlow, J. William Langston, Birgitt Schüle and colleagues review the current classification of parkinsonian disorders. They propose the term 'multisystem Lewy body disease' to encompass three genetic subtypes of Parkinson's disease and distinguish this from other non–Lewy body parkinsonian disorders.
| | Analysis | Top | | | | Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis pp1385 - 1392
Po-Ru Loh, Gaurav Bhatia, Alexander Gusev, Hilary K Finucane, Brendan K Bulik-Sullivan, Samuela J Pollack, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Teresa R de Candia, Sang Hong Lee, Naomi R Wray, Kenneth S Kendler, Michael C O'Donovan, Benjamin M Neale, Nick Patterson & Alkes L Price
doi:10.1038/ng.3431
Po-Ru Loh, Alkes Price and colleagues developed a fast algorithm for multicomponent, multi-trait variance-components analysis and use it to analyze the genetic architectures of schizophrenia and nine complex diseases from the PGC and GERA cohorts. Their analyses support a largely polygenic architecture for schizophrenia and significant genetic correlations for several pairs of GERA diseases.
| | | | Large-scale identification of sequence variants influencing human transcription factor occupancy in vivo pp1393 - 1401
Matthew T Maurano, Eric Haugen, Richard Sandstrom, Jeff Vierstra, Anthony Shafer, Rajinder Kaul & John A Stamatoyannopoulos
doi:10.1038/ng.3432
Matthew Maurano, John Stamatoyannopoulos and colleagues identify 64,597 allelically imbalanced SNPs that influence transcription factor occupancy in vivo. Using these data, they develop a general scoring method to identify regulatory variants likely to affect transcription factor occupancy in the human genome.
| | | | Clock-like mutational processes in human somatic cells pp1402 - 1407
Ludmil B Alexandrov, Philip H Jones, David C Wedge, Julian E Sale, Peter J Campbell, Serena Nik-Zainal & Michael R Stratton
doi:10.1038/ng.3441
Ludmil Alexandrov, Michael Stratton and colleagues analyze 10,250 human cancer genomes from 36 cancer types to identify mutational signatures with clock-like properties. They identify two signatures with different mutation rates that show a correlation between age at diagnosis and number of mutations in most cancer types.
| | Brief Communications | Top | | | | Recurrent inactivating RASA2 mutations in melanoma pp1408 - 1410
Rand Arafeh, Nouar Qutob, Rafi Emmanuel, Alona Keren-Paz, Jason Madore, Abdel Elkahloun, James S Wilmott, Jared J Gartner, Antonella Di Pizio, Sabina Winograd-Katz, Sivasish Sindiri, Ron Rotkopf, Ken Dutton-Regester, Peter Johansson, Antonia L Pritchard, Nicola Waddell, Victoria K Hill, Jimmy C Lin, Yael Hevroni, Steven A Rosenberg, Javed Khan, Shifra Ben-Dor, Masha Y Niv, Igor Ulitsky, Graham J Mann, Richard A Scolyer, Nicholas K Hayward & Yardena Samuels
doi:10.1038/ng.3427
Yardena Samuels and colleagues report the analysis of 501 melanoma exomes and the identification of RASA2 as a tumor-suppressor gene mutated in 5% of melanomas. RASA2 mutations led to increased RAS activation, and RASA2 loss was associated with shorter patient survival times.
| | | | TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors pp1411 - 1414
Linda J Valentijn, Jan Koster, Danny A Zwijnenburg, Nancy E Hasselt, Peter van Sluis, Richard Volckmann, Max M van Noesel, Rani E George, Godelieve A M Tytgat, Jan J Molenaar & Rogier Versteeg
doi:10.1038/ng.3438
Rogier Versteeg and colleagues analyze the whole-genome sequences of 108 neuroblastoma samples and detect structural rearrangements of TERT in 23% of high-stage cases. TERT rearrangements are associated with increased TERT expression, increased telomere length and very poor prognosis.
