Search

Your search keyword '"A. Kwiatkowski"' showing total 142 results
Start Over Author "A. Kwiatkowski" Journal nature
142 results on '"A. Kwiatkowski"'

1. Genomic reconstruction of the SARS-CoV-2 epidemic in England

Author

Robson, Samuel C, Connor, Thomas R, Loman, Nicholas J, Golubchik, Tanya, Martinez Nunez, Rocio T, Bonsall, David, Rambaut, Andrew, Snell, Luke B, Ludden, Catherine, Corden, Sally, Nastouli, Eleni, Nebbia, Gaia, Lythgoe, Katrina, Torok, M Estee, Goodfellow, Ian G, Prieto, Jacqui A, Saeed, Kordo, Houlihan, Catherine, Frampton, Dan, Hamilton, William L, Witney, Adam A, Bucca, Giselda, Pope, Cassie F, Moore, Catherine, Thomson, Emma C, Harrison, Ewan M, Smith, Colin P, Rogan, Fiona, Beckwith, Shaun M, Murray, Abigail, Singleton, Dawn, Eastick, Kirstine, Sheridan, Liz A, Randell, Paul, Jackson, Leigh M, Gonçalves, Sónia, Fairley, Derek J, Loose, Matthew W, Watkins, Joanne, Moses, Samuel, Nicholls, Sam, Bull, Matthew, Smith, Darren L, Aanensen, David M, Aggarwal, Dinesh, Shepherd, James G, Curran, Martin D, Parmar, Surendra, Parker, Matthew D, Williams, Catryn, Glaysher, Sharon, Underwood, Anthony P, Bashton, Matthew, Pacchiarini, Nicole, Loveson, Katie F, Byott, Matthew, Carabelli, Alessandro M, Templeton, Kate E, de Silva, Thushan I, Wang, Dennis, Langford, Cordelia F, Gunson, Rory N, Cottrell, Simon, O’Grady, Justin, Kwiatkowski, Dominic, Lillie, Patrick J, Cortes, Nicholas, Moore, Nathan, Thomas, Claire, Burns, Phillipa J, Mahungu, Tabitha W, Liggett, Steven, Beckett, Angela H, Holden, Matthew TG, Levett, Lisa J, Osman, Husam, Hassan-Ibrahim, Mohammed O, Simpson, David A, Chand, Meera, Gupta, Ravi K, Darby, Alistair C, Paterson, Steve, Pybus, Oliver G, Volz, Erik, de Angelis, Daniela, Robertson, David L, Page, Andrew J, Bassett, Andrew R, Wong, Nick, Taha, Yusri, Erkiert, Michelle J, Spencer Chapman, Michael H, Dewar, Rebecca, McHugh, Martin P, Mookerjee, Siddharth, Aplin, Stephen, Harvey, Matthew, Sass, Thea, Umpleby, Helen, and Wheeler, Helen

Subjects
Genetics, Prevention, Emerging Infectious Diseases, Infectious Diseases, Lung, Good Health and Well Being, Amino Acid Substitution, COVID-19, England, Epidemiological Monitoring, Genome, Viral, Genomics, Humans, Molecular Epidemiology, Mutation, Quarantine, SARS-CoV-2, Spatio-Temporal Analysis, Spike Glycoprotein, Coronavirus, Wellcome Sanger Institute COVID-19 Surveillance Team, COVID-19 Genomics UK (COG-UK) Consortium*, General Science & Technology
Abstract

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.

Published
2021

2. TIR1-produced cAMP as a second messenger in transcriptional auxin signalling

Author

Chen, Huihuang, Qi, Linlin, Zou, Minxia, Lu, Mengting, Kwiatkowski, Mateusz, Pei, Yuanrong, Jaworski, Krzysztof, and Friml, Jiří

Abstract

The phytohormone auxin (Aux) is a principal endogenous developmental signal in plants. It mediates transcriptional reprogramming by a well-established canonical signalling mechanism. TIR1/AFB auxin receptors are F-box subunits of an ubiquitin ligase complex; after auxin perception, they associate with Aux/IAA transcriptional repressors and ubiquitinate them for degradation, thus enabling the activation of auxin response factor (ARF) transcription factors1, 2–3. Here we revise this paradigm by showing that without TIR1 adenylate cyclase (AC) activity4, auxin-induced degradation of Aux/IAAs is not sufficient to mediate the transcriptional auxin response. Abolishing the TIR1 AC activity does not affect auxin-induced degradation of Aux/IAAs but renders TIR1 non-functional in mediating transcriptional reprogramming and auxin-regulated development, including shoot, root, root hair growth and lateral root formation. Transgenic plants show that local cAMP production in the vicinity of the Aux/IAA–ARF complex by unrelated AC enzymes bypasses the need for auxin perception and is sufficient to induce ARF-mediated transcription. These discoveries revise the canonical model of auxin signalling and establish TIR1/AFB-produced cAMP as a second messenger essential for transcriptional reprograming.

Published
2025
Full Text
View/download PDF

3. Emergent constraint on Arctic Ocean acidification in the twenty-first century

Author

Terhaar, Jens, Kwiatkowski, Lester, and Bopp, Laurent

Subjects
Influence, Observations, Analysis, Forecasts and trends, Market trend/market analysis, Climate change -- Forecasts and trends -- Analysis -- 21st century AD, Ocean acidification -- Analysis -- Forecasts and trends -- 21st century AD, Density currents -- Observations -- Analysis -- Forecasts and trends -- 21st century AD, Human-environment interactions -- Influence -- Forecasts and trends -- Analysis -- 21st century AD, Human beings -- Influence on nature, Climatic changes -- Forecasts and trends -- Analysis -- 21st century AD
Abstract

Author(s): Jens Terhaar [sup.1] [sup.2] [sup.3] , Lester Kwiatkowski [sup.1] [sup.4] , Laurent Bopp [sup.1] Author Affiliations: (1) LMD/IPSL, Ecole Normale Supérieure/PSL Université, CNRS, Ecole Polytechnique, Sorbonne Université, Paris, France [...], The ongoing uptake of anthropogenic carbon by the ocean leads to ocean acidification, a process that results in a reduction in pH and in the saturation state of biogenic calcium carbonate minerals aragonite ([OMEGA].sub.arag) and calcite ([OMEGA].sub.calc).sup.1,2. Because of its naturally low [OMEGA].sub.arag and [OMEGA].sub.calc (refs. .sup.2,3), the Arctic Ocean is considered the region most susceptible to future acidification and associated ecosystem impacts.sup.4-7. However, the magnitude of projected twenty-first century acidification differs strongly across Earth system models.sup.8. Here we identify an emergent multi-model relationship between the simulated present-day density of Arctic Ocean surface waters, used as a proxy for Arctic deep-water formation, and projections of the anthropogenic carbon inventory and coincident acidification. By applying observations of sea surface density, we constrain the end of twenty-first century Arctic Ocean anthropogenic carbon inventory to 9.0 [plus or minus] 1.6 petagrams of carbon and the basin-averaged [OMEGA].sub.arag and [OMEGA].sub.calc to 0.76 [plus or minus] 0.06 and 1.19 [plus or minus] 0.09, respectively, under the high-emissions Representative Concentration Pathway 8.5 climate scenario. Our results indicate greater regional anthropogenic carbon storage and ocean acidification than previously projected.sup.3,8 and increase the probability that large parts of the mesopelagic Arctic Ocean will be undersaturated with respect to calcite by the end of the century. This increased rate of Arctic Ocean acidification, combined with rapidly changing physical and biogeochemical Arctic conditions.sup.9-11, is likely to exacerbate the impact of climate change on vulnerable Arctic marine ecosystems. Sea surface density observations in the Arctic Ocean reveal a relationship between the present-day surface water density and the anthropogenic carbon inventory and coincident acidification, suggesting that recent acidification projections are underestimates.

Published
2020
Full Text
View/download PDF

4. Comprehensive molecular profiling of lung adenocarcinoma

Author

Collisson, Eric A, Campbell, Joshua D, Brooks, Angela N, Berger, Alice H, Lee, William, Chmielecki, Juliann, Beer, David G, Cope, Leslie, Creighton, Chad J, Danilova, Ludmila, Ding, Li, Getz, Gad, Hammerman, Peter S, Neil Hayes, D, Hernandez, Bryan, Herman, James G, Heymach, John V, Jurisica, Igor, Kucherlapati, Raju, Kwiatkowski, David, Ladanyi, Marc, Robertson, Gordon, Schultz, Nikolaus, Shen, Ronglai, Sinha, Rileen, Sougnez, Carrie, Tsao, Ming-Sound, Travis, William D, Weinstein, John N, Wigle, Dennis A, Wilkerson, Matthew D, Chu, Andy, Cherniack, Andrew D, Hadjipanayis, Angela, Rosenberg, Mara, Weisenberger, Daniel J, Laird, Peter W, Radenbaugh, Amie, Ma, Singer, Stuart, Joshua M, Averett Byers, Lauren, Baylin, Stephen B, Govindan, Ramaswamy, Meyerson, Matthew, Gabriel, Stacey B, Cibulskis, Kristian, Kim, Jaegil, Stewart, Chip, Lichtenstein, Lee, Lander, Eric S, Lawrence, Michael S, Kandoth, Cyriac, Fulton, Robert, Fulton, Lucinda L, McLellan, Michael D, Wilson, Richard K, Ye, Kai, Fronick, Catrina C, Maher, Christopher A, Miller, Christopher A, Wendl, Michael C, Cabanski, Christopher, Mardis, Elaine, Wheeler, David, Balasundaram, Miruna, Butterfield, Yaron SN, Carlsen, Rebecca, Chuah, Eric, Dhalla, Noreen, Guin, Ranabir, Hirst, Carrie, Lee, Darlene, Li, Haiyan I, Mayo, Michael, Moore, Richard A, Mungall, Andrew J, Schein, Jacqueline E, Sipahimalani, Payal, Tam, Angela, Varhol, Richard, Gordon Robertson, A, Wye, Natasja, Thiessen, Nina, Holt, Robert A, Jones, Steven JM, Marra, Marco A, Imielinski, Marcin, Onofrio, Robert C, Hodis, Eran, and Zack, Travis

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Bioinformatics and Computational Biology, Genetics, Clinical Sciences, Oncology and Carcinogenesis, Cancer Genomics, Clinical Research, Rare Diseases, Human Genome, Women's Health, Lung Cancer, Lung, Biotechnology, Cancer, 2.1 Biological and endogenous factors, Adenocarcinoma, Adenocarcinoma of Lung, Cell Cycle Proteins, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genomics, Humans, Lung Neoplasms, Male, Molecular Typing, Mutation, Oncogenes, Sex Factors, Transcriptome, Cancer Genome Atlas Research Network, General Science & Technology
Abstract

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

Published
2014

5. Adenylate cyclase activity of TIR1/AFB auxin receptors in plants

Author

Linlin Qi, Mateusz Kwiatkowski, Huihuang Chen, Lukas Hoermayer, Scott Sinclair, Minxia Zou, Charo I. del Genio, Martin F. Kubeš, Richard Napier, Krzysztof Jaworski, and Jiří Friml

