ALBERT

Description: OSIRIS-REx will return pristine samples of carbonaceous asteroid Bennu. This article describes how pristine was defined based on expectations of Bennu and on a realistic understanding of what is achievable with a constrained schedule and budget, and how that definition flowed to requirements and implementation. To return a pristine sample, the OSIRIS-REx spacecraft sampling hardware was maintained at level 100 A/2 and less than 180 ng/cm(exp 2) of amino acids and hydrazine on the sampler head through precision cleaning, control of materials, and vigilance. Contamination is further characterized via witness material exposed to the spacecraft assembly and testing environment as well as in space. This characterization provided knowledge of the expected background and will be used in conjunction with archived spacecraft components for comparison with the samples when they are delivered to Earth for analysis. Most of all, the cleanliness of the OSIRIS-REx spacecraft was achieved through communication among scientists, engineers, managers, and technicians.

Description: The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 x 10(-3) and 1.42 x 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Quick, Joshua -- Loman, Nicholas J -- Duraffour, Sophie -- Simpson, Jared T -- Severi, Ettore -- Cowley, Lauren -- Bore, Joseph Akoi -- Koundouno, Raymond -- Dudas, Gytis -- Mikhail, Amy -- Ouedraogo, Nobila -- Afrough, Babak -- Bah, Amadou -- Baum, Jonathan H J -- Becker-Ziaja, Beate -- Boettcher, Jan Peter -- Cabeza-Cabrerizo, Mar -- Camino-Sanchez, Alvaro -- Carter, Lisa L -- Doerrbecker, Juliane -- Enkirch, Theresa -- Garcia-Dorival, Isabel -- Hetzelt, Nicole -- Hinzmann, Julia -- Holm, Tobias -- Kafetzopoulou, Liana Eleni -- Koropogui, Michel -- Kosgey, Abigael -- Kuisma, Eeva -- Logue, Christopher H -- Mazzarelli, Antonio -- Meisel, Sarah -- Mertens, Marc -- Michel, Janine -- Ngabo, Didier -- Nitzsche, Katja -- Pallasch, Elisa -- Patrono, Livia Victoria -- Portmann, Jasmine -- Repits, Johanna Gabriella -- Rickett, Natasha Y -- Sachse, Andreas -- Singethan, Katrin -- Vitoriano, Ines -- Yemanaberhan, Rahel L -- Zekeng, Elsa G -- Racine, Trina -- Bello, Alexander -- Sall, Amadou Alpha -- Faye, Ousmane -- Faye, Oumar -- Magassouba, N'Faly -- Williams, Cecelia V -- Amburgey, Victoria -- Winona, Linda -- Davis, Emily -- Gerlach, Jon -- Washington, Frank -- Monteil, Vanessa -- Jourdain, Marine -- Bererd, Marion -- Camara, Alimou -- Somlare, Hermann -- Camara, Abdoulaye -- Gerard, Marianne -- Bado, Guillaume -- Baillet, Bernard -- Delaune, Deborah -- Nebie, Koumpingnin Yacouba -- Diarra, Abdoulaye -- Savane, Yacouba -- Pallawo, Raymond Bernard -- Gutierrez, Giovanna Jaramillo -- Milhano, Natacha -- Roger, Isabelle -- Williams, Christopher J -- Yattara, Facinet -- Lewandowski, Kuiama -- Taylor, James -- Rachwal, Phillip -- Turner, Daniel J -- Pollakis, Georgios -- Hiscox, Julian A -- Matthews, David A -- O'Shea, Matthew K -- Johnston, Andrew McD -- Wilson, Duncan -- Hutley, Emma -- Smit, Erasmus -- Di Caro, Antonino -- Wolfel, Roman -- Stoecker, Kilian -- Fleischmann, Erna -- Gabriel, Martin -- Weller, Simon A -- Koivogui, Lamine -- Diallo, Boubacar -- Keita, Sakoba -- Rambaut, Andrew -- Formenty, Pierre -- Gunther, Stephan -- Carroll, Miles W -- Medical Research Council/United Kingdom -- England -- Nature. 2016 Feb 11;530(7589):228-32. doi: 10.1038/nature16996. Epub 2016 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Microbiology and Infection, University of Birmingham, Birmingham B15 2TT, UK. ; The European Mobile Laboratory Consortium, Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; Bernhard-Nocht-Institute for Tropical Medicine, D-20359 Hamburg, Germany. ; Ontario Institute for Cancer Research, Toronto M5G 0A3, Canada. ; Department of Computer Science, University of Toronto, Toronto M5S 3G4, Canada. ; European Centre for Disease Prevention and Control (ECDC), 171 65 Solna, Sweden. ; National Infection Service, Public Health England, London NW9 5EQ, UK. ; Institute of Evolutionary Biology, University of Edinburgh, Edinburgh EH9 2FL, UK. ; Postgraduate Training for Applied Epidemiology (PAE, German FETP), Robert Koch Institute, D-13302 Berlin, Germany. ; National Infection Service, Public Health England, Porton Down, Wiltshire SP4 0JG, UK. ; Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland. ; Robert Koch Institute, D-13302 Berlin, Germany. ; University College London, London WC1E 6BT, UK. ; Paul-Ehrlich-Institut, Division of Veterinary Medicine, D-63225 Langen, Germany. ; Institute of Infection and Global Health, University of Liverpool, Liverpool L69 7BE, UK. ; Laboratory for Clinical and Epidemiological Virology, Department of Microbiology and Immunology, KU Leuven, Leuven B-3000, Belgium. ; Ministry of Health Guinea, Conakry BP 585, Guinea. ; Kenya Medical Research Institute, Nairobi P.O. BOX 54840 - 00200, Kenya. ; National Institute for Infectious Diseases L. Spallanzani, 00149 Rome, Italy. ; Friedrich-Loeffler-Institute, D-17493 Greifswald, Germany. ; Federal Office for Civil Protection, Spiez Laboratory, 3700 Spiez, Switzerland. ; Janssen-Cilag, Stockholm, Box 7073 - 19207, Sweden. ; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool L69 7BE, UK. ; Institute of Virology, Technische Universitat Munchen, D-81675 Munich, Germany. ; Public Health Agency of Canada, Winnipeg, Manitoba R3E 3R2, Canada. ; Institut Pasteur Dakar, Dakar, DP 220 Senegal. ; Laboratoire de Fievres Hemorragiques de Guinee, Conakry BP 5680, Guinea. ; Sandia National Laboratories, PO Box 5800 MS1363, Albuquerque, New Mexico 87185-1363, USA. ; Ratoma Ebola Diagnostic Center, Conakry, Guinea. ; MRIGlobal, Kansas City, Missouri 64110-2241, USA. ; Expertise France, Laboratoire K-plan de Forecariah en Guinee, 75006 Paris, France. ; Federation des Laboratoires - HIA Begin, 94163 Saint-Mande cedex, France. ; Laboratoire de Biologie - Centre de Traitement des Soignants, Conakry, Guinea. ; World Health Organization, Conakry BP 817, Guinea. ; London School of Hygiene and Tropical Medicine, London EC1E 7HT, UK. ; Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway. ; Public