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REGISTER NOW |  | | | | | | Articles | Top | | | | Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci pp1415 - 1425
Kyle J Gaulton, Teresa Ferreira, Yeji Lee, Anne Raimondo, Reedik Mägi, Michael E Reschen, Anubha Mahajan, Adam Locke, N William Rayner, Neil Robertson, Robert A Scott, Inga Prokopenko, Laura J Scott, Todd Green, Thomas Sparso, Dorothee Thuillier, Loic Yengo, Harald Grallert, Simone Wahl, Mattias Frånberg, Rona J Strawbridge, Hans Kestler, Himanshu Chheda, Lewin Eisele, Stefan Gustafsson, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, Lu Qi, Lennart C Karssen, Elisabeth M van Leeuwen, Sara M Willems, Man Li, Han Chen, Christian Fuchsberger, Phoenix Kwan, Clement Ma, Michael Linderman, Yingchang Lu, Soren K Thomsen, Jana K Rundle, Nicola L Beer, Martijn van de Bunt, Anil Chalisey, Hyun Min Kang, Benjamin F Voight, Gonçalo R Abecasis, Peter Almgren, Damiano Baldassarre, Beverley Balkau, Rafn Benediktsson, Matthias Blüher, Heiner Boeing, Lori L Bonnycastle, Erwin P Bottinger, Noël P Burtt, Jason Carey, Guillaume Charpentier, Peter S Chines, Marilyn C Cornelis, David J Couper, Andrew T Crenshaw, Rob M van Dam, Alex S F Doney, Mozhgan Dorkhan, Sarah Edkins, Johan G Eriksson, Tonu Esko, Elodie Eury, João Fadista, Jason Flannick, Pierre Fontanillas, Caroline Fox, Paul W Franks, Karl Gertow, Christian Gieger, Bruna Gigante, Omri Gottesman, George B Grant, Niels Grarup, Christopher J Groves, Maija Hassinen, Christian T Have, Christian Herder, Oddgeir L Holmen, Astradur B Hreidarsson, Steve E Humphries, David J Hunter, Anne U Jackson, Anna Jonsson, Marit E Jørgensen, Torben Jørgensen, Wen-Hong L Kao, Nicola D Kerrison, Leena Kinnunen, Norman Klopp, Augustine Kong, Peter Kovacs, Peter Kraft, Jasmina Kravic, Cordelia Langford, Karin Leander, Liming Liang, Peter Lichtner, Cecilia M Lindgren, Eero Lindholm, Allan Linneberg, Ching-Ti Liu, Stéphane Lobbens, Jian'an Luan, Valeriya Lyssenko, Satu Männistö, Olga McLeod, Julia Meyer, Evelin Mihailov, Ghazala Mirza, Thomas W Mühleisen, Martina Müller-Nurasyid, Carmen Navarro, Markus M Nöthen, Nikolay N Oskolkov, Katharine R Owen, Domenico Palli, Sonali Pechlivanis, Leena Peltonen, John R B Perry, Carl G P Platou, Michael Roden, Douglas Ruderfer, Denis Rybin, Yvonne T van der Schouw, Bengt Sennblad, Gunnar Sigurðsson, Alena Stančáková, Gerald Steinbach, Petter Storm, Konstantin Strauch, Heather M Stringham, Qi Sun, Barbara Thorand, Emmi Tikkanen, Anke Tonjes, Joseph Trakalo, Elena Tremoli, Tiinamaija Tuomi, Roman Wennauer, Steven Wiltshire, Andrew R Wood, Eleftheria Zeggini, Ian Dunham, Ewan Birney, Lorenzo Pasquali, Jorge Ferrer, Ruth J F Loos, Josée Dupuis, Jose C Florez, Eric Boerwinkle, James S Pankow, Cornelia van Duijn, Eric Sijbrands, James B Meigs, Frank B Hu, Unnur Thorsteinsdottir, Kari Stefansson, Timo A Lakka, Rainer Rauramaa, Michael Stumvoll, Nancy L Pedersen, Lars Lind, Sirkka M Keinanen-Kiukaanniemi, Eeva Korpi-Hyövälti, Timo E Saaristo, Juha Saltevo, Johanna Kuusisto, Markku Laakso, Andres Metspalu, Raimund Erbel, Karl-Heinz Jöcke, Susanne Moebus, Samuli Ripatti, Veikko Salomaa, Erik Ingelsson, Bernhard O Boehm, Richard N Bergman, Francis S Collins, Karen L Mohlke, Heikki Koistinen, Jaakko Tuomilehto, Kristian Hveem, Inger Njølstad, Panagiotis Deloukas, Peter J Donnelly, Timothy M Frayling, Andrew T Hattersley, Ulf de Faire, Anders Hamsten, Thomas Illig, Annette Peters, Stephane Cauchi, Rob Sladek, Philippe Froguel, Torben Hansen, Oluf Pedersen, Andrew D Morris, Collin N A Palmer, Sekar Kathiresan, Olle Melander, Peter M Nilsson, Leif C Groop, Inês Barroso, Claudia Langenberg, Nicholas J Wareham, Christopher A O'Callaghan, Anna L Gloyn, David Altshuler, Michael Boehnke, Tanya M Teslovich, Mark I McCarthy, Andrew P Morris & the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
doi:10.1038/ng.3437
Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.