Subjects
Multidisciplinary, Indoleacetic Acids, Arabidopsis Proteins, F-Box Proteins, Arabidopsis, Receptors, Cell Surface, Plant Roots, Second Messenger Systems, Gravitropism, Plant Growth Regulators, Gene Expression Regulation, Plant, Mutation, Cyclic AMP, Adenylyl Cyclases
Abstract

The phytohormone auxin is the major coordinative signal in plant development

Published
2022
Full Text
View/download PDF

6. Malaria protection due to sickle haemoglobin depends on parasite genotype

Author

Band, G, Leffler, EM, Jallow, M, Sisay-Joof, F, Ndila, CM, Macharia, AW, Hubbart, C, Jeffreys, AE, Rowlands, K, Nguyen, T, Gonçalves, S, Ariani, CV, Stalker, J, Pearson, RD, Amato, R, Drury, E, Sirugo, G, d'Alessandro, U, Bojang, KA, Marsh, K, Peshu, N, Saelens, JW, Diakité, M, Taylor, SM, Conway, DJ, Rockett, KA, Kwiatkowski, DP, Williams, TN, and Wellcome Trust

Subjects
EXPRESSION, Male, RESISTANCE LOCI, Genotype, PROTEINS, General Science & Technology, Genes, Protozoan, Hemoglobin, Sickle, Plasmodium falciparum, DIVERSITY, Host Adaptation, Linkage Disequilibrium, MOLECULAR-BASIS, parasitic diseases, Animals, Humans, Parasites, GENOME-WIDE ASSOCIATION, Malaria, Falciparum, Child, Alleles, Science & Technology, Polymorphism, Genetic, Multidisciplinary, PLASMODIUM-FALCIPARUM, Kenya, EXPORT, Multidisciplinary Sciences, Science & Technology - Other Topics, VIRULENCE, Female, Gambia, PLASMEPSIN V
Abstract

Host genetic factors can confer resistance against malaria1, raising the question of whether this has led to evolutionary adaptation of parasite populations. Here we searched for association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children with severe malaria caused by Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and three regions of the parasite genome, which is not explained by population structure or other covariates, and which is replicated in additional samples. The HbS-associated alleles include nonsynonymous variants in the gene for the acyl-CoA synthetase family member2–4PfACS8 on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The alleles are in strong linkage disequilibrium and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparum populations.

Published
2021
Full Text
View/download PDF

7. High-fidelity laser-free universal control of trapped ion qubits

Author

Emanuel Knill, S. C. Burd, Daniel H. Slichter, Scott Glancy, R. T. Sutherland, Andrew C. Wilson, David J. Wineland, H. M. Knaack, Alex Kwiatkowski, David Allcock, R. Srinivas, and Dietrich Leibfried

Subjects
Physics, Quantum Physics, Multidisciplinary, Quantum decoherence, Atomic Physics (physics.atom-ph), FOS: Physical sciences, Laser, Physics - Atomic Physics, Magnetic field, law.invention, law, Quantum mechanics, Qubit, Physics::Atomic Physics, Quantum information, Quantum Physics (quant-ph), Quantum, Microwave, Quantum computer
Abstract

Universal control of multiple qubits—the ability to entangle qubits and to perform arbitrary individual qubit operations1—is a fundamental resource for quantum computing2, simulation3 and networking4. Qubits realized in trapped atomic ions have shown the highest-fidelity two-qubit entangling operations5–7 and single-qubit rotations8 so far. Universal control of trapped ion qubits has been separately demonstrated using tightly focused laser beams9–12 or by moving ions with respect to laser beams13–15, but at lower fidelities. Laser-free entangling methods16–20 may offer improved scalability by harnessing microwave technology developed for wireless communications, but so far their performance has lagged the best reported laser-based approaches. Here we demonstrate high-fidelity laser-free universal control of two trapped-ion qubits by creating both symmetric and antisymmetric maximally entangled states with fidelities of $${1}_{-0.0017}^{+0}$$ and $${0.9977}_{-0.0013}^{+0.0010}$$ , respectively (68 per cent confidence level), corrected for initialization error. We use a scheme based on radiofrequency magnetic field gradients combined with microwave magnetic fields that is robust against multiple sources of decoherence and usable with essentially any trapped ion species. The scheme has the potential to perform simultaneous entangling operations on multiple pairs of ions in a large-scale trapped-ion quantum processor without increasing control signal power or complexity. Combining this technology with low-power laser light delivered via trap-integrated photonics21,22 and trap-integrated photon detectors for qubit readout23,24 provides an opportunity for scalable, high-fidelity, fully chip-integrated trapped-ion quantum computing. Laser-free universal control of two trapped-ion qubits using a combination of radiofrequency and microwave magnetic fields achieves some of the highest fidelities ever reported for two-qubit maximally entangled states.

Published
2021
Full Text
View/download PDF

8. Adenylate cyclase activity of TIR1/AFB auxin receptors in plants

Author

Qi, Linlin, primary, Kwiatkowski, Mateusz, additional, Chen, Huihuang, additional, Hoermayer, Lukas, additional, Sinclair, Scott, additional, Zou, Minxia, additional, del Genio, Charo I., additional, Kubeš, Martin F., additional, Napier, Richard, additional, Jaworski, Krzysztof, additional, and Friml, Jiří, additional

Published
2022
Full Text
View/download PDF

10. Reversal of ocean acidification enhances net coral reef calcification

Author

Albright, Rebecca, Caldeira, Lilian, Hosfelt, Jessica, Kwiatkowski, Lester, Maclaren, Jana K., Mason, Benjamin M., Nebuchina, Yana, Ninokawa, Aaron, Pongratz, Julia, Ricke, Katharine L., Rivlin, Tanya, Schneider, Kenneth, Sesboue, Marine, Shamberger, Kathryn, Silverman, Jacob, Wolfe, Kennedy, Zhu, Kai, and Caldeira, Ken

Subjects
Analysis, Physiological aspects, Research, Calcification (Physiology) -- Analysis, Coral reefs -- Research -- Physiological aspects, Marine ecosystems -- Analysis, Ocean acidification -- Analysis, Coral reefs and islands -- Research -- Physiological aspects, Calcification -- Analysis
Abstract

Approximately one-quarter of the anthropogenic carbon dioxide released into the atmosphere each year is absorbed by the global oceans, causing measurable declines in surface ocean pH, carbonate ion concentration ([C[O.sub.3.sup.2-]), [...]

Published
2016

11. Genetic diversity of the African malaria vector Anopheles gambiae

Author

Miles, Alistair, Harding, Nicholas J., Bottà, Giordano, Clarkson, Chris S., Antão, Tiago, Kozak, Krzysztof, Schrider, Daniel R., Kern, Andrew D., Redmond, Seth, Sharakhov, Igor, Pearson, Richard D., Bergey, Christina, Fontaine, Michael C., Donnelly, Martin J., Lawniczak, Mara K. N., Kwiatkowski, Dominic P., Ayala, Diego, Besansky, Nora J., Burt, Austin, Caputo, Beniamino, della Torre, Alessandra, Godfray, H. Charles J., Hahn, Matthew W., Midega, Janet, Neafsey, Daniel E., O’Loughlin, Samantha, Pinto, João, Riehle, Michelle M., Vernick, Kenneth D., Weetman, David, Wilding, Craig S., White, Bradley J., Troco, Arlete D., Diabaté, Abdoulaye, Costantini, Carlo, Rohatgi, Kyanne R., Elissa, Nohal, Coulibaly, Boubacar, Dinis, João, Mbogo, Charles, Bejon, Philip, Mawejje, Henry D., Stalker, Jim, Rockett, Kirk, Drury, Eleanor, Mead, Daniel, Jeffreys, Anna, Hubbart, Christina, Rowlands, Kate, Isaacs, Alison T., Jyothi, Dushyanth, Malangone, Cinzia, Vauterin, Paul, Jeffery, Ben, Wright, Ian, Hart, Lee, Kluczyński, Krzysztof, Cornelius, Victoria, MacInnis, Bronwyn, Henrichs, Christa, and Giacomantonio, Rachel

Published
2017
Full Text
View/download PDF

12. SARS-CoV-2 evolution during treatment of chronic infection

Author

Kemp, S. A., Collier, D. A., Datir, R. P., Ferreira, I. A. T. M., Gayed, S., Jahun, A., Hosmillo, M., Rees-Spear, C., Mlcochova, P., Lumb, I. U., Roberts, D. J., Chandra, A., Temperton, N., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Gleadall, N., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Estee Torok, M., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Abnizova, I., Aigrain, L., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Betteridge, E., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Bonfield, J., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Goodwin, S., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Liddle, J., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Makunin, A., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mccarthy, S., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Puethe, C., Quail, M., Rajan, D., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Scott, C., Seekings, P., Shirley, L., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Jansen Van, P., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Whitwham, A., Widaa, S., Williams, M., Wilson, M., Wright, S., Farr, B. W., Quail, M. A., Thurston, S. A. J., Bronner, I. F., Redshaw, N. M., Lensing, S. V., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Sharrocks, K., Blane, E., Modis, Y., Leigh, K. E., Briggs, J. A. G., van Gils, M. J., Smith, K. G. C., Bradley, J. R., Doffinger, R., Ceron-Gutierrez, L., Barcenas-Morales, G., Pollock, D. D., Goldstein, R. A., Smielewska, A., Skittrall, J. P., Gouliouris, T., Goodfellow, I. G., Gkrania-Klotsas, E., Illingworth, C. J. R., Mccoy, L. E., Gupta, R. K., Medical Microbiology and Infection Prevention, AII - Infectious diseases, Collier, Dami A [0000-0001-5446-4423], Jahun, Aminu [0000-0002-4585-1701], Temperton, Nigel [0000-0002-7978-3815], Modis, Yorgo [0000-0002-6084-0429], Briggs, John AG [0000-0003-3990-6910], Goldstein, Richard A [0000-0001-5148-4672], Skittrall, Jordan P [0000-0002-8228-3758], Gkrania-Klotsas, Effrossyni [0000-0002-0930-8330], McCoy, Laura E [0000-0001-9503-7946], Gupta, Ravindra K [0000-0001-9751-1808], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, Time Factors, viruses, Passive, Antibodies, Viral, CITIID-NIHR BioResource COVID-19 Collaboration, 2.1 Biological and endogenous factors, Viral, Aetiology, Neutralizing, Lung, Phylogeny, neutralising antibodies, Infectivity, education.field_of_study, Genome, Multidisciplinary, Alanine, biology, High-Throughput Nucleotide Sequencing, Viral Load, Spike Glycoprotein, Virus Shedding, Adenosine Monophosphate, Aged, Antibodies, Neutralizing, COVID-19, Chronic Disease, Genome, Viral, Humans, Immune Evasion, Immune Tolerance, Immunization, Passive, Immunosuppression Therapy, Mutagenesis, Mutant Proteins, Mutation, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Evolution, Molecular, Infectious Diseases, Pneumonia & Influenza, Antibody, Infection, Viral load, Biotechnology, Evolution, General Science & Technology, antibody escape, Convalescent plasma, 030106 microbiology, Population, evasion, Antibodies, Virus, Article, Vaccine Related, resistance, 03 medical and health sciences, Immune system, COVID-19 Genomics UK (COG-UK) Consortium, Biodefense, Genetics, Viral shedding, education, COVID-19 Serotherapy, QR355, Prevention, Wild type, Molecular, Pneumonia, Virology, COVID-19 Drug Treatment, Coronavirus, Emerging Infectious Diseases, Good Health and Well Being, 030104 developmental biology, biology.protein, Immunization, immune suppression, mutation
Abstract

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.