Health Wales, Cardiff CF11 9LJ, UK. ; Defence Science and Technology Laboratory (Dstl) Porton Down, Salisbury SP4 0JQ, UK. ; Oxford Nanopore Technologies, Oxford OX4 4GA, UK. ; Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. ; Academic Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham B15 2TH, UK. ; Centre of Defence Pathology, Royal Centre for Defence Medicine, Birmingham B15 2TH, UK. ; Queen Elizabeth Hospital, Birmingham B12 2TH, UK. ; Bundeswehr Institute of Microbiology, D-80937 Munich, Germany. ; Institut National de Sante Publique, Conakry BP 1147, Guinea. ; Fogarty International Center, National Institutes of Health, Bethesda, MD 20892-2220, USA. ; Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh EH9 2FL, UK. ; University of Southampton, South General Hospital, Southampton SO16 6YD, UK. ; NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, PHE Porton Down, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26840485" target="_blank"〉PubMed〈/a〉

Description: The Bronze Age of Eurasia (around 3000-1000 BC) was a period of major cultural changes. However, there is debate about whether these changes resulted from the circulation of ideas or from human migrations, potentially also facilitating the spread of languages and certain phenotypic traits. We investigated this by using new, improved methods to sequence low-coverage genomes from 101 ancient humans from across Eurasia. We show that the Bronze Age was a highly dynamic period involving large-scale population migrations and replacements, responsible for shaping major parts of present-day demographic structure in both Europe and Asia. Our findings are consistent with the hypothesized spread of Indo-European languages during the Early Bronze Age. We also demonstrate that light skin pigmentation in Europeans was already present at high frequency in the Bronze Age, but not lactose tolerance, indicating a more recent onset of positive selection on lactose tolerance than previously thought.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Allentoft, Morten E -- Sikora, Martin -- Sjogren, Karl-Goran -- Rasmussen, Simon -- Rasmussen, Morten -- Stenderup, Jesper -- Damgaard, Peter B -- Schroeder, Hannes -- Ahlstrom, Torbjorn -- Vinner, Lasse -- Malaspinas, Anna-Sapfo -- Margaryan, Ashot -- Higham, Tom -- Chivall, David -- Lynnerup, Niels -- Harvig, Lise -- Baron, Justyna -- Della Casa, Philippe -- Dabrowski, Pawel -- Duffy, Paul R -- Ebel, Alexander V -- Epimakhov, Andrey -- Frei, Karin -- Furmanek, Miroslaw -- Gralak, Tomasz -- Gromov, Andrey -- Gronkiewicz, Stanislaw -- Grupe, Gisela -- Hajdu, Tamas -- Jarysz, Radoslaw -- Khartanovich, Valeri -- Khokhlov, Alexandr -- Kiss, Viktoria -- Kolar, Jan -- Kriiska, Aivar -- Lasak, Irena -- Longhi, Cristina -- McGlynn, George -- Merkevicius, Algimantas -- Merkyte, Inga -- Metspalu, Mait -- Mkrtchyan, Ruzan -- Moiseyev, Vyacheslav -- Paja, Laszlo -- Palfi, Gyorgy -- Pokutta, Dalia -- Pospieszny, Lukasz -- Price, T Douglas -- Saag, Lehti -- Sablin, Mikhail -- Shishlina, Natalia -- Smrcka, Vaclav -- Soenov, Vasilii I -- Szeverenyi, Vajk -- Toth, Gusztav -- Trifanova, Synaru V -- Varul, Liivi -- Vicze, Magdolna -- Yepiskoposyan, Levon -- Zhitenev, Vladislav -- Orlando, Ludovic -- Sicheritz-Ponten, Thomas -- Brunak, Soren -- Nielsen, Rasmus -- Kristiansen, Kristian -- Willerslev, Eske -- England -- Nature. 2015 Jun 11;522(7555):167-72. doi: 10.1038/nature14507.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen K, Denmark. ; Department of Historical Studies, University of Gothenburg, 405 30 Gothenburg, Sweden. ; Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, 2800 Kgs Lyngby, Denmark. ; 1] Centre for GeoGenetics, Natural History Museum, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen K, Denmark [2] Faculty of Archaeology, Leiden University, 2300 Leiden, The Netherlands. ; Department of Archaeology and Ancient History, Lund University, 221 00 Lund, Sweden. ; Oxford Radiocarbon Accelerator Unit, University of Oxford, Oxford OX1 3QY, UK. ; Unit of Forensic Anthropology, Department of Forensic Medicine, University of Copenhagen, 2100 Copenhagen, Denmark. ; Institute of Archaeology, University of Wroclaw, 50-139 Wroclaw, Poland. ; Archaeological Institute, University of Zurich, CH-8006, Zurich, Switzerland. ; Department of Anatomy, Wroclaw Medical University, 50-368 Wroclaw, Poland. ; Department of Anthropology, University of Toronto, Toronto ONM5S 2S2, Canada. ; Department of Archeology and General History, Gorno-Altaisk State University, 649000 Gorno-Altaisk, Russia. ; Institute of History and Archaeology RAS (South Ural Department), South Ural State University, 454080 Chelyabinsk, Russia. ; Environmental Research and Material Science and Centre for Textile Research, The National Museum of Denmark, 1471 Copenhagen K, Denmark. ; Peter the Great Museum of Anthropology and Ethnography (Kunstkamera) RAS, 199034 St Petersburg, Russia. ; Department of Anthropology, Polish Academy of Sciences, 50-449 Wroclaw, Poland. ; Biocentre of the Ludwig-Maximilian-University Munchen, 82152 Munich, Germany. ; 1] Department of Biological Anthropology, Institute of Biology, Eotvos Lorand University, H-1117 Budapest, Hungary [2] Department of Anthropology, Hungarian Natural History Museum, H-1083 Budapest, Hungary. ; The Archaeological Museum of Wroclaw, 50-077 Wroclaw, Poland. ; Samara State Academy of Social Science and Humanities, 443099 Samara, Russia. ; Institute of Archaeology of the Hungarian Academy of Sciences, Research Center for the Humanities, H-1250 Budapest, Hungary. ; 1] Institute of Archaeology and Museology, Faculty of Arts, Masaryk University, CZ-602 00 Brno, Czech Republic [2] Department of Vegetation Ecology, Institute of Botany of the Czech Academy of Sciences, CZ-602 00 Brno, Czech Republic. ; Department of Archaeology, University of Tartu, 51003 Tartu, Estonia. ; Archaeological Superintendence of Lombardy, 20123 Milano, Italy. ; Department of Archaeology, University of Vilnius, LT-01513 Vilnius, Lithuania. ; The SAXO Institute, University of Copenhagen, 2300 Copenhagen S, Denmark. ; Department of Evolutionary Biology, Estonian