See also: News and Views by Polychronakos & Alriyami | | | | Genomic profiling of Sezary syndrome identifies alterations of key T cell signaling and differentiation genes pp1426 - 1434
Linghua Wang, Xiao Ni, Kyle R Covington, Betty Y Yang, Jessica Shiu, Xiang Zhang, Liu Xi, Qingchang Meng, Timothy Langridge, Jennifer Drummond, Lawrence A Donehower, Harshavardhan Doddapaneni, Donna M Muzny, Richard A Gibbs, David A Wheeler & Madeleine Duvic
doi:10.1038/ng.3444
Madeleine Duvic, David Wheeler and colleagues present an integrated genomic analysis of Sezary syndrome. They identify recurrent alterations in key T cell signaling and differentiation genes and observe overexpression of IL32 and IL2RG in nearly all cases.
| | | | The pineapple genome and the evolution of CAM photosynthesis OPEN pp1435 - 1442
Ray Ming, Robert VanBuren, Ching Man Wai, Haibao Tang, Michael C Schatz, John E Bowers, Eric Lyons, Ming-Li Wang, Jung Chen, Eric Biggers, Jisen Zhang, Lixian Huang, Lingmao Zhang, Wenjing Miao, Jian Zhang, Zhangyao Ye, Chenyong Miao, Zhicong Lin, Hao Wang, Hongye Zhou, Won C Yim, Henry D Priest, Chunfang Zheng, Margaret Woodhouse, Patrick P Edger, Romain Guyot, Hao-Bo Guo, Hong Guo, Guangyong Zheng, Ratnesh Singh, Anupma Sharma, Xiangjia Min, Yun Zheng, Hayan Lee, James Gurtowski, Fritz J Sedlazeck, Alex Harkess, Michael R McKain, Zhenyang Liao, Jingping Fang, Juan Liu, Xiaodan Zhang, Qing Zhang, Weichang Hu, Yuan Qin, Kai Wang, Li-Yu Chen, Neil Shirley, Yann-Rong Lin, Li-Yu Liu, Alvaro G Hernandez, Chris L Wright, Vincent Bulone, Gerald A Tuskan, Katy Heath, Francis Zee, Paul H Moore, Ramanjulu Sunkar, James H Leebens-Mack, Todd Mockler, Jeffrey L Bennetzen, Michael Freeling, David Sankoff, Andrew H Paterson, Xinguang Zhu, Xiaohan Yang, J Andrew C Smith, John C Cushman, Robert E Paull & Qingyi Yu
doi:10.1038/ng.3435
Ray Ming, Robert Paull, Qingyi Yu and colleagues report the genome sequences of two cultivated pineapple varieties and one wild pineapple relative. Their analysis supports the use of the pineapple as a reference genome for monocot comparative genomics and provides insight into the evolution of crassulacean acid metabolism photosynthesis.
See also: News and Views by Xu & Liu | | Letters | Top | | | | A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis pp1443 - 1448
Stephan Buch, Felix Stickel, Eric Trépo, Michael Way, Alexander Herrmann, Hans Dieter Nischalke, Mario Brosch, Jonas Rosendahl, Thomas Berg, Monika Ridinger, Marcella Rietschel, Andrew McQuillin, Josef Frank, Falk Kiefer, Stefan Schreiber, Wolfgang Lieb, Michael Soyka, Nasser Semmo, Elmar Aigner, Christian Datz, Renate Schmelz, Stefan Brückner, Sebastian Zeissig, Anna-Magdalena Stephan, Norbert Wodarz, Jacques Devière, Nicolas Clumeck, Christoph Sarrazin, Frank Lammert, Thierry Gustot, Pierre Deltenre, Henry Völzke, Markus M Lerch, Julia Mayerle, Florian Eyer, Clemens Schafmayer, Sven Cichon, Markus M Nöthen, Michael Nothnagel, David Ellinghaus, Klaus Huse, Andre Franke, Steffen Zopf, Claus Hellerbrand, Christophe Moreno, Denis Franchimont, Marsha Y Morgan & Jochen Hampe
doi:10.1038/ng.3417
Felix Stickel and colleagues report the results of a genome-wide association study of alcohol-related cirrhosis. They confirm PNPLA3 as a susceptibility locus and identify new association signals in MBOAT7 and TM6SF2.
| | | | Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis pp1449 - 1456
Lavinia Paternoster, Marie Standl, Johannes Waage, Hansjörg Baurecht, Melanie Hotze, David P Strachan, John A Curtin, Klaus Bønnelykke, Chao Tian, Atsushi Takahashi, Jorge Esparza-Gordillo, Alexessander Couto Alves, Jacob P Thyssen, Herman T den Dekker, Manuel A Ferreira, Elisabeth Altmaier, Patrick M A Sleiman, Feng Li Xiao, Juan R Gonzalez, Ingo Marenholz, Birgit Kalb, Maria Pino-Yanes, Cheng-Jian Xu, Lisbeth Carstensen, Maria M Groen-Blokhuis, Cristina Venturini, Craig E Pennell, Sheila J Barton, Albert M Levin, Ivan Curjuric, Mariona Bustamante, Eskil Kreiner-Møller, Gabrielle A Lockett, Jonas Bacelis, Supinda Bunyavanich, Rachel A Myers, Anja Matanovic, Ashish Kumar, Joyce Y Tung, Tomomitsu Hirota, Michiaki Kubo, Wendy L McArdle, A John Henderson, John P Kemp, Jie Zheng, George Davey Smith, Franz Rüschendorf, Anja Bauerfeind, Min Ae Lee-Kirsch, Andreas Arnold, Georg Homuth, Carsten O Schmidt, Elisabeth Mangold, Sven Cichon, Thomas Keil, Elke Rodríguez, Annette Peters, Andre Franke, Wolfgang Lieb, Natalija Novak, Regina Fölster-Holst, Momoko Horikoshi, Juha Pekkanen, Sylvain Sebert, Lise L Husemoen, Niels Grarup, Johan C de Jongste, Fernando Rivadeneira, Albert Hofman, Vincent W V Jaddoe, Suzanne G M A Pasmans, Niels J Elbert, André G Uitterlinden, Guy B Marks, Philip J Thompson, Melanie C Matheson, Colin F Robertson, Australian Asthma Genetics Consortium(AAGC), Janina S Ried, Jin Li, Xian Bo Zuo, Xiao Dong Zheng, Xian Yong Yin, Liang Dan Sun, Maeve A McAleer, Grainne M O'Regan, Caoimhe M R Fahy, Linda E Campbell, Milan Macek, Michael Kurek, Donglei Hu, Celeste Eng, Dirkje S Postma, Bjarke Feenstra, Frank Geller, Jouke Jan Hottenga, Christel M Middeldorp, Pirro Hysi, Veronique Bataille, Tim Spector, Carla M T Tiesler, Elisabeth Thiering, Badri Pahukasahasram, James J Yang, Medea Imboden, Scott Huntsman, Natàlia Vilor-Tejedor, Caroline L Relton, Ronny Myhre, Wenche Nystad, Adnan Custovic, Scott T Weiss, Deborah A Meyers, Cilla Söderhäll, Erik Melén, Carole Ober, Benjamin A Raby, Angela Simpson, Bo Jacobsson, John W Holloway, Hans Bisgaard, Jordi Sunyer, Nicole M Probst-Hensch, L Keoki Williams, Keith M Godfrey, Carol A Wang, Dorret I Boomsma, Mads Melbye, Gerard H Koppelman, Deborah Jarvis, W H Irwin McLean, Alan D Irvine, Xue Jun Zhang, Hakon Hakonarson, Christian Gieger, Esteban G Burchard, Nicholas G Martin, Liesbeth Duijts, Allan Linneberg, Marjo-Riitta Jarvelin, Markus M Nöthen, Susanne Lau, Norbert Hübner, Young-Ae Lee, Mayumi Tamari, David A Hinds, Daniel Glass, Sara J Brown, Joachim Heinrich, David M Evans & Stephan Weidinger for the EArly Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium
doi:10.1038/ng.3424
Lavinia Paternoster and colleagues report the results of a large, multi-ancestry genome-wide association study of atopic dermatitis. They identify ten new susceptibility loci harboring candidate genes involved in innate host defense and T cell function.
| | | | Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus pp1457 - 1464
James Bentham, David L Morris, Deborah S Cunninghame Graham, Christopher L Pinder, Philip Tombleson, Timothy W Behrens, Javier Martín, Benjamin P Fairfax, Julian C Knight, Lingyan Chen, Joseph Replogle, Ann-Christine Syvänen, Lars Rönnblom, Robert R Graham, Joan E Wither, John D Rioux, Marta E Alarcón-Riquelme & Timothy J Vyse
doi:10.1038/ng.3434
Timothy Vyse and colleagues report the results of a large-scale association study of systemic lupus erythematosus (SLE). They identify ten new susceptibility loci and implicate aberrant regulation of innate and adaptive immunity genes in disease pathogenesis.