Published
2021

14. Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution

Author

Rutledge, Gavin G., Böhme, Ulrike, Sanders, Mandy, Reid, Adam J., Cotton, James A., Maiga-Ascofare, Oumou, Djimdé, Abdoulaye A., Apinjoh, Tobias O., Amenga-Etego, Lucas, Manske, Magnus, Barnwell, John W., Renaud, François, Ollomo, Benjamin, Prugnolle, Franck, Anstey, Nicholas M., Auburn, Sarah, Price, Ric N., McCarthy, James S., Kwiatkowski, Dominic P., Newbold, Chris I., Berriman, Matthew, and Otto, Thomas D.

Published
2017
Full Text
View/download PDF

15. Coordinated regulation of protein synthesis and degradation by mTORC1

Author

Zhang, Yinan, Nicholatos, Justin, Dreier, John R., Ricoult, Stephane J.H., Widenmaier, Scott B., Hotamisligil, Gokhan S., Kwiatkowski, David J., and Manning, Brendan D.

Subjects
Physiological aspects, Genetic aspects, Cellular signal transduction -- Genetic aspects, Proteolysis -- Genetic aspects, Protein synthesis -- Genetic aspects, Genetic regulation -- Physiological aspects, Protein biosynthesis -- Genetic aspects
Abstract

In response to growth signals, mTORC1 promotes anabolic processes, such as protein synthesis, and its chronic activation is believed to underlie a variety of complex human diseases, including cancer and [...], Eukaryotic cells coordinately control anabolic and catabolic processes to maintain cell and tissue homeostasis. Mechanistic target of rapamycin complex 1 (mTORC1) promotes nutrient-consuming-anabolic processes, such as protein synthesis (1). Here we show that as well as increasing protein synthesis, mTORC1 activation in mouse and human cells also promotes an increased capacity for protein degradation. Cells with activated mTORC1 exhibited elevated levels of intact and active proteasomes through a global increase in the expression of genes encoding proteasome subunits. The increase in proteasome gene expression, cellular proteasome content, and rates of protein turnover downstream of mTORC1 were all dependent on induction of the transcription factor nuclear factor erythroid-derived 2-related factor 1 (NRF1; also known as NFE2L1). Genetic activation of mTORC1 through loss of the tuberous sclerosis complex tumour suppressors, TSC1 or TSC2, or physiological activation of mTORC1 in response to growth factors or feeding resulted in increased NRF1 expression in cells and tissues. We find that this NRF1-dependent elevation in proteasome levels serves to increase the intracellular pool of amino acids, which thereby influences rates of new protein synthesis. Therefore, mTORC1 signalling increases the efficiency of proteasome-mediated protein degradation for both quality control and as a mechanism to supply substrate for sustained protein synthesis.

Published
2014

16. Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

Author

Kwiatkowski, Nicholas, Zhang, Tinghu, Rahl, Peter B., Abraham, Brian J., Reddy, Jessica, Ficarro, Scott B., Dastur, Anahita, Amzallag, Arnaud, Ramaswamy, Sridhar, Tesar, Bethany, Jenkins, Catherine E., Hannett, Nancy M., McMillin, Douglas, Sanda, Takaomi, Sim, Taebo, Kim, Nam Doo, Look, Thomas, Mitsiades, Constantine S., Weng, Andrew P., Brown, Jennifer R., Benes, Cyril H., Marto, Jarrod A., Young, Richard A., and Gray, Nathanael S.

Subjects
Care and treatment, Analysis, Research, Genetic aspects, Health aspects, Pharmacology -- Analysis, Cancer -- Research -- Genetic aspects -- Care and treatment, Transcription (Genetics) -- Analysis, Cysteine -- Analysis -- Health aspects, Transcription factors -- Research, Genetic regulation -- Analysis, Genetic transcription -- Analysis
Abstract

In an effort to discover new inhibitors of kinases that regulate gene transcription, we performed cell-based screening and kinase selectivity profiling of a library of known and novel ATP-site-directed kinase [...], Tumour oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state (1), but direct pharmacological inhibition of transcription factors has so far proven difficult (2). However, the transcriptional machinery contains various enzymatic cofactors that can be targeted for the development of new therapeutic candidates (3), including cyclin-dependent kinases (CDKs) (4). Here we present the discovery and characterization of a covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell-line profiling indicates that a subset of cancer cell lines, including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL cells shows that THZ1 disproportionally affects transcription of RUNX1 and suggests that sensitivity to THZ1 may be due to vulnerability conferred by the RUNX1 super-enhancer and the key role of RUNX1 in the core transcriptional regulatory circuitry of these tumour cells. Pharmacological modulation of CDK7 kinase activity may thus provide an approach to identify and treat tumour types that are dependent on transcription for maintenance of the oncogenic state.

Published
2014

17. Arctic Ocean annual high in [Formula: see text] could shift from winter to summer

Author

James C, Orr, Lester, Kwiatkowski, and Hans-Otto, Pörtner

Subjects
Aquatic Organisms, Hot Temperature, Arctic Regions, Oceans and Seas, Animals, Ice Cover, Seawater, Seasons, Carbon Dioxide, Hydrogen-Ion Concentration
Abstract

Long-term stress on marine organisms from ocean acidification will differ between seasons. As atmospheric carbon dioxide (CO

Published
2021

18. A transcriptional switch underlies commitment to sexual development in malaria parasites

Author

Kafsack, Bjorn F.C., Rovira-Graells, Nuria, Clark, Taane G., Bancells, Cristina, Crowley, Valerie M., Campino, Susana G., Williams, April E., Drought, Laura G., Kwiatkowski, Dominic P., Baker, David A., Cortes, Alfred, and Llinas, Manuel

Subjects
Physiological aspects, Genetic aspects, Gametocytes -- Physiological aspects, Life cycle assessment, Plasmodium falciparum -- Physiological aspects, Malaria -- Genetic aspects
Abstract

From its uptake in a mosquito blood meal to initial infection of red blood cells in the subsequent host, the malaria parasite Plasmodium falciparum goes through at least seven key [...], The life cycles of many parasites involve transitions between disparate host species, requiring these parasites to go through multiple developmental stages adapted to each of these specialized niches. Transmission of malaria parasites (Plasmodium spp.) from humans to the mosquito vector requires differentiation from asexual stages replicating within red blood cells into non-dividing male and female gametocytes. Although gametocytes were first described in 1880, our understanding of the molecular mechanisms involved in commitment to gametocyte formation is extremely limited, and disrupting this critical developmental transition remains a long-standing goal (1). Here we show that expression levels of the DNA-binding protein PfAP2-G correlate strongly with levels of gametocyte formation. Using independent forward and reverse genetics approaches, we demonstrate that PfAP2-G function is essential for parasite sexual differentiation. By combining genome-wide PfAP2-G cognate motif occurrence with global transcriptional changes resulting from PfAP2G ablation, we identify early gametocyte genes as probable targets of PfAP2-G and show that their regulation by PfAP2-G is critical for their wild-type level expression. In the asexual blood-stage parasites pfap2-g appears to be among a set of epigenetically silenced loci (2,3) prone to spontaneous activation (4). Stochastic activation presents a simple mechanism for a low baseline of gametocyte production. Overall, these findings identify PfAP2-G as a master regulator of sexual-stage development in malaria parasites and mark the first discovery of a transcriptional switch controlling a differentiation decision in protozoan parasites.

Published
2014

19. A novel locus of resistance to severe malaria in a region of ancient balancing selection

Author

Band, Gavin, Rockett, Kirk A., Spencer, Chris C.A., Kwiatkowski, Dominic P., Le, Quang Si, Clarke, Geraldine M., Kivinen, Katja, Leffler, Ellen M., Cornelius, Victoria, Conway, David J., Williams, Thomas N., Taylor, Terrie, Bojang, Kalifa A., Doumbo, Ogobara, Thera, Mahamadou A., Modiano, David, Sirima, Sodiomon B., Wilson, Michael D., Koram, Kwadwo A., Agbenyega, Tsiri, Achidi, Eric, Marsh, Kevin, Reyburn, Hugh, Drakeley, Chris, Riley, Eleanor, Molyneux, Malcolm, Jallow, Muminatou, Pinder, Margaret, Toure, Ousmane B., Konate, Salimata, Sissoko, Sibiri, Bougouma, Edith C., Mangano, Valentina D., Amenga-Etego, Lucas N., Ghansah, Anita K., Hodgson, Abraham V.O., Ansong, Daniel, Enimil, Anthony, Evans, Jennifer, Apinjoh, Tobias O., Macharia, Alexander, Ndila, Carolyne M., Newton, Charles, Peshu, Norbert, Uyoga, Sophie, Manjurano, Alphaxard, Kachala, David, Nyirongo, Vysaul, Mead, Daniel, Drury, Eleanor, Auburn, Sarah, Campino, Susana G., MacInnis, Bronwyn, Stalker, Jim, Gray, Emma, Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Mendy, Alieu, Craik, Rachel, Fitzpatrick, Kathryn, Molloy, Sile, Hart, Lee, Hutton, Robert, Kerasidou, Angeliki, and Johnson, Kimberly J.