Biocentre and University of Tartu, 51010 Tartu, Estonia. ; Department of History, Yerevan State University, 0025 Yerevan, Armenia. ; 1] Hungarian National Museum, H-1083 Budapest, Hungary [2] Department of Biological Anthropology, University of Szeged, H-6726 Szeged, Hungary. ; Department of Biological Anthropology, University of Szeged, H-6726 Szeged, Hungary. ; Institute of Archaeology and Ethnology of the Polish Academy of Sciences, 61-612 Poznan, Poland. ; Laboratory for Archaeological Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. ; Zoological Institute of the Russian Academy of Sciences, 199034 St Petersburg, Russia. ; Department of Archaeology, State Historical Museum, 109012 Moscow, Russia. ; Institute for History of Medicine and Foreign Languages of the First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic. ; Research Center for the History and Culture of the Turkic Peoples, Gorno-Altaisk State University, 649000 Gorno-Altaisk, Russia. ; Department of Pre- and Early History, Institute of Archaeological Sciences, Faculty of Humanities, Eotvos Lorand University, H-1088 Budapest, Hungary. ; Matrica Museum, 2440 Szazhalombatta, Hungary. ; Laboratory of Ethnogenomics, Institute of Molecular Biology, National Academy of Sciences, 0014 Yerevan, Armenia. ; Department of Archaeology, Faculty of History, Moscow State University, 119991 Moscow, Russia. ; 1] Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, 2800 Kgs Lyngby, Denmark [2] Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen, Denmark. ; Center for Theoretical Evolutionary Genetics, University of California, Berkeley, California 94720-3140, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26062507" target="_blank"〉PubMed〈/a〉

Description: Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history. To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution. Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila. Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes. This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4380271/" 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/PMC4380271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neafsey, Daniel E -- Waterhouse, Robert M -- Abai, Mohammad R -- Aganezov, Sergey S -- Alekseyev, Max A -- Allen, James E -- Amon, James -- Arca, Bruno -- Arensburger, Peter -- Artemov, Gleb -- Assour, Lauren A -- Basseri, Hamidreza -- Berlin, Aaron -- Birren, Bruce W -- Blandin, Stephanie A -- Brockman, Andrew I -- Burkot, Thomas R -- Burt, Austin -- Chan, Clara S -- Chauve, Cedric -- Chiu, Joanna C -- Christensen, Mikkel -- Costantini, Carlo -- Davidson, Victoria L M -- Deligianni, Elena -- Dottorini, Tania -- Dritsou, Vicky -- Gabriel, Stacey B -- Guelbeogo, Wamdaogo M -- Hall, Andrew B -- Han, Mira V -- Hlaing, Thaung -- Hughes, Daniel S T -- Jenkins, Adam M -- Jiang, Xiaofang -- Jungreis, Irwin -- Kakani, Evdoxia G -- Kamali, Maryam -- Kemppainen, Petri -- Kennedy, Ryan C -- Kirmitzoglou, Ioannis K -- Koekemoer, Lizette L -- Laban, Njoroge -- Langridge, Nicholas -- Lawniczak, Mara K N -- Lirakis, Manolis -- Lobo, Neil F -- Lowy, Ernesto -- MacCallum, Robert M -- Mao, Chunhong -- Maslen, Gareth -- Mbogo, Charles -- McCarthy, Jenny -- Michel, Kristin -- Mitchell, Sara N -- Moore, Wendy -- Murphy, Katherine A -- Naumenko, Anastasia N -- Nolan, Tony -- Novoa, Eva M -- O'Loughlin, Samantha -- Oringanje, Chioma -- Oshaghi, Mohammad A -- Pakpour, Nazzy -- Papathanos, Philippos A -- Peery, Ashley N -- Povelones, Michael -- Prakash, Anil -- Price, David P -- Rajaraman, Ashok -- Reimer, Lisa J -- Rinker, David C -- Rokas, Antonis -- Russell, Tanya L -- Sagnon, N'Fale -- Sharakhova, Maria V -- Shea, Terrance -- Simao, Felipe A -- Simard, Frederic -- Slotman, Michel A -- Somboon, Pradya -- Stegniy, Vladimir -- Struchiner, Claudio J -- Thomas, Gregg W C -- Tojo, Marta -- Topalis, Pantelis -- Tubio, Jose M C -- Unger, Maria F -- Vontas, John -- Walton, Catherine -- Wilding, Craig S -- Willis, Judith H -- Wu, Yi-Chieh -- Yan, Guiyun -- Zdobnov, Evgeny M -- Zhou, Xiaofan -- Catteruccia, Flaminia -- Christophides, George K -- Collins, Frank H -- Cornman, Robert S -- Crisanti, Andrea -- Donnelly, Martin J -- Emrich, Scott J -- Fontaine, Michael C -- Gelbart, William -- Hahn, Matthew W -- Hansen, Immo A -- Howell, Paul I -- Kafatos, Fotis C -- Kellis, Manolis -- Lawson, Daniel -- Louis, Christos -- Luckhart, Shirley -- Muskavitch, Marc A T -- Ribeiro, Jose M -- Riehle, Michael A -- Sharakhov, Igor V -- Tu, Zhijian -- Zwiebel, Laurence J -- Besansky, Nora J -- 092654/Wellcome Trust/United Kingdom -- R01 AI050243/AI/NIAID NIH HHS/ -- R01 AI063508/AI/NIAID NIH HHS/ -- R01 AI073745/AI/NIAID NIH HHS/ -- R01 AI076584/AI/NIAID NIH HHS/ -- R01 AI080799/AI/NIAID NIH HHS/ -- R01 AI104956/AI/NIAID NIH HHS/ -- R21 AI101459/AI/NIAID NIH HHS/ -- R56 AI107263/AI/NIAID NIH HHS/ -- SC1 AI109055/AI/NIAID NIH HHS/ -- U19 AI089686/AI/NIAID NIH HHS/ -- U19 AI110818/AI/NIAID NIH HHS/ -- U41 HG007234/HG/NHGRI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):1258522. doi: 10.1126/science.1258522. Epub 2014 Nov 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. neafsey@broadinstitute.org nbesansk@nd.edu. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Medical Entomology and Vector Control, School of Public Health and Institute of Health Researches, Tehran University of Medical Sciences, Tehran, Iran. ; George Washington University, Department of Mathematics and Computational Biology Institute, 45085 University Drive, Ashburn, VA 20147, USA. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. ; National Vector Borne Disease Control Programme, Ministry of Health, Tafea Province, Vanuatu. ; Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy. ; Department of Biological Sciences, California State Polytechnic-Pomona, 3801 West Temple Avenue, Pomona, CA 91768, USA. ; Tomsk State University, 36 Lenina Avenue, Tomsk, Russia. ; Department of Computer Science and Engineering, Eck Institute for Global Health, 211B Cushing Hall, University of Notre Dame, Notre Dame, IN 46556, USA. ; Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Inserm, U963, F-67084 Strasbourg, France. CNRS, UPR9022, IBMC, F-67084 Strasbourg, France. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. ; Faculty of Medicine, Health and Molecular Science, Australian Institute of Tropical Health Medicine, James Cook University, Cairns 4870, Australia. ; Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot SL5 7PY, UK. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. ; Department of Mathematics, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. ; Department of Entomology and Nematology, One Shields Avenue, University of California-Davis, Davis, CA 95616, USA. ; Institut de Recherche pour le Developpement, Unites Mixtes de Recherche Maladies Infectieuses et Vecteurs Ecologie, Genetique, Evolution et Controle, 911, Avenue Agropolis, BP 64501 Montpellier, France. ; Division of Biology, Kansas State University, 271 Chalmers Hall, Manhattan, KS 66506, USA. ; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. ; Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Genomics Platform, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. ; Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou 01 BP 2208, Burkina Faso. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; School of Life Sciences, University of Nevada, Las Vegas, NV 89154, USA. ; Department of Medical Research, No. 5 Ziwaka Road, Dagon Township, Yangon 11191, Myanmar. ; European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK. Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. ; Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Universita degli Studi di Perugia, Perugia, Italy. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Computational Evolutionary Biology Group, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK. ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Bioinformatics Research Laboratory, Department of Biological Sciences, New Campus, University of Cyprus, CY 1678 Nicosia, Cyprus. ; Wits Research Institute for Malaria, Faculty of Health Sciences, and Vector Control Reference Unit, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, Johannesburg, South Africa. ; National Museums of Kenya, P.O. Box 40658-00100, Nairobi, Kenya. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. ; Virginia Bioinformatics Institute, 1015 Life Science Circle, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Medicine Research - Coast, P.O. Box 230-80108, Kilifi, Kenya. ; Harvard School of Public Health, Department of Immunology and Infectious Diseases, Boston, MA 02115, USA. ; Department of Entomology, 1140 East South Campus Drive, Forbes 410, University of Arizona, Tucson, AZ 85721, USA. ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, One Shields Avenue, Davis, CA 95616, USA. ; Department of Life Sciences, Imperial College London, South Kensington Campus, London SW7 2AZ, UK. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, PA 19104, USA. ; Regional Medical Research Centre NE, Indian Council of Medical Research, P.O. Box 105, Dibrugarh-786 001, Assam, India. ; Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. Molecular Biology Program, New Mexico State University, Las Cruces, NM 88003, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. ; Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37235, USA. Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Genetic Medicine and Development, University of Geneva Medical School, Rue Michel-Servet 1, 1211 Geneva, Switzerland. Swiss Institute of Bioinformatics, Rue Michel-Servet 1, 1211 Geneva, Switzerland. ; Department of Entomology, Texas A&M University, College Station, TX 77807, USA. ; Department of Parasitology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. ; Fundacao Oswaldo Cruz, Avenida Brasil 4365, RJ Brazil. Instituto de Medicina Social, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. ; School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Department of Physiology, School of Medicine, Center for Research in Molecular Medicine and Chronic Diseases, Instituto de Investigaciones Sanitarias, University of Santiago de Compostela, Santiago de Compostela, A Coruna, Spain. ; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, CB10 1SA, UK. ; School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool L3 3AF, UK. ; Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA. ; Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, MA 02139, USA. The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, MA 02142, USA. Department of Computer Science, Harvey Mudd College, Claremont, CA 91711, USA. ; Program in Public Health, College of Health Sciences, University of California, Irvine, Hewitt Hall, Irvine, CA 92697, USA. ; Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA. ; Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Malaria Programme, Wellcome Trust Sanger Institute, Cambridge CB10 1SJ, UK. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. Centre of Evolutionary and Ecological Studies (Marine Evolution and Conservation group), University of Groningen, Nijenborgh 7, NL-9747 AG Groningen, Netherlands. ; Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. ; Department of Biology, Indiana University, Bloomington, IN 47405, USA. School of Informatics and Computing, Indiana University, Bloomington, IN 47405, USA. ; Centers for Disease Control and Prevention, 1600 Clifton Road NE MSG49, Atlanta, GA 30329, USA. ; Department of Biology, University of Crete, 700 13 Heraklion, Greece. Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Hellas, Nikolaou Plastira 100 GR-70013, Heraklion, Crete, Greece. Centre of Functional Genomics, University of Perugia, Perugia, Italy. ; Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA. Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. ; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, 12735 Twinbrook Parkway, Rockville, MD 20852, USA. ; Department of Entomology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Program of Genetics, Bioinformatics, and Computational Biology, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. ; Departments of Biological Sciences and Pharmacology, Institutes for Chemical Biology, Genetics and Global Health, Vanderbilt University and Medical Center, Nashville, TN 37235, USA. ; Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, 317 Galvin Life Sciences Building, Notre Dame, IN 46556, USA. neafsey@broadinstitute.org nbesansk@nd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554792" target="_blank"〉PubMed〈/a〉