| | | | The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome pp1465 - 1470
Ana Carolina da Silva Almeida, Francesco Abate, Hossein Khiabanian, Estela Martinez-Escala, Joan Guitart, Cornelis P Tensen, Maarten H Vermeer, Raul Rabadan, Adolfo Ferrando & Teresa Palomero
doi:10.1038/ng.3442
Teresa Palomero, Adolfo Ferrando, Raul Rabadan and colleagues report the results of an exome sequencing study of cutaneous T cell lymphoma (CTCL). They identify highly recurrent chromosomal deletions along with a broad spectrum of somatic mutations in genes involved in epigenetic regulation and signaling.
| | | | Mutations in the transcriptional repressor REST predispose to Wilms tumor pp1471 - 1474
Shazia S Mahamdallie, Sandra Hanks, Kristen L Karlin, Anna Zachariou, Elizabeth R Perdeaux, Elise Ruark, Chad A Shaw, Alexander Renwick, Emma Ramsay, Shawn Yost, Anna Elliott, Jillian Birch, Michael Capra, Juliet Gray, Juliet Hale, Judith Kingston, Gill Levitt, Thomas McLean, Eamonn Sheridan, Anthony Renwick, Sheila Seal, Charles Stiller, Neil Sebire, Thomas F Westbrook & Nazneen Rahman
doi:10.1038/ng.3440
Nazneen Rahman and colleagues identify inactivating germline mutations in the gene encoding the transcriptional repressor REST in familial and non-familial cases of Wilms tumor. The mutations cluster in the DNA-binding domain of REST and compromise REST transcriptional repression.
| | | | NRF2 regulates serine biosynthesis in non-small cell lung cancer pp1475 - 1481
Gina M DeNicola, Pei-Hsuan Chen, Edouard Mullarky, Jessica A Sudderth, Zeping Hu, David Wu, Hao Tang, Yang Xie, John M Asara, Kenneth E Huffman, Ignacio I Wistuba, John D Minna, Ralph J DeBerardinis & Lewis C Cantley
doi:10.1038/ng.3421
Lewis Cantley and colleagues report an integrated metabolic and transcriptomic study of non-small cell lung cancer (NSCLC) cell lines. They show that the activity of the serine/glycine biosynthetic pathway in NSCLC is highly heterogeneous and is regulated by NRF2 and that elevated expression of genes in this pathway confers poor prognosis in human NSCLC.
| | | | Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component pp1482 - 1488
Diane H Moon, Matthew Segal, Baris Boyraz, Eva Guinan, Inga Hofmann, Patrick Cahan, Albert K Tai & Suneet Agarwal
doi:10.1038/ng.3423
Suneet Agarwal and colleagues use somatic cells and induced pluripotent stem cells from patients with PARN mutations to show that PARN is required for the 3'-end maturation of the telomerase RNA component TERC. Their findings provide a mechanism linking PARN mutations to telomere diseases.
| | | | Seed filling in domesticated maize and rice depends on SWEET-mediated hexose transport pp1489 - 1493
Davide Sosso, Dangping Luo, Qin-Bao Li, Joelle Sasse, Jinliang Yang, Ghislaine Gendrot, Masaharu Suzuki, Karen E Koch, Donald R McCarty, Prem S Chourey, Peter M Rogowsky, Jeffrey Ross-Ibarra, Bing Yang & Wolf B Frommer
doi:10.1038/ng.3422
Davide Sosso and colleagues show that SWEET4 hexose transporters are essential for grain filling in both maize and rice, and were likely selected during domestication to enhance sugar import into the endosperm.
| | | | A recently evolved hexose transporter variant confers resistance to multiple pathogens in wheat pp1494 - 1498
John W Moore, Sybil Herrera-Foessel, Caixia Lan, Wendelin Schnippenkoetter, Michael Ayliffe, Julio Huerta-Espino, Morten Lillemo, Libby Viccars, Ricky Milne, Sambasivam Periyannan, Xiuying Kong, Wolfgang Spielmeyer, Mark Talbot, Harbans Bariana, John W Patrick, Peter Dodds, Ravi Singh & Evans Lagudah
doi:10.1038/ng.3439
Evans Lagudah and colleagues report that variation in a gene encoding a hexose transporter confers resistance to multiple pathogens in wheat. They further show that the variant protein encoded by the resistance allele exerts a dominant-negative effect by heterodimerizing with functional hexose transporters, resulting in reduced glucose uptake.
See also: News and Views by White & Frommer | | | Top | |  | | Advertisement | | Nature Insight: Precision Medicine
This Insight examines the emerging framework that is bringing together researchers, clinical laboratories, clinicians and patients in a precision-medicine ?ecosystem?, progress in pharmacogenomics and gene therapy towards personalized treatments, and the need to redesign clinical trials to match patients with the most suitable trial.
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