Published
2015
Full Text
View/download PDF

20. A global reference for human genetic variation

Author

Altshuler, David M., (Co-Chair), Durbin, Richard M., (Co-Chair, Principal Investigator), Donnelly, Peter, Green, Eric D., Nickerson, Deborah A., Boerwinkle, Eric, Doddapaneni, Harsha, Han, Yi, Korchina, Viktoriya, Kovar, Christie, Lee, Sandra, Muzny, Donna, Reid, Jeffrey G., Zhu, Yiming, Wang, Jun, (Principal Investigator), Chang, Yuqi, Feng, Qiang, Fang, Xiaodong, Guo, Xiaosen, Jian, Min, Jiang, Hui, Jin, Xin, Lan, Tianming, Li, Guoqing, Li, Jingxiang, Li, Yingrui, Liu, Shengmao, Liu, Xiao, Lu, Yao, Ma, Xuedi, Tang, Meifang, Wang, Bo, Wang, Guangbiao, Wu, Honglong, Wu, Renhua, Xu, Xun, Yin, Ye, Zhang, Dandan, Zhang, Wenwei, Zhao, Jiao, Zhao, Meiru, Zheng, Xiaole, Lander, Eric S., (Principal Investigator), Gabriel, Stacey B., (Co-Chair), Gupta, Namrata, Gharani, Neda, Toji, Lorraine H., Gerry, Norman P., Resch, Alissa M., Barker, Jonathan, Gil, Laurent, Hunt, Sarah E., Kelman, Gavin, Kulesha, Eugene, Leinonen, Rasko, McLaren, William M., Radhakrishnan, Rajesh, Roa, Asier, Smirnov, Dmitriy, Smith, Richard E., Streeter, Ian, Thormann, Anja, Toneva, Iliana, Vaughan, Brendan, Zheng-Bradley, Xiangqun, Bentley, David R., (Principal Investigator), Grocock, Russell, Humphray, Sean, James, Terena, Kingsbury, Zoya, Lehrach, Hans, (Principal Investigator), Sudbrak, Ralf, (Project Leader), Albrecht, Marcus W., Amstislavskiy, Vyacheslav S., Borodina, Tatiana A., Lienhard, Matthias, Mertes, Florian, Sultan, Marc, Timmermann, Bernd, Yaspo, Marie-Laure, Mardis, Elaine R., (Co-Principal Investigator) (Co-Chair), Wilson, Richard K., (Co-Principal Investigator), Fulton, Lucinda, Fulton, Robert, Ananiev, Victor, Belaia, Zinaida, Beloslyudtsev, Dimitriy, Bouk, Nathan, Chen, Chao, Church, Deanna, Cohen, Robert, Cook, Charles, Garner, John, Hefferon, Timothy, Kimelman, Mikhail, Liu, Chunlei, Lopez, John, Meric, Peter, O’Sullivan, Chris, Ostapchuk, Yuri, Phan, Lon, Ponomarov, Sergiy, Schneider, Valerie, Shekhtman, Eugene, Sirotkin, Karl, Slotta, Douglas, Zhang, Hua, Balasubramaniam, Senduran, Burton, John, Danecek, Petr, Keane, Thomas M., Kolb-Kokocinski, Anja, McCarthy, Shane, Stalker, James, Quail, Michael, Schmidt, Jeanette P., (Principal Investigator), Davies, Christopher J., Gollub, Jeremy, Webster, Teresa, Wong, Brant, Zhan, Yiping, Auton, Adam, (Principal Investigator), Campbell, Christopher L., Kong, Yu, Marcketta, Anthony, Yu, Fuli, (Project Leader), Antunes, Lilian, Bainbridge, Matthew, Sabo, Aniko, Huang, Zhuoyi, Coin, Lachlan J. M., Fang, Lin, Li, Qibin, Li, Zhenyu, Lin, Haoxiang, Liu, Binghang, Luo, Ruibang, Shao, Haojing, Xie, Yinlong, Ye, Chen, Yu, Chang, Zhang, Fan, Zheng, Hancheng, Zhu, Hongmei, Alkan, Can, Dal, Elif, Kahveci, Fatma, Garrison, Erik P., (Project Lead), Kural, Deniz, Lee, Wan-Ping, Leong, Wen Fung, Stromberg, Michael, Ward, Alistair N., Wu, Jiantao, Zhang, Mengyao, Daly, Mark J., (Principal Investigator), DePristo, Mark A., (Project Leader), Handsaker, Robert E., (Project Leader), Banks, Eric, Bhatia, Gaurav, del Angel, Guillermo, Genovese, Giulio, Li, Heng, Kashin, Seva, Nemesh, James C., Poplin, Ryan E., Yoon, Seungtai C., (Principal Investigator), Lihm, Jayon, Makarov, Vladimir, Clark, Andrew G., (Principal Investigator), Gottipati, Srikanth, Keinan, Alon, Rodriguez-Flores, Juan L., Rausch, Tobias, (Project Leader), Fritz, Markus H., Stütz, Adrian M., Beal, Kathryn, Datta, Avik, Herrero, Javier, Ritchie, Graham R. S., Zerbino, Daniel, Sabeti, Pardis C., (Principal Investigator), Shlyakhter, Ilya, Schaffner, Stephen F., Vitti, Joseph, Cooper, David N., (Principal Investigator), Ball, Edward V., Stenson, Peter D., Barnes, Bret, Bauer, Markus, Cheetham, Keira R., Cox, Anthony, Eberle, Michael, Kahn, Scott, Murray, Lisa, Peden, John, Shaw, Richard, Kenny, Eimear E., (Principal Investigator), Batzer, Mark A., (Principal Investigator), Konkel, Miriam K., Walker, Jerilyn A., MacArthur, Daniel G., (Principal Investigator), Lek, Monkol, Herwig, Ralf, Koboldt, Daniel C., Larson, David, Ye, Kai, Gravel, Simon, Swaroop, Anand, Chew, Emily, Lappalainen, Tuuli, (Principal Investigator), Erlich, Yaniv, (Principal Investigator), Gymrek, Melissa, Willems, Thomas Frederick, Simpson, Jared T., Shriver, Mark D., (Principal Investigator), Rosenfeld, Jeffrey A., (Principal Investigator), Montgomery, Stephen B., (Principal Investigator), De La Vega, Francisco M., (Principal Investigator), Byrnes, Jake K., Carroll, Andrew W., DeGorter, Marianne K., Lacroute, Phil, Maples, Brian K., Martin, Alicia R., Moreno-Estrada, Andres, Shringarpure, Suyash S., Zakharia, Fouad, Halperin, Eran, (Principal Investigator), Baran, Yael, Cerveira, Eliza, Hwang, Jaeho, Malhotra, Ankit, (Co-Project Lead), Plewczynski, Dariusz, Radew, Kamen, Romanovitch, Mallory, Zhang, Chengsheng, (Co-Project Lead), Hyland, Fiona C. L., Craig, David W., (Principal Investigator), Christoforides, Alexis, Homer, Nils, Izatt, Tyler, Kurdoglu, Ahmet A., Sinari, Shripad A., Squire, Kevin, Xiao, Chunlin, Sebat, Jonathan, (Principal Investigator), Antaki, Danny, Gujral, Madhusudan, Noor, Amina, Ye, Kenny, Burchard, Esteban G., (Principal Investigator), Hernandez, Ryan D., (Principal Investigator), Gignoux, Christopher R., Haussler, David, (Principal Investigator), Katzman, Sol J., Kent, James W., Howie, Bryan, Ruiz-Linares, Andres, (Principal Investigator), Dermitzakis, Emmanouil T., (Principal Investigator), Devine, Scott E., (Principal Investigator), Abecasis, Gonçalo R., (Principal Investigator) (Co-Chair), Kang, Hyun Min, (Project Leader), Kidd, Jeffrey M., (Principal Investigator), Blackwell, Tom, Caron, Sean, Chen, Wei, Emery, Sarah, Fritsche, Lars, Fuchsberger, Christian, Jun, Goo, Li, Bingshan, Lyons, Robert, Scheller, Chris, Sidore, Carlo, Song, Shiya, Sliwerska, Elzbieta, Taliun, Daniel, Tan, Adrian, Welch, Ryan, Wing, Mary Kate, Zhan, Xiaowei, Awadalla, Philip, (Principal Investigator), Hodgkinson, Alan, Li, Yun, Shi, Xinghua, (Principal Investigator), Quitadamo, Andrew, Lunter, Gerton, (Principal Investigator), McVean, Gil A., (Principal Investigator) (Co-Chair), Marchini, Jonathan L., (Principal Investigator), Myers, Simon, (Principal Investigator), Churchhouse, Claire, Delaneau, Olivier, Gupta-Hinch, Anjali, Kretzschmar, Warren, Iqbal, Zamin, Mathieson, Iain, Menelaou, Androniki, Rimmer, Andy, Xifara, Dionysia K., Oleksyk, Taras K., (Principal Investigator), Fu, Yunxin, (Principal Investigator), Liu, Xiaoming, Xiong, Momiao, Jorde, Lynn, (Principal Investigator), Witherspoon, David, Xing, Jinchuan, Browning, Brian L., (Principal Investigator), Browning, Sharon R., (Principal Investigator), Hormozdiari, Fereydoun, Sudmant, Peter H., Khurana, Ekta, (Principal Investigator), Hurles, Matthew E., (Principal Investigator), Albers, Cornelis A., Ayub, Qasim, Chen, Yuan, Colonna, Vincenza, Jostins, Luke, Walter, Klaudia, Xue, Yali, Abyzov, Alexej, Balasubramanian, Suganthi, Chen, Jieming, Clarke, Declan, Fu, Yao, Harmanci, Arif O., Jin, Mike, Lee, Donghoon, Liu, Jeremy, Mu, Xinmeng Jasmine, Zhang, Jing, Zhang, Yan, McCarroll, Steven A., (Principal Investigator), Hartl, Chris, Shakir, Khalid, Degenhardt, Jeremiah, Korbel, Jan O., (Principal Investigator) (Co-Chair), Meiers, Sascha, Raeder, Benjamin, Casale, Francesco Paolo, Stegle, Oliver, Lameijer, Eric-Wubbo, Ding, Li, (Principal Investigator), Hall, Ira, Lee, Charles, (Principal Investigator) (Co-Chair), Bafna, Vineet, Michaelson, Jacob, Gardner, Eugene J., (Project Leader), Mills, Ryan E., (Principal Investigator), Dayama, Gargi, Chen, Ken, (Principle Investigator), Fan, Xian, Chong, Zechen, Chen, Tenghui, Eichler, Evan E., (Principal Investigator) (Co-Chair), Chaisson, Mark J., Huddleston, John, Malig, Maika, Nelson, Bradley J., Parrish, Nicholas F., Blackburne, Ben, Lindsay, Sarah J., Ning, Zemin, Zhang, Yujun, Lam, Hugo, Sisu, Cristina, Gibbs, Richard A., (Principal Investigator) (Co-Chair), Challis, Danny, Evani, Uday S., Lu, James, Nagaswamy, Uma, Yu, Jin, Li, Wangshen, Marth, Gabor T., (Principal Investigator) (Co-Chair), Habegger, Lukas, Yu, Haiyuan, (Principal Investigator), Cunningham, Fiona, Dunham, Ian, Lage, Kasper, (Principal Investigator), Jespersen, Jakob Berg, Horn, Heiko, Tyler-Smith, Chris, (Principal Investigator) (Co-Chair), Gerstein, Mark B., (Principal Investigator) (Co-Chair), Kim, Donghoon, Desalle, Rob, Narechania, Apurva, Wilson Sayres, Melissa A., Bustamante, Carlos D., (Principal Investigator) (Co-Chair), Mendez, Fernando L., Poznik, David G., Underhill, Peter A., Coin, Lachlan, (Principal Investigator), Mittelman, David, Banerjee, Ruby, Cerezo, Maria, Fitzgerald, Thomas W., Louzada, Sandra, Massaia, Andrea, Ritchie, Graham R., Yang, Fengtang, Kalra, Divya, Hale, Walker, Dan, Xu, Flicek, Paul, (Principal Investigator) (Co-Chair), Clarke, Laura, (Project Lead), Sherry, Stephen T., (Principal Investigator) (Co-Chair), Chakravarti, Aravinda, (Co-Chair), Knoppers, Bartha M., (Co-Chair), Barnes, Kathleen C., Beiswanger, Christine, Cai, Hongyu, Cao, Hongzhi, Henn, Brenna, Jones, Danielle, Kaye, Jane S., Kent, Alastair, Kerasidou, Angeliki, Mathias, Rasika, Ossorio, Pilar N., Parker, Michael, Rotimi, Charles N., Royal, Charmaine D., Sandoval, Karla, Su, Yeyang, Tian, Zhongming, Tishkoff, Sarah, Via, Marc, Wang, Yuhong, Yang, Ling, Zhu, Jiayong, Bodmer, Walter, Bedoya, Gabriel, Cai, Zhiming, Gao, Yang, Chu, Jiayou, Peltonen, Leena, Garcia-Montero, Andres, Orfao, Alberto, Dutil, Julie, Martinez-Cruzado, Juan C., Mathias, Rasika A., Hennis, Anselm, Watson, Harold, McKenzie, Colin, Qadri, Firdausi, LaRocque, Regina, Deng, Xiaoyan, Asogun, Danny, Folarin, Onikepe, Happi, Christian, Omoniwa, Omonwunmi, Stremlau, Matt, Tariyal, Ridhi, Jallow, Muminatou, Joof, Fatoumatta Sisay, Corrah, Tumani, Rockett, Kirk, Kwiatkowski, Dominic, Kooner, Jaspal, Hiê`n, Trâ`n Tinh, Dunstan, Sarah J., Hang, Nguyen Thuy, Fonnie, Richard, Garry, Robert, Kanneh, Lansana, Moses, Lina, Schieffelin, John, Grant, Donald S., Gallo, Carla, Poletti, Giovanni, Saleheen, Danish, Rasheed, Asif, Brooks, Lisa D., Felsenfeld, Adam L., McEwen, Jean E., Vaydylevich, Yekaterina, Duncanson, Audrey, Dunn, Michael, Schloss, Jeffery A., and Yang, Huanming