Description: The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530010/" 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/PMC4530010/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roadmap Epigenomics Consortium -- Kundaje, Anshul -- Meuleman, Wouter -- Ernst, Jason -- Bilenky, Misha -- Yen, Angela -- Heravi-Moussavi, Alireza -- Kheradpour, Pouya -- Zhang, Zhizhuo -- Wang, Jianrong -- Ziller, Michael J -- Amin, Viren -- Whitaker, John W -- Schultz, Matthew D -- Ward, Lucas D -- Sarkar, Abhishek -- Quon, Gerald -- Sandstrom, Richard S -- Eaton, Matthew L -- Wu, Yi-Chieh -- Pfenning, Andreas R -- Wang, Xinchen -- Claussnitzer, Melina -- Liu, Yaping -- Coarfa, Cristian -- Harris, R Alan -- Shoresh, Noam -- Epstein, Charles B -- Gjoneska, Elizabeta -- Leung, Danny -- Xie, Wei -- Hawkins, R David -- Lister, Ryan -- Hong, Chibo -- Gascard, Philippe -- Mungall, Andrew J -- Moore, Richard -- Chuah, Eric -- Tam, Angela -- Canfield, Theresa K -- Hansen, R Scott -- Kaul, Rajinder -- Sabo, Peter J -- Bansal, Mukul S -- Carles, Annaick -- Dixon, Jesse R -- Farh, Kai-How -- Feizi, Soheil -- Karlic, Rosa -- Kim, Ah-Ram -- Kulkarni, Ashwinikumar -- Li, Daofeng -- Lowdon, Rebecca -- Elliott, GiNell -- Mercer, Tim R -- Neph, Shane J -- Onuchic, Vitor -- Polak, Paz -- Rajagopal, Nisha -- Ray, Pradipta -- Sallari, Richard C -- Siebenthall, Kyle T -- Sinnott-Armstrong, Nicholas A -- Stevens, Michael -- Thurman, Robert E -- Wu, Jie -- Zhang, Bo -- Zhou, Xin -- Beaudet, Arthur E -- Boyer, Laurie A -- De Jager, Philip L -- Farnham, Peggy J -- Fisher, Susan J -- Haussler, David -- Jones, Steven J M -- Li, Wei -- Marra, Marco A -- McManus, Michael T -- Sunyaev, Shamil -- Thomson, James A -- Tlsty, Thea D -- Tsai, Li-Huei -- Wang, Wei -- Waterland, Robert A -- Zhang, Michael Q -- Chadwick, Lisa H -- Bernstein, Bradley E -- Costello, Joseph F -- Ecker, Joseph R -- Hirst, Martin -- Meissner, Alexander -- Milosavljevic, Aleksandar -- Ren, Bing -- Stamatoyannopoulos, John A -- Wang, Ting -- Kellis, Manolis -- 5R24HD000836/HD/NICHD NIH HHS/ -- ES017166/ES/NIEHS NIH HHS/ -- F32 HL110473/HL/NHLBI NIH HHS/ -- F32HL110473/HL/NHLBI NIH HHS/ -- K99 HL119617/HL/NHLBI NIH HHS/ -- K99HL119617/HL/NHLBI NIH HHS/ -- P01 DA008227/DA/NIDA NIH HHS/ -- P30AG10161/AG/NIA NIH HHS/ -- P50 MH096890/MH/NIMH NIH HHS/ -- R01 AG015819/AG/NIA NIH HHS/ -- R01 AG017917/AG/NIA NIH HHS/ -- R01 ES024984/ES/NIEHS NIH HHS/ -- R01 ES024992/ES/NIEHS NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- R01 HG007175/HG/NHGRI NIH HHS/ -- R01 HG007354/HG/NHGRI NIH HHS/ -- R01AG15819/AG/NIA NIH HHS/ -- R01AG17917/AG/NIA NIH HHS/ -- R01HG004037/HG/NHGRI NIH HHS/ -- R01HG004037-S1/HG/NHGRI NIH HHS/ -- R01NS078839/NS/NINDS NIH HHS/ -- RC1HG005334/HG/NHGRI NIH HHS/ -- RF1 AG015819/AG/NIA NIH HHS/ -- T32 ES007032/ES/NIEHS NIH HHS/ -- T32 GM007198/GM/NIGMS NIH HHS/ -- T32 GM007266/GM/NIGMS NIH HHS/ -- T32 GM081739/GM/NIGMS NIH HHS/ -- U01 ES017154/ES/NIEHS NIH HHS/ -- U01AG46152/AG/NIA NIH HHS/ -- U01DA025956/DA/NIDA NIH HHS/ -- U01ES017154/ES/NIEHS NIH HHS/ -- U01ES017155/ES/NIEHS NIH HHS/ -- U01ES017156/ES/NIEHS NIH HHS/ -- U01ES017166/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Feb 19;518(7539):317-30. doi: 10.1038/nature14248.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Genetics, Department of Computer Science, 300 Pasteur Dr., Lane Building, L301, Stanford, California 94305-5120, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Biological Chemistry, University of California, Los Angeles, 615 Charles E Young Dr South, Los Angeles, California 90095, USA. ; Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Department of Stem Cell and Regenerative Biology, 7 Divinity Ave, Cambridge, Massachusetts 02138, USA. ; Epigenome Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Genomic Analysis Laboratory, Howard Hughes Medical Institute &The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA. ; Department of Genome Sciences, University of Washington, 3720 15th Ave. NE, Seattle, Washington 98195, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Biology Department, Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA. ; The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 43 Vassar St, Cambridge, Massachusetts 02139, USA. ; 1] Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, Moores Cancer Center, Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. [2] Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093, USA. ; Department of Neurosurgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, California 94158, USA. ; Department of Pathology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0511, USA. ; Department of Medicine, Division of Medical Genetics, University of Washington, 2211 Elliot Avenue, Seattle, Washington 98121, USA. ; 1] Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, 32 Vassar St, Cambridge, Massachusetts 02139, USA. [2] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [3] Department of Computer Science &Engineering, University of Connecticut, 371 Fairfield Way, Storrs, Connecticut 06269, USA. ; Department of Microbiology and Immunology and Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada. ; Bioinformatics Group, Department of Molecular Biology, Division of Biology, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia. ; Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA. ; Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA. ; Institute for Molecular Bioscience, University of Queensland, St Lucia, Queensland 4072, Australia. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. ; 1] Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University in St Louis, 4444 Forest Park Ave, St Louis, Missouri 63108, USA. [2] Department of Computer Science and Engineeering, Washington University in St. Louis, St. Louis, Missouri 63130, USA. ; 1] Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794-3600, USA. [2] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. ; Molecular and Human Genetics Department, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; Biology Department, Massachusetts Institute of Technology, 31 Ames St, Cambridge, Massachusetts 02142, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Brigham &Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA. [3] Harvard Medical School, 25 Shattuck St, Boston, Massachusetts 02115, USA. ; Department of Biochemistry, Keck School of Medicine, University of Southern California, 1450 Biggy Street, Los Angeles, California 90089-9601, USA. ; ObGyn, Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, California 94143, USA. ; Center for Biomolecular Sciences and Engineering, University of Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada. [3] Department of Medical Genetics, University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4. ; Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Medical Genetics, University of British Columbia, 2329 West Mall, Vancouver, BC, Canada, V6T 1Z4. ; Department of Microbiology and Immunology, Diabetes Center, University of California, San Francisco, 513 Parnassus Ave, San Francisco, California 94143-0534, USA. ; 1] University of Wisconsin, Madison, Wisconsin 53715, USA. [2] Morgridge Institute for Research, 330 N. Orchard Street, Madison, Wisconsin 53707, USA. ; USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, 1100 Bates Street, Houston, Texas 77030, USA. ; 1] Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas, Dallas, NSERL, RL10, 800 W Campbell Road, Richardson, Texas 75080, USA. [2] Bioinformatics Division, Center for Synthetic and Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China. ; National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park, North Carolina 27709, USA. ; 1] The Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, Massachusetts 02142, USA. [2] Massachusetts General Hospital, 55 Fruit St, Boston, Massachusetts 02114, USA. [3] Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815-6789, USA. ; 1] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada. [2] Department of Microbiology and Immunology and Centre for High-Throughput Biology, University of British Columbia, 2125 East Mall, Vancouver, British Columbia V6T 1Z4, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25693563" target="_blank"〉PubMed〈/a〉

Description: Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437632/" 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/PMC4437632/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cirulli, Elizabeth T -- Lasseigne, Brittany N -- Petrovski, Slave -- Sapp, Peter C -- Dion, Patrick A -- Leblond, Claire S -- Couthouis, Julien -- Lu, Yi-Fan -- Wang, Quanli -- Krueger, Brian J -- Ren, Zhong -- Keebler, Jonathan -- Han, Yujun -- Levy, Shawn E -- Boone, Braden E -- Wimbish, Jack R -- Waite, Lindsay L -- Jones, Angela L -- Carulli, John P -- Day-Williams, Aaron G -- Staropoli, John F -- Xin, Winnie W -- Chesi, Alessandra -- Raphael, Alya R -- McKenna-Yasek, Diane -- Cady, Janet -- Vianney de Jong, J M B -- Kenna, Kevin P -- Smith, Bradley N -- Topp, Simon -- Miller, Jack -- Gkazi, Athina -- FALS Sequencing Consortium -- Al-Chalabi, Ammar -- van den Berg, Leonard H -- Veldink, Jan -- Silani, Vincenzo -- Ticozzi, Nicola -- Shaw, Christopher E -- Baloh, Robert H -- Appel, Stanley -- Simpson, Ericka -- Lagier-Tourenne, Clotilde -- Pulst, Stefan M -- Gibson, Summer -- Trojanowski, John Q -- Elman, Lauren -- McCluskey, Leo -- Grossman, Murray -- Shneider, Neil A -- Chung, Wendy K -- Ravits, John M -- Glass, Jonathan D -- Sims, Katherine B -- Van Deerlin, Vivianna M -- Maniatis, Tom -- Hayes, Sebastian D -- Ordureau, Alban -- Swarup, Sharan -- Landers, John -- Baas, Frank -- Allen, Andrew S -- Bedlack, Richard S -- Harper, J Wade -- Gitler, Aaron D -- Rouleau, Guy A -- Brown, Robert -- Harms, Matthew B -- Cooper, Gregory M -- Harris, Tim -- Myers, Richard M -- Goldstein, David B -- 089701/Wellcome Trust/United Kingdom -- K08 NS075094/NS/NINDS NIH HHS/ -- P01 AG017586/AG/NIA NIH HHS/ -- P01 AG032953/AG/NIA NIH HHS/ -- P50 AG025688/AG/NIA NIH HHS/ -- R37 NS033123/NS/NINDS NIH HHS/ -- R37 NS083524/NS/NINDS NIH HHS/ -- T32 GM007754/GM/NIGMS NIH HHS/ -- TL1 TR001066/TR/NCATS NIH HHS/ -- UL1 TR001067/TR/NCATS NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1436-41. doi: 10.1126/science.aaa3650. Epub 2015 Feb 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC 27708, USA. ; HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA. ; Institute for Genomic Medicine, Columbia University, New York, NY 10032, USA. ; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA. ; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 2B4, Canada. ; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Duke University School of Medicine, Durham, NC 27708, USA. ; Biogen Idec, Cambridge, MA 02142, USA. ; Neurogenetics DNA Diagnostic Laboratory, Center for Human Genetics Research, Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA. ; Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA. ; Department of Genome Analysis, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, Netherlands. ; Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Republic of Ireland. ; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience, London SE5 8AF, UK. ; Department of Neurology, Brain Center Rudolf Magnus, University Medical Centre Utrecht, 3508 GA Utrecht, Netherlands. ; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan 20149, Italy, and Department of Pathophysiology and Transplantation, Dino Ferrari Center, Universita degli Studi di Milano, Milan 20122, Italy. ; Cedars Sinai Medical Center, Los Angeles, CA 90048, USA. ; Houston Methodist Hospital, Houston, TX 77030, USA, and Weill Cornell Medical College of Cornell University, New York, NY 10065, USA. ; Ludwig Institute for Cancer Research and Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Neurology, Penn ALS Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Neurology, Penn Frontotemporal Degeneration Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Neurology, Center for Motor Neuron Biology and Disease, Columbia University, New York, NY 10032, USA. ; Department of Pediatrics and Medicine, Columbia University, New York, NY 10032, USA. ; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA. ; Department of Neurology, Emory University, Atlanta, GA 30322, USA. ; Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY 10027, USA. ; Biogen Idec, Cambridge, MA 02142, USA. Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. ; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27708, USA. ; Duke ALS Clinic and Durham VA Medical Center, Durham, NC 27708, USA. ; Biogen Idec, Cambridge, MA 02142, USA. tim.harris@biogenidec.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25700176" target="_blank"〉PubMed〈/a〉