Published
2015
Full Text
View/download PDF

21. High-fidelity laser-free universal control of trapped ion qubits

Author

R, Srinivas, S C, Burd, H M, Knaack, R T, Sutherland, A, Kwiatkowski, S, Glancy, E, Knill, D J, Wineland, D, Leibfried, A C, Wilson, D T C, Allcock, and D H, Slichter

Abstract

Universal control of multiple qubits-the ability to entangle qubits and to perform arbitrary individual qubit operations

Published
2021

22. Basigin is a receptor essential for erythrocyte invasion by plasmodium Falciparum

Author

Crosnier, Cecile, Bustamante, Leyla Y., Bartholdson, S. Josefin, Bei, Amy K., Theron, Michel, Uchikawa, Makoto, Mboup, Souleymane, Ndir, Omar, Kwiatkowski, Dominic P., Duraisingh, Manoj T., Rayner, Julian C., and Wright, Gavin J.

Subjects
Physiological aspects, Research, Causes of, Plasmodium falciparum -- Physiological aspects -- Research, Malaria -- Causes of -- Research
Abstract

Erythrocyte invasion by Plasmodium falciparum is central to the pathogenesis of malaria. Invasion requires a series of extracellular recognition events between erythrocyte receptors and ligands on the merozoite, the invasive [...]

Published
2011

23. The African Genome Variation Project shapes medical genetics in Africa

Author

Gurdasani, Deepti, Carstensen, Tommy, Tekola-Ayele, Fasil, Pagani, Luca, Tachmazidou, Ioanna, Hatzikotoulas, Konstantinos, Karthikeyan, Savita, Iles, Louise, Pollard, Martin O., Choudhury, Ananyo, Ritchie, Graham R. S., Xue, Yali, Asimit, Jennifer, Nsubuga, Rebecca N., Young, Elizabeth H., Pomilla, Cristina, Kivinen, Katja, Rockett, Kirk, Kamali, Anatoli, Doumatey, Ayo P., Asiki, Gershim, Seeley, Janet, Sisay-Joof, Fatoumatta, Jallow, Muminatou, Tollman, Stephen, Mekonnen, Ephrem, Ekong, Rosemary, Oljira, Tamiru, Bradman, Neil, Bojang, Kalifa, Ramsay, Michele, Adeyemo, Adebowale, Bekele, Endashaw, Motala, Ayesha, Norris, Shane A., Pirie, Fraser, Kaleebu, Pontiano, Kwiatkowski, Dominic, Tyler-Smith, Chris, Rotimi, Charles, Zeggini, Eleftheria, and Sandhu, Manjinder S.

Published
2015
Full Text
View/download PDF

24. A global network for investigating the genomic epidemiology of malaria

Author

Achidi, Eric Akum, Agbenyega, Tsiri, Allen, Stephen, Amodu, Olukemi, Bojang, Kalifa, Conway, David, Corran, Patrick, Deloukas, Panos, Djimde, Abdoulaye, Dolo, Amagana, Doumbo, Ogobara, Drakeley, Chris, Duffy, Patrick, Dunstan, Sarah, Evans, Jennifer, Farrar, Jeremy, Fernando, Deepika, Hien, Tran Tinh, Horstmann, Rolf, Ibrahim, Muntaser, Karunaweera, Nadira, Kokwaro, Gilbert, Koram, Kojo, Kwiatkowski, Dominic, Lemnge, Martha, Makani, Julie, Marsh, Kevin, Michon, Pascal, Modiano, David, Molyneux, Malcolm E., Mueller, Ivo, Mutabingwa, Theonest, Peshu, Norbert, Plowe, Chris, Puijalon, Odile, Ragoussis, Jiannis, Reeder, John, Reyburn, Hugh, Riley, Eleanor, Rogers, Jane, Sakuntabhai, Anavaj, Singhasivanon, Pratap, Sirima, Sodiomon, Sirugo, Giorgio, Tall, Adama, Taylor, Terrie, Thera, Mahamadou, Troye-Blomberg, Marita, Williams, Tom, Wilson, Michael, Amenga-Etego, Lucas, Apinjoh, Tobias O., Bougouma, Edith, Dewasurendra, Rajika, Diakite, Mahamadou, Enimil, Anthony, Hussein, Ayman, Ishengoma, Deus, Jallow, Muminatou, Lin, Enmoore, Ly, Alioune, Mangano, Valentina D., Manjurano, Alphaxard, Manning, Laurens, Ndila, Carolyne M., Nyirongo, Vysaul, Oluoch, Tom, Quyen, Nguyen T. N., Suriyaphol, Prapat, Toure, Ousman, Kwiatkowski, Dominic, Alcock, Daniel, Auburn, Sarah, Barnwell, David, Bull, Susan, Campino, Susana, deVries, Jantina, Elzein, Abier, Evans, Julie, Fitzpatrick, Kathryn, Ghansah, Anita, Green, Angie, Hart, Lee, Hilton, Eliza, Hubbart, Christina, Hughes, Catherine, Jeffreys, Anna E., Kivinen, Katja, MacInnis, Bronwyn, Manske, Magnus, Maslen, Gareth, McCreight, Marilyn, Mendy, Alieu, Moyes, Catherine, Nyika, Aceme, Potter, Claire, Risley, Paul, Rowlands, Kate, SanJoaquin, Miguel, Small, Kerrin, Somaskantharajah, Elilan, Stevens, Marryat, Teo, YikYing, Watson, Renee, Carucci, Dan, Cook, Katharine, Doyle, Alan, Duombo, Ogobara, Gottlieb, Michael, Kwiatkowski, Dominic, Rockett, Kirk A., Vanderwal, Aaron, Clark, Taane, Parker, Michael, and Wrigley, Rebecca

Published
2008
Full Text
View/download PDF

25. Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

Author

Collier, D. A., De Marco, A., Ferreira, I. A. T. M., Meng, B., Datir, R. P., Walls, A. C., Kemp, S. A., Bassi, J., Pinto, D., Silacci-Fregni, C., Bianchi, S., Tortorici, M. A., Bowen, J., Culap, K., Jaconi, S., Cameroni, E., Snell, G., Pizzuto, M. S., Pellanda, A. F., Garzoni, C., Riva, A., Baker, S., Dougan, G., Hess, C., Kingston, N., Lehner, P. J., Lyons, P. A., Matheson, N. J., Owehand, W. H., Saunders, C., Summers, C., Thaventhiran, J. E. D., Toshner, M., Weekes, M. P., Bucke, A., Calder, J., Canna, L., Domingo, J., Elmer, A., Fuller, S., Harris, J., Hewitt, S., Kennet, J., Jose, S., Kourampa, J., Meadows, A., O'Brien, C., Price, J., Publico, C., Rastall, R., Ribeiro, C., Rowlands, J., Ruffolo, V., Tordesillas, H., Bullman, B., Dunmore, B. J., Fawke, S., Graf, S., Hodgson, J., Huang, C., Hunter, K., Jones, E., Legchenko, E., Matara, C., Martin, J., Mescia, F., O'Donnell, C., Pointon, L., Pond, N., Shih, J., Sutcliffe, R., Tilly, T., Treacy, C., Tong, Z., Wood, J., Wylot, M., Bergamaschi, L., Betancourt, A., Bower, G., Cossetti, C., De Sa, A., Epping, M., Grenfell, R., Hinch, A., Huhn, O., Jackson, S., Jarvis, I., Lewis, D., Marsden, J., Nice, F., Okecha, G., Omarjee, O., Perera, M., Richoz, N., Romashova, V., Yarkoni, N. S., Sharma, R., Stefanucci, L., Stephens, J., Strezlecki, M., Turner, L., De Bie, E. M. D. D., Bunclark, K., Josipovic, M., Mackay, M., Rossi, S., Selvan, M., Spencer, S., Yong, C., Ansaripour, A., Michael, A., Mwaura, L., Patterson, C., Polwarth, G., Polgarova, P., di Stefano, G., Fahey, C., Michel, R., Bong, S. -H., Coudert, J. D., Holmes, E., Allison, J., Butcher, H., Caputo, D., Clapham-Riley, D., Dewhurst, E., Furlong, A., Graves, B., Gray, J., Ivers, T., Kasanicki, M., Le Gresley, E., Linger, R., Meloy, S., Muldoon, F., Ovington, N., Papadia, S., Phelan, I., Stark, H., Stirrups, K. E., Townsend, P., Walker, N., Webster, J., Mccoy, L. E., Smith, K. G. C., Bradley, J. R., Temperton, N., Ceron-Gutierrez, L., Barcenas-Morales, G., Robson, S. C., Loman, N. J., Connor, T. R., Golubchik, T., Martinez Nunez, R. T., Ludden, C., Corden, S., Johnston, I., Bonsall, D., Smith, C. P., Awan, A. R., Bucca, G., Torok, M. E., Saeed, K., Prieto, J. A., Jackson, D. K., Hamilton, W. L., Snell, L. B., Moore, C., Harrison, E. M., Goncalves, S., Fairley, D. J., Loose, M. W., Watkins, J., Livett, R., Moses, S., Amato, R., Nicholls, S., Bull, M., Smith, D. L., Barrett, J., Aanensen, D. M., Curran, M. D., Parmar, S., Aggarwal, D., Shepherd, J. G., Parker, M. D., Glaysher, S., Bashton, M., Underwood, A. P., Pacchiarini, N., Loveson, K. F., Carabelli, A. M., Templeton, K. E., Langford, C. F., Sillitoe, J., de Silva, T. I., Wang, D., Kwiatkowski, D., Rambaut, A., O'Grady, J., Cottrell, S., Holden, M. T. G., Thomson, E. C., Osman, H., Andersson, M., Chauhan, A. J., Hassan-Ibrahim, M. O., Lawniczak, M., Alderton, A., Chand, M., Constantinidou, C., Unnikrishnan, M., Darby, A. C., Hiscox, J. A., Paterson, S., Martincorena, I., Robertson, D. L., Volz, E. M., Page, A. J., Pybus, O. G., Bassett, A. R., Ariani, C. V., Spencer Chapman, M. H., K. K., Li, Shah, R. N., Jesudason, N. G., Taha, Y., Mchugh, M. P., Dewar, R., Jahun, A. S., Mcmurray, C., Pandey, S., Mckenna, J. P., Nelson, A., Young, G. R., Mccann, C. M., Elliott, S., Lowe, H., Temperton, B., Roy, S., Price, A., Rey, S., Wyles, M., Rooke, S., Shaaban, S., de Cesare, M., Letchford, L., Silveira, S., Pelosi, E., Wilson-Davies, E., Hosmillo, M., O'Toole, A., Hesketh, A. R., Stark, R., du Plessis, L., Ruis, C., Adams, H., Bourgeois, Y., Michell, S. L., Gramatopoulos, D., Edgeworth, J., Breuer, J., Todd, J. A., Fraser, C., Buck, D., John, M., Kay, G. L., Palmer, S., Peacock, S. J., Heyburn, D., Weldon, D., Robinson, E., Mcnally, A., Muir, P., Vipond, I. B., Boyes, J., Sivaprakasam, V., Salluja, T., Dervisevic, S., Meader, E. J., Park, N. R., Oliver, K., Jeffries, A. R., Ott, S., da Silva Filipe, A., Simpson, D. A., Williams, C., Masoli, J. A. H., Knight, B. A., Jones, C. R., Koshy, C., Ash, A., Casey, A., Bosworth, A., Ratcliffe, L., Xu-McCrae, L., Pymont, H. M., Hutchings, S., Berry, L., Jones, K., Halstead, F., Davis, T., Holmes, C., Iturriza-Gomara, M., Lucaci, A. O., Randell, P. A., Cox, A., Madona, P., Harris, K. A., Brown, J. R., Mahungu, T. W., Irish-Tavares, D., Haque, T., Hart, J., Witele, E., Fenton, M. L., Liggett, S., Graham, C., Swindells, E., Collins, J., Eltringham, G., Campbell, S., Mcclure, P. C., Clark, G., Sloan, T. J., Jones, C., Lynch, J., Warne, B., Leonard, S., Durham, J., Williams, T., Haldenby, S. T., Storey, N., Alikhan, N. -F., Holmes, N., Carlile, M., Perry, M., Craine, N., Lyons, R. A., Beckett, A. H., Goudarzi, S., Fearn, C., Cook, K., Dent, H., Paul, H., Davies, R., Blane, B., Girgis, S. T., Beale, M. A., Bellis, K. L., Dorman, M. J., Drury, E., Kane, L., Kay, S., Mcguigan, S., Nelson, R., Prestwood, L., Rajatileka, S., Batra, R., Williams, R. J., Kristiansen, M., Green, A., Justice, A., Mahanama, A. I. K., Samaraweera, B., Hadjirin, N. F., Quick, J., Poplawski, R., Kermack, L. M., Reynolds, N., Hall, G., Chaudhry, Y., Pinckert, M. L., Georgana, I., Moll, R. J., Thornton, A., Myers, R., Stockton, J., Williams, C. A., Yew, W. C., Trotter, A. J., Trebes, A., MacIntyre-Cockett, G., Birchley, A., Adams, A., Plimmer, A., Gatica-Wilcox, B., Mckerr, C., Hilvers, E., Jones, H., Asad, H., Coombes, J., Evans, J. M., Fina, L., Gilbert, L., Graham, L., Cronin, M., Kumziene-Summerhayes, S., Taylor, S., Jones, S., Groves, D. C., Zhang, P., Gallis, M., Louka, S. F., Starinskij, I., Jackson, C., Gourtovaia, M., Tonkin-Hill, G., Lewis, K., Tovar-Corona, J. M., James, K., Baxter, L., Alam, M. T., Orton, R. J., Hughes, J., Vattipally, S., Ragonnet-Cronin, M., Nascimento, F. F., Jorgensen, D., Boyd, O., Geidelberg, L., Zarebski, A. E., Raghwani, J., Kraemer, M. U. G., Southgate, J., Lindsey, B. B., Freeman, T. M., Keatley, J. -P., Singer, J. B., de Oliveira Martins, L., Yeats, C. A., Abudahab, K., Taylor, B. E. W., Menegazzo, M., Danesh, J., Hogsden, W., Eldirdiri, S., Kenyon, A., Mason, J., Robinson, T. I., Holmes, A., Hartley, J. A., Curran, T., Mather, A. E., Shankar, G., Jones, R., Howe, R., Morgan, S., Wastenge, E., Chapman, M. R., Mookerjee, S., Stanley, R., Smith, W., Peto, T., Eyre, D., Crook, D., Vernet, G., Kitchen, C., Gulliver, H., Merrick, I., Guest, M., Munn, R., Bradley, D. T., Wyatt, T., Beaver, C., Foulser, L., Churcher, C. M., Brooks, E., Smith, K. S., Galai, K., Mcmanus, G. M., Bolt, F., Coll, F., Meadows, L., Attwood, S. W., Davies, A., De Lacy, E., Downing, F., Edwards, S., Scarlett, G. P., Jeremiah, S., Smith, N., Leek, D., Sridhar, S., Forrest, S., Cormie, C., Gill, H. K., Dias, J., Higginson, E. E., Maes, M., Young, J., Wantoch, M., Jamrozy, D., Lo, S., Patel, M., Hill, V., Bewshea, C. M., Ellard, S., Auckland, C., Harrison, I., Bishop, C., Chalker, V., Richter, A., Beggs, A., Best, A., Percival, B., Mirza, J., Megram, O., Mayhew, M., Crawford, L., Ashcroft, F., Moles-Garcia, E., Cumley, N., Hopes, R., Asamaphan, P., Niebel, M. O., Gunson, R. N., Bradley, A., Maclean, A., Mollett, G., Blacow, R., Bird, P., Helmer, T., Fallon, K., Tang, J., Hale, A. D., Macfarlane-Smith, L. R., Harper, K. L., Carden, H., Machin, N. W., Jackson, K. A., Ahmad, S. S. Y., George, R. P., Turtle, L., O'Toole, E., Watts, J., Breen, C., Cowell, A., Alcolea-Medina, A., Charalampous, T., Patel, A., Levett, L. J., Heaney, J., Rowan, A., Taylor, G. P., Shah, D., Atkinson, L., Lee, J. C. D., Westhorpe, A. P., Jannoo, R., Lowe, H. L., Karamani, A., Ensell, L., Chatterton, W., Pusok, M., Dadrah, A., Symmonds, A., Sluga, G., Molnar, Z., Baker, P., Bonner, S., Essex, S., Barton, E., Padgett, D., Scott, G., Greenaway, J., Payne, B. A. I., Burton-Fanning, S., Waugh, S., Raviprakash, V., Sheriff, N., Blakey, V., Williams, L. -A., Moore, J., Stonehouse, S., Smith, L., Davidson, R. K., Bedford, L., Coupland, L., Wright, V., Chappell, J. G., Tsoleridis, T., Ball, J., Khakh, M., Fleming, V. M., Lister, M. M., Howson-Wells, H. C., Boswell, T., Joseph, A., Willingham, I., Duckworth, N., Walsh, S., Wise, E., Moore, N., Mori, M., Cortes, N., Kidd, S., Williams, R., Gifford, L., Bicknell, K., Wyllie, S., Lloyd, A., Impey, R., Malone, C. S., Cogger, B. J., Levene, N., Monaghan, L., Keeley, A. J., Partridge, D. G., Raza, M., Evans, C., Johnson, K., Betteridge, E., Farr, B. W., Goodwin, S., Quail, M. A., Scott, C., Shirley, L., Thurston, S. A. J., Rajan, D., Bronner, I. F., Aigrain, L., Redshaw, N. M., Lensing, S. V., Mccarthy, S., Makunin, A., Balcazar, C. E., Gallagher, M. D., Williamson, K. A., Stanton, T. D., Michelsen, M. L., Warwick-Dugdale, J., Manley, R., Farbos, A., Harrison, J. W., Sambles, C. M., Studholme, D. J., Lackenby, A., Mbisa, T., Platt, S., Miah, S., Bibby, D., Manso, C., Hubb, J., Dabrera, G., Ramsay, M., Bradshaw, D., Schaefer, U., Groves, N., Gallagher, E., Lee, D., Williams, D., Ellaby, N., Hartman, H., Manesis, N., Patel, V., Ledesma, J., Twohig, K. A., Allara, E., Pearson, C., Cheng, J. K. J., Bridgewater, H. E., Frost, L. R., Taylor-Joyce, G., Brown, P. E., Tong, L., Broos, A., Mair, D., Nichols, J., Carmichael, S. N., Smollett, K. L., Nomikou, K., Aranday-Cortes, E., Johnson, N., Nickbakhsh, S., Vamos, E. E., Hughes, M., Rainbow, L., Eccles, R., Nelson, C., Whitehead, M., Gregory, R., Gemmell, M., Wierzbicki, C., Webster, H. J., Fisher, C. L., Signell, A. W., Betancor, G., Wilson, H. D., Nebbia, G., Flaviani, F., Cerda, A. C., Merrill, T. V., Wilson, R. E., Cotic, M., Bayzid, N., Thompson, T., Acheson, E., Rushton, S., O'Brien, S., Baker, D. J., Rudder, S., Aydin, A., Sang, F., Debebe, J., Francois, S., Vasylyeva, T. I., Zamudio, M. E., Gutierrez, B., Marchbank, A., Maksimovic, J., Spellman, K., Mccluggage, K., Morgan, M., Beer, R., Afifi, S., Workman, T., Fuller, W., Bresner, C., Angyal, A., Green, L. R., Parsons, P. J., Tucker, R. M., Brown, R., Whiteley, M., Bonfield, J., Puethe, C., Whitwham, A., Liddle, J., Rowe, W., Siveroni, I., Le-Viet, T., Gaskin, A., Johnson, R., Abnizova, I., Ali, M., Allen, L., Anderson, R., Ariani, C., Austin-Guest, S., Bala, S., Bassett, A., Battleday, K., Beal, J., Beale, M., Bellany, S., Bellerby, T., Bellis, K., Berger, D., Berriman, M., Bevan, P., Binley, S., Bishop, J., Blackburn, K., Boughton, N., Bowker, S., Brendler-Spaeth, T., Bronner, I., Brooklyn, T., Buddenborg, S. K., Bush, R., Caetano, C., Cagan, A., Carter, N., Cartwright, J., Monteiro, T. C., Chapman, L., Chillingworth, T. -J., Clapham, P., Clark, R., Clarke, A., Clarke, C., Cole, D., Cook, E., Coppola, M., Cornell, L., Cornwell, C., Corton, C., Crackett, A., Cranage, A., Craven, H., Craw, S., Crawford, M., Cutts, T., Dabrowska, M., Davies, M., Dawson, J., Day, C., Densem, A., Dibling, T., Dockree, C., Dodd, D., Dogga, S., Dougherty, M., Dove, A., Drummond, L., Dudek, M., Durrant, L., Easthope, E., Eckert, S., Ellis, P., Farr, B., Fenton, M., Ferrero, M., Flack, N., Fordham, H., Forsythe, G., Francis, M., Fraser, A., Freeman, A., Galvin, A., Garcia-Casado, M., Gedny, A., Girgis, S., Glover, J., Gould, O., Gray, A., Gray, E., Griffiths, C., Gu, Y., Guerin, F., Hamilton, W., Hanks, H., Harrison, E., Harrott, A., Harry, E., Harvison, J., Heath, P., Hernandez-Koutoucheva, A., Hobbs, R., Holland, D., Holmes, S., Hornett, G., Hough, N., Huckle, L., Hughes-Hallet, L., Hunter, A., Inglis, S., Iqbal, S., Jackson, A., Jackson, D., Verdejo, C. J., Jones, M., Kallepally, K., Kay, K., Keatley, J., Keith, A., King, A., Kitchin, L., Kleanthous, M., Klimekova, M., Korlevic, P., Krasheninnkova, K., Lane, G., Langford, C., Laverack, A., Law, K., Lensing, S., Lewis-Wade, A., Lin, Q., Lindsay, S., Linsdell, S., Long, R., Lovell, J., Mack, J., Maddison, M., Mamun, I., Mansfield, J., Marriott, N., Martin, M., Mayho, M., Mcclintock, J., Mchugh, S., Mcminn, L., Meadows, C., Mobley, E., Moll, R., Morra, M., Morrow, L., Murie, K., Nash, S., Nathwani, C., Naydenova, P., Neaverson, A., Nerou, E., Nicholson, J., Nimz, T., Noell, G. G., O'Meara, S., Ohan, V., Olney, C., Ormond, D., Oszlanczi, A., Pang, Y. F., Pardubska, B., Park, N., Parmar, A., Patel, G., Payne, M., Peacock, S., Petersen, A., Plowman, D., Preston, T., Quail, M., Rance, R., Rawlings, S., Redshaw, N., Reynolds, J., Reynolds, M., Rice, S., Richardson, M., Roberts, C., Robinson, K., Robinson, M., Robinson, D., Rogers, H., Rojo, E. M., Roopra, D., Rose, M., Rudd, L., Sadri, R., Salmon, N., Saul, D., Schwach, F., Seekings, P., Simms, A., Sinnott, M., Sivadasan, S., Siwek, B., Sizer, D., Skeldon, K., Skelton, J., Slater-Tunstill, J., Sloper, L., Smerdon, N., Smith, C., Smith, J., Smith, K., Smith, M., Smith, S., Smith, T., Sneade, L., Soria, C. D., Sousa, C., Souster, E., Sparkes, A., Spencer-Chapman, M., Squares, J., Steed, C., Stickland, T., Still, I., Stratton, M., Strickland, M., Swann, A., Swiatkowska, A., Sycamore, N., Swift, E., Symons, E., Szluha, S., Taluy, E., Tao, N., Taylor, K., Thompson, S., Thompson, M., Thomson, M., Thomson, N., Thurston, S., Toombs, D., Topping, B., Tovar-Corona, J., Ungureanu, D., Uphill, J., Urbanova, J., Van, P. J., Vancollie, V., Voak, P., Walker, D., Walker, M., Waller, M., Ward, G., Weatherhogg, C., Webb, N., Wells, A., Wells, E., Westwood, L., Whipp, T., Whiteley, T., Whitton, G., Widaa, S., Williams, M., Wilson, M., Wright, S., Harvey, W., Virgin, H. W., Lanzavecchia, A., Piccoli, L., Doffinger, R., Wills, M., Veesler, D., Corti, D., and Gupta, R. K.

Subjects
0301 basic medicine, Male, Models, Molecular, Passive, Antibodies, Viral, Neutralization, 0302 clinical medicine, Models, Monoclonal, 80 and over, Viral, Neutralizing antibody, Neutralizing, Aged, 80 and over, Vaccines, Vaccines, Synthetic, Multidisciplinary, biology, Antibodies, Monoclonal, C500, Middle Aged, C700, Spike Glycoprotein, Vaccination, Spike Glycoprotein, Coronavirus, Female, Angiotensin-Converting Enzyme 2, Antibody, Aged, Antibodies, Neutralizing, COVID-19, COVID-19 Vaccines, HEK293 Cells, Humans, Immune Evasion, Immunization, Passive, Mutation, Neutralization Tests, SARS-CoV-2, medicine.drug_class, B100, Monoclonal antibody, Antibodies, Virus, 03 medical and health sciences, Immune system, medicine, COVID-19 Serotherapy, QR355, Synthetic, Molecular, Virology, Coronavirus, 030104 developmental biology, Immunization, biology.protein, 030217 neurology & neurosurgery
Abstract

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

Published
2021

26. High-fidelity laser-free universal control of trapped ion qubits

Author

Srinivas, R., primary, Burd, S. C., additional, Knaack, H. M., additional, Sutherland, R. T., additional, Kwiatkowski, A., additional, Glancy, S., additional, Knill, E., additional, Wineland, D. J., additional, Leibfried, D., additional, Wilson, A. C., additional, Allcock, D. T. C., additional, and Slichter, D. H., additional

Published
2021
Full Text
View/download PDF

27. Arctic Ocean annual high in pCO2 could shift from winter to summer.

Author

Orr, James C., Kwiatkowski, Lester, and Pörtner, Hans-Otto

Abstract

Long-term stress on marine organisms from ocean acidification will differ between seasons. As atmospheric carbon dioxide (CO2) increases, so do seasonal variations of ocean CO2 partial pressure ( p CO 2 ), causing summer and winter long-term trends to diverge1–5. Trends may be further influenced by an unexplored factor—changes in the seasonal timing of p CO 2 . In Arctic Ocean surface waters, the observed timing is typified by a winter high and summer low6 because biological effects dominate thermal effects. Here we show that 27 Earth system models simulate similar timing under historical forcing but generally project that the summer low, relative to the annual mean, eventually becomes a high across much of the Arctic Ocean under mid-to-high-level CO2 emissions scenarios. Often the greater increase in summer p CO 2 , although gradual, abruptly inverses the chronological order of the annual high and low, a phenomenon not previously seen in climate-related variables. The main cause is the large summer sea surface warming7 from earlier retreat of seasonal sea ice8. Warming and changes in other drivers enhance this century’s increase in extreme summer p CO 2 by 29 ± 9 per cent compared with no change in driver seasonalities. Thus the timing change worsens summer ocean acidification, which in turn may lower the tolerance of endemic marine organisms to increasing summer temperatures.Simulations suggest that the partial pressure of carbon dioxide in the Arctic Ocean will shift from a winter to a summer maximum owing to enhanced summer sea surface warming from earlier sea-ice retreat. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

28. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Author

Burton, Paul R., Clayton, David G., Cardon, Lon R., Craddock, Nick, Deloukas, Panos, Duncanson, Audrey, Kwiatkowski, Dominic P., McCarthy, Mark I., Ouwehand, Willem H., Samani, Nilesh J., Todd, John A., Donnelly, Peter, Barrett, Jeffrey C., Davison, Dan, Easton, Doug, Evans, David, Leung, Hin-Tak, Marchini, Jonathan L., Morris, Andrew P., Spencer, Chris C. A., Tobin, Martin D., Attwood, Antony P., Boorman, James P., Cant, Barbara, Everson, Ursula, Hussey, Judith M., Jolley, Jennifer D., Knight, Alexandra S., Koch, Kerstin, Meech, Elizabeth, Nutland, Sarah, Prowse, Christopher V., Stevens, Helen E., Taylor, Niall C., Walters, Graham R., Walker, Neil M., Watkins, Nicholas A., Winzer, Thilo, Jones, Richard W., McArdle, Wendy L., Ring, Susan M., Strachan, David P., Pembrey, Marcus, Breen, Gerome, St Clair, David, Caesar, Sian, Gordon-Smith, Katherine, Jones, Lisa, Fraser, Christine, Green, Elaine K., Grozeva, Detelina, Hamshere, Marian L., Holmans, Peter A., Jones, Ian R., Kirov, George, Moskvina, Valentina, Nikolov, Ivan, O'Donovan, Michael C., Owen, Michael J., Collier, David A., Elkin, Amanda, Farmer, Anne, Williamson, Richard, McGuffin, Peter, Young, Allan H., Ferrier, I. Nicol, Ball, Stephen G., Balmforth, Anthony J., Barrett, Jennifer H., Bishop, D. Timothy, Iles, Mark M., Maqbool, Azhar, Yuldasheva, Nadira, Hall, Alistair S., Braund, Peter S., Dixon, Richard J., Mangino, Massimo, Stevens, Suzanne, Thompson, John R., Bredin, Francesca, Tremelling, Mark, Parkes, Miles, Drummond, Hazel, Lees, Charles W., Nimmo, Elaine R., Satsangi, Jack, Fisher, Sheila A., Forbes, Alastair, Lewis, Cathryn M., Onnie, Clive M., Prescott, Natalie J., Sanderson, Jeremy, Mathew, Christopher G., Barbour, Jamie, Mohiuddin, M. Khalid, Todhunter, Catherine E., Mansfield, John C., Ahmad, Tariq, Cummings, Fraser R., Jewell, Derek P., Webster, John, Brown, Morris J., Lathrop, G. Mark, Connell, John, Dominiczak, Anna, Marcano, Carolina A. Braga, Burke, Beverley, Dobson, Richard, Gungadoo, Johannie, Lee, Kate L., Munroe, Patricia B., Newhouse, Stephen J., Onipinla, Abiodun, Wallace, Chris, Xue, Mingzhan, Caulfield, Mark, Farrall, Martin, Barton, Anne, Bruce, Ian N., Donovan, Hannah, Eyre, Steve, Gilbert, Paul D., Hider, Samantha L., Hinks, Anne M., John, Sally L., Potter, Catherine, Silman, Alan J., Symmons, Deborah P. M., Thomson, Wendy, Worthington, Jane, Dunger, David B., Widmer, Barry, Frayling, Timothy M., Freathy, Rachel M., Lango, Hana, Perry, John R. B., Shields, Beverley M., Weedon, Michael N., Hattersley, Andrew T., Hitman, Graham A., Walker, Mark, Elliott, Kate S., Groves, Christopher J., Lindgren, Cecilia M., Rayner, Nigel W., Timpson, Nicholas J., Zeggini, Eleftheria, Newport, Melanie, Sirugo, Giorgio, Lyons, Emily, Vannberg, Fredrik, Hill, Adrian V. S., Bradbury, Linda A., Farrar, Claire, Pointon, Jennifer J., Wordsworth, Paul, Brown, Matthew A., Franklyn, Jayne A., Heward, Joanne M., Simmonds, Matthew J., Gough, Stephen C. L., Seal, Sheila, Stratton, Michael R., Rahman, Nazneen, Ban, Maria, Goris, An, Sawcer, Stephen J., Compston, Alastair, Conway, David, Jallow, Muminatou, Rockett, Kirk A., Bumpstead, Suzannah J., Chaney, Amy, Downes, Kate, Ghori, Mohammed J. R., Gwilliam, Rhian, Hunt, Sarah E., Inouye, Michael, Keniry, Andrew, King, Emma, McGinnis, Ralph, Potter, Simon, Ravindrarajah, Rathi, Whittaker, Pamela, Widden, Claire, Withers, David, Cardin, Niall J., Ferreira, Teresa, Pereira-Gale, Joanne, Hallgrimsdottir, Ingileif B., Howie, Bryan N., Su, Zhan, Teo, Yik Ying, Vukcevic, Damjan, Bentley, David, and Compston, Alistair

Abstract

Author(s): The Wellcome Trust Case Control Consortium; Management Committee; Paul R. Burton [1]; David G. Clayton [2]; Lon R. Cardon [3]; Nick Craddock [4]; Panos Deloukas [5]; Audrey Duncanson [6]; [...]