Description: Cell growth and proliferation are tightly linked to nutrient availability. The mechanistic target of rapamycin complex 1 (mTORC1) integrates the presence of growth factors, energy levels, glucose and amino acids to modulate metabolic status and cellular responses. mTORC1 is activated at the surface of lysosomes by the RAG GTPases and the Ragulator complex through a not fully understood mechanism monitoring amino acid availability in the lysosomal lumen and involving the vacuolar H(+)-ATPase. Here we describe the uncharacterized human member 9 of the solute carrier family 38 (SLC38A9) as a lysosomal membrane-resident protein competent in amino acid transport. Extensive functional proteomic analysis established SLC38A9 as an integral part of the Ragulator-RAG GTPases machinery. Gain of SLC38A9 function rendered cells resistant to amino acid withdrawal, whereas loss of SLC38A9 expression impaired amino-acid-induced mTORC1 activation. Thus SLC38A9 is a physical and functional component of the amino acid sensing machinery that controls the activation of mTOR.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4376665/" 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/PMC4376665/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rebsamen, Manuele -- Pochini, Lorena -- Stasyk, Taras -- de Araujo, Mariana E G -- Galluccio, Michele -- Kandasamy, Richard K -- Snijder, Berend -- Fauster, Astrid -- Rudashevskaya, Elena L -- Bruckner, Manuela -- Scorzoni, Stefania -- Filipek, Przemyslaw A -- Huber, Kilian V M -- Bigenzahn, Johannes W -- Heinz, Leonhard X -- Kraft, Claudine -- Bennett, Keiryn L -- Indiveri, Cesare -- Huber, Lukas A -- Superti-Furga, Giulio -- P 26682/Austrian Science Fund FWF/Austria -- England -- Nature. 2015 Mar 26;519(7544):477-81. doi: 10.1038/nature14107. Epub 2015 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria. ; Department DiBEST (Biology, Ecology and Earth Sciences), University of Calabria, 87036 Arcavacata di Rende, Italy. ; Biocenter, Division of Cell Biology, Innsbruck Medical University, 6020 Innsbruck, Austria. ; Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25561175" target="_blank"〉PubMed〈/a〉

Description: Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/" 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/PMC4481126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Yongyou -- Desai, Amar -- Yang, Sung Yeun -- Bae, Ki Beom -- Antczak, Monika I -- Fink, Stephen P -- Tiwari, Shruti -- Willis, Joseph E -- Williams, Noelle S -- Dawson, Dawn M -- Wald, David -- Chen, Wei-Dong -- Wang, Zhenghe -- Kasturi, Lakshmi -- Larusch, Gretchen A -- He, Lucy -- Cominelli, Fabio -- Di Martino, Luca -- Djuric, Zora -- Milne, Ginger L -- Chance, Mark -- Sanabria, Juan -- Dealwis, Chris -- Mikkola, Debra -- Naidoo, Jacinth -- Wei, Shuguang -- Tai, Hsin-Hsiung -- Gerson, Stanton L -- Ready, Joseph M -- Posner, Bruce -- Willson, James K V -- Markowitz, Sanford D -- 1P01CA95471-09/CA/NCI NIH HHS/ -- 5P30 CA142543-03/CA/NCI NIH HHS/ -- P01 CA095471/CA/NCI NIH HHS/ -- P30 CA043703/CA/NCI NIH HHS/ -- P30 CA142543/CA/NCI NIH HHS/ -- P30 DK020572/DK/NIDDK NIH HHS/ -- P30 DK097948/DK/NIDDK NIH HHS/ -- P50 CA130810/CA/NCI NIH HHS/ -- P50 CA150964/CA/NCI NIH HHS/ -- R01 CA127590/CA/NCI NIH HHS/ -- R25 CA148052/CA/NCI NIH HHS/ -- R25CA148052/CA/NCI NIH HHS/ -- U54 HL119810/HL/NHLBI NIH HHS/ -- U54HL119810/HL/NHLBI NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):aaa2340. doi: 10.1126/science.aaa2340.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Gastroenterology, Haeundae Paik Hospital, Inje University, Busan 612896, South Korea. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Surgery, Busan Paik Hospital, and Paik Institute of Clinical Research and Ocular Neovascular Research Center, Inje University, Busan, South Korea. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Family Medicine, University of Michigan, Ann Arbor MI 48109, USA. ; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. ; Proteomics Center, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA. ; College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068857" target="_blank"〉PubMed〈/a〉

Description: Severe influenza disease strikes otherwise healthy children and remains unexplained. We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and induced pluripotent stem cell (iPSC)-derived pulmonary epithelial cells produced reduced amounts of type I IFN and displayed increased influenza virus replication. These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. They also show that severe influenza may result from single-gene inborn errors of immunity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431581/" 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/PMC4431581/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ciancanelli, Michael J -- Huang, Sarah X L -- Luthra, Priya -- Garner, Hannah -- Itan, Yuval -- Volpi, Stefano -- Lafaille, Fabien G -- Trouillet, Celine -- Schmolke, Mirco -- Albrecht, Randy A -- Israelsson, Elisabeth -- Lim, Hye Kyung -- Casadio, Melina -- Hermesh, Tamar -- Lorenzo, Lazaro -- Leung, Lawrence W -- Pedergnana, Vincent -- Boisson, Bertrand -- Okada, Satoshi -- Picard, Capucine -- Ringuier, Benedicte -- Troussier, Francoise -- Chaussabel, Damien -- Abel, Laurent -- Pellier, Isabelle -- Notarangelo, Luigi D -- Garcia-Sastre, Adolfo -- Basler, Christopher F -- Geissmann, Frederic -- Zhang, Shen-Ying -- Snoeck, Hans-Willem -- Casanova, Jean-Laurent -- 1U19AI109945/AI/NIAID NIH HHS/ -- 5R01AI100887/AI/NIAID NIH HHS/ -- 5R01NS072381/NS/NINDS NIH HHS/ -- 8UL1TR000043/TR/NCATS NIH HHS/ -- HHSN272201400008C/PHS HHS/ -- R01 AI100887/AI/NIAID NIH HHS/ -- R01 NS072381/NS/NINDS NIH HHS/ -- U19 AI109945/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Apr 24;348(6233):448-53. doi: 10.1126/science.aaa1578. Epub 2015 Mar 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. ; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA. Department of Medicine, Columbia University Medical Center, New York, NY, USA. ; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ; Centre for Molecular and Cellular Biology of Inflammation (CMCBI), King's College London, London SE1 1UL, UK. ; Division of Immunology and Manton Center for Orphan Disease Research, Children's Hospital, Harvard Medical School, Boston, MA, USA. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy. ; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ; Department of Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA. ; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. Study Centre for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France. ; Pediatric Intensive Care Unit, University Hospital, Angers, France. ; General Pediatrics Unit, University Hospital, Angers, France. ; Department of Systems Immunology, Benaroya Research Institute at Virginia Mason, Seattle, WA, USA. Department of Systems Biology, Sidra Medical and Research Center, Doha, Qatar. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. ; Pediatric Immunology, Hematology and Oncology Unit, University Hospital Centre of Angers, Angers, France. INSERM U892, CNRS U6299, Angers, France. ; Division of Immunology and Manton Center for Orphan Disease Research, Children's Hospital, Harvard Medical School, Boston, MA, USA. ; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France. University Paris Descartes, Imagine Institute, Paris, France. Pediatric Immuno-Hematology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France. Howard Hughes Medical Institute, New York, NY, USA. jean-laurent.casanova@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814066" target="_blank"〉PubMed〈/a〉

Description: The four genetically divergent dengue virus (DENV) types are traditionally classified as serotypes. Antigenic and genetic differences among the DENV types influence disease outcome, vaccine-induced protection, epidemic magnitude, and viral evolution. We characterized antigenic diversity in the DENV types by antigenic maps constructed from neutralizing antibody titers obtained from African green monkeys and after human vaccination and natural infections. Genetically, geographically, and temporally, diverse DENV isolates clustered loosely by type, but we found that many are as similar antigenically to a virus of a different type as to some viruses of the same type. Primary infection antisera did not neutralize all viruses of the same DENV type any better than other types did up to 2 years after infection and did not show improved neutralization to homologous type isolates. That the canonical DENV types are not antigenically homogeneous has implications for vaccination and research on the dynamics of immunity, disease, and the evolution of DENV.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Katzelnick, Leah C -- Fonville, Judith M -- Gromowski, Gregory D -- Bustos Arriaga, Jose -- Green, Angela -- James, Sarah L -- Lau, Louis -- Montoya, Magelda -- Wang, Chunling -- VanBlargan, Laura A -- Russell, Colin A -- Thu, Hlaing Myat -- Pierson, Theodore C -- Buchy, Philippe -- Aaskov, John G -- Munoz-Jordan, Jorge L -- Vasilakis, Nikos -- Gibbons, Robert V -- Tesh, Robert B -- Osterhaus, Albert D M E -- Fouchier, Ron A M -- Durbin, Anna -- Simmons, Cameron P -- Holmes, Edward C -- Harris, Eva -- Whitehead, Stephen S -- Smith, Derek J -- 089276/Wellcome Trust/United Kingdom -- DP1-OD000490-01/OD/NIH HHS/ -- HHSN266200700010C/PHS HHS/ -- HHSN272201000040I/HHSN27200004/D04/PHS HHS/ -- HHSN272201400008C/PHS HHS/ -- MR/K021885/1/Medical Research Council/United Kingdom -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1338-43. doi: 10.1126/science.aac5017.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA. ; Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK. Department of Viroscience, Erasmus MC, Rotterdam 3015 GE, Netherlands. ; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ; Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA 94720-3370, USA. ; Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK. ; Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK. ; Department of Medical Research, Ziwaka Road, Yangon, Myanmar. ; Institut Pasteur in Cambodia, Reseau International des Instituts Pasteur, Phnom Penh 12201, Cambodia. ; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane 4001, Australia. Australian Army Malaria Institute, Brisbane 4051, Australia. ; Dengue Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, San Juan 00971, Puerto Rico. ; Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA. Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA. Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA. ; Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand. ; Department of Viroscience, Erasmus MC, Rotterdam 3015 GE, Netherlands. ; Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. ; Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam. Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LJ, UK. Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia. ; Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney 2006, Australia. ; Center for Pathogen Evolution, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. World Health Organization (WHO) Collaborating Center for Modeling, Evolution, and Control of Emerging Infectious Diseases, Cambridge CB2 3EJ, UK. Department of Viroscience, Erasmus MC, Rotterdam 3015 GE, Netherlands. djs200@cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383952" target="_blank"〉PubMed〈/a〉