Published
2007
Full Text
View/download PDF

29. Comprehensive molecular characterization of urothelial bladder carcinoma

Author

Weinstein, John N., Akbani, Rehan, Broom, Bradley M., Wang, Wenyi, Verhaak, Roeland G. W., McConkey, David, Lerner, Seth, Morgan, Margaret, Creighton, Chad J., Smith, Carolyn, Kwiatkowski, David J., Cherniack, Andrew D., Kim, Jaegil, Pedamallu, Chandra Sekhar, Noble, Michael S., Al-Ahmadie, Hikmat A., Reuter, Victor E., Rosenberg, Jonathan E., Bajorin, Dean F., Bochner, Bernard H., Solit, David B., Koppie, Theresa, Robinson, Brian, Gordenin, Dmitry A., Fargo, David, Klimczak, Leszek J., Roberts, Steven A., Au, Jessie, Laird, Peter W., Hinoue, Toshinori, Schultz, Nikolaus, Ramirez, Ricardo, Hansel, Donna, Hoadley, Katherine A., Kim, William Y., Damrauer, Jeffrey S., Baylin, Stephen B., Mungall, Andrew J., Robertson, Gordon A., Chu., Andy, Sougnez, Carrie, Cibulskis, Kristian, Lichtenstein, Lee, Sivachenko, Andrey, Stewart, Chip, Lawrence, Michael S., Getz, Gad, Lander, Eric, Gabriel., Stacey B., Donehower, Lawrence, Carter, Scott L., Saksena, Gordon, Schumacher, Steven E., Freeman, Samuel S., Jung, Joonil, Bhatt, Ami S., Pugh, Trevor, Beroukhim, Rameen, Gabriel, Stacey B., Meyerson, Matthew, Chu, Andy, Ally, Adrian, Balasundaram, Miruna, Butterfield, Yaron S. N., Dhalla, Noreen, Hirst, Carrie, Holt, Robert A., Jones, Steven J. M., Lee, Darlene, Li, Haiyan I., Marra, Marco A., Mayo, Michael, Moore, Richard A., Schein, Jacqueline E., Sipahimalani, Payal, Tam, Angela, Thiessen, Nina, Wong, Tina, Wye, Natasja, Bowlby, Reanne, Chuah, Eric, Guin, Ranabir, Shen, Hui, Bootwalla, Moiz S., Jr, Timothy Triche, Lai, Phillip H., Van Den Berg, David J., Weisenberger, Daniel J., Balu, Saianand, Bodenheimer, Tom, Damrauer Alan P. Hoyle, Jeffrey S., Jefferys, Stuart R., Meng, Shaowu, Mose, Lisle E., Simons, Janae V., Soloway, Mathew G., Wu, Junyuan, Parker, Joel S., Hayes, Neil D., Roach, Jeffrey, Buda, Elizabeth, Jones, Corbin D., Mieczkowski, Piotr A., Tan, Donghui, Veluvolu, Umadevi, Waring, Scot, Auman, Todd J., Perou, Charles M., Wilkerson, Matthew D., Santoso, Netty, Parfenov, Michael, Ren, Xiaojia, Pantazi, Angeliki, Hadjipanayis, Angela, Seidman, Jonathan, Kucherlapati, Raju, Lee, Semin, Yang, Lixing, Park, Peter J., Xu, Andrew Wei, Protopopov, Alexei, Zhang, Jianhua, Bristow, Christopher, Mahadeshwar, Harshad S., Seth, Sahil, Song, Xingzhi, Tang, Jiabin, Zeng, Dong, Chin, Lynda, Guo, Charles, Casasent, Tod D., Liu, Wenbin, Ju, Zhenlin, Motter, Thomas, Peng, Bo, Ryan, Michael, Su, Xiaoping, Yang, Ji-Yeon, Lorenzi, Philip L., Yao, Hui, Zhang, Nianxiang, Zhang, Jiexin, Mills, Gordon B., Cho, Juok, DiCara, Daniel, Frazer, Scott, Gehlenborg, Nils, Heiman, David I., Lin, Pei, Liu, Yingchun, Stojanov, Petar, Voet, Doug, Zhang, Hailei, Zou, Lihua, Bernard, Brady, Kreisberg, Dick, Reynolds, Sheila, Rovira, Hector, Shmulevich, Ilya, Gao, Jianjiong, Jacobsen, Anders, Aksoy, Arman B., Antipin, Yevgeniy, Ciriello, Giovanni, Dresdner, Gideon, Gross, Benjamin, Lee, William, Reva, Boris, Shen, Ronglai, Sinha, Rileen, Sumer, Onur S., Weinhold, Nils, Ladanyi, Marc, Sander, Chris, Benz, Christopher, Carlin, Daniel, Haussler, David, Ng, Sam, Paull, Evan O., Stuart, Joshua, Zhu, Jing, Liu, Yuexin, Zhang, Wei, Taylor, Barry S., Lichtenberg, Tara M., Zmuda, Erik, Barr, Thomas, Black, Aaron D., George, Myra, Hanf, Benjamin, Helsel, Carmen, McAllister, Cynthia, Ramirez, Nilsa C., Tabler, Teresa R., Weaver, Stephanie, Wise, Lisa, Bowen, Jay, Gastier-Foster, Julie M., Jian, Weiguo, Tello, Sebrina, Ittman, Michael, Castro, Patricia, McClenden, Whitney D., Gibbs, Richard, Saller, Charles, Tarvin, Katherine, DiPiero, Jennifer M., Owens, Jennifer, Bollag, Roni, Li, Qiang, Weinberger, Paul, Czerwinski, Christine, Huelsenbeck-Dill, Lori, Iacocca, Mary, Petrelli, Nicholas, Rabeno, Brenda, Swanson, Pat, Shelton, Troy, Curley, Erin, Gardner, Johanna, Mallery, David, Penny, Robert, Van Bang, Nguyen, Thi Hanh, Phan, Kohl, Bernard, Van Le, Xuan, Duc Phu, Bui, Thorp, Richard, Tien, Nguyen Viet, Vinh, Le Quang, Sandusky, George, Burks, Eric, Christ, Kimberly, Gee, Jason, Holway, Antonia, Moinzadeh, Alireza, Sorcini, Andrea, Sullivan, Travis, Garcia-Grossman, Ilana R., Regazzi, Ashley M., Boice, Lori, Rathmell, Wendy Kimryn, Thorne, Leigh, Bastacky, Sheldon, Davies, Benjamin, Dhir, Rajiv, Gingrich, Jeffrey, Hrebinko, Ronald, Maranchie, Jodi, Nelson, Joel, Parwani, Anil, Bshara, Wiam, Gaudioso, Carmelo, Morrison, Carl, Alexopoulou, Vina, Bartlett, John, Engel, Jay, Kodeeswaran, Sugy, Antic, Tatjana, O’Donnell, Peter H., Smith, Norm D., Steinberg, Gary D., Egea, Sophie, Gomez-Fernandez, Carmen, Herbert, Lynn, Jorda, Merce, Soloway, Mark, Beaver, Allison, Carter, Suzie, Kapur, Payal, Lewis, Cheryl, Lotan, Yair, Bondaruk, Jolanta, Czerniak, Bogdan, Skinner, Eila, Aldape, Kenneth, Jensen, Mark A., Kahn, Ari B., Pihl, Todd D., Pot, David A., Srinivasan, Deepak, Wan, Yunhu, Ferguson, Martin L., Zenklusen, Jean Claude, Davidsen, Tanja, Demchok, John A., Mills Shaw, Kenna R., Sheth, Margi, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Hutter, Carolyn, Ozenberger, Bradley A., Sofia, Heidi J., and Eley, Greg

Published
2014
Full Text
View/download PDF

30. Structural basis of BMP signalling inhibition by the cystine knot protein Noggin

Author

Groppe, Jay, Greenwald, Jason, Wiater, Ezra, Rodriguez-Leon, Joaquin, Economides, Aris N., Kwiatkowski, Witek, Affolter, Markus, Vale, Wylie W., Belmonte, Juan Carlos Izpisua, and Choe, Senyon

Abstract

Author(s): Jay Groppe [1, 2]; Jason Greenwald [1]; Ezra Wiater [3]; Joaquin Rodriguez-Leon [4]; Aris N. Economides [5]; Witek Kwiatkowski [1]; Markus Affolter [2]; Wylie W. Vale [3]; Juan Carlos [...]

Published
2002
Full Text
View/download PDF

31. Resource-based niches provide a basis for plant species diversity and dominance in arctic tundra

Author

McKane, Robert B., Johnson, Loretta C., Shaver, Gaius R., Nadelhoffer, Knute J., Rastetter, Edward B., Fry, Brian, Giblin, Anne E., Kielland, Knut, Kwiatkowski, Bonnie L., Laundre, James A., and Murray, Georgia

Subjects
Research, Tundra ecology -- Research, Biodiversity -- Research, Species (Biology) -- Research, Biological diversity -- Research, Species -- Research
Abstract

Author(s): Robert B. McKane (corresponding author) [1]; Loretta C. Johnson [2]; Gaius R. Shaver [3]; Knute J. Nadelhoffer [3]; Edward B. Rastetter [3]; Brian Fry [4]; Anne E. Giblin [3]; [...]

Published
2002
Full Text
View/download PDF

32. Comprehensive genomic characterization of squamous cell lung cancers

Author

Hammerman, Peter S., Lawrence, Michael S., Voet, Douglas, Jing, Rui, Cibulskis, Kristian, Sivachenko, Andrey, Stojanov, Petar, McKenna, Aaron, Lander, Eric S., Gabriel, Stacey, Getz, Gad, Sougnez, Carrie, Imielinski, Marcin, Helman, Elena, Hernandez, Bryan, Pho, Nam H., Meyerson, Matthew, Chu, Andy, Chun, Hye-Jung E., Mungall, Andrew J., Pleasance, Erin, Gordon Robertson, A., Sipahimalani, Payal, Stoll, Dominik, Balasundaram, Miruna, Birol, Inanc, Butterfield, Yaron S. N., Chuah, Eric, Coope, Robin J. N., Corbett, Richard, Dhalla, Noreen, Guin, Ranabir, He, An, Hirst, Carrie, Hirst, Martin, Holt, Robert A., Lee, Darlene, Li, Haiyan I., Mayo, Michael, Moore, Richard A., Mungall, Karen, Ming Nip, Ka, Olshen, Adam, Schein, Jacqueline E., Slobodan, Jared R., Tam, Angela, Thiessen, Nina, Varhol, Richard, Zeng, Thomas, Zhao, Yongjun, Jones, Steven J. M., Marra, Marco A., Saksena, Gordon, Cherniack, Andrew D., Schumacher, Stephen E., Tabak, Barbara, Carter, Scott L., Nguyen, Huy, Onofrio, Robert C., Crenshaw, Andrew, Ardlie, Kristin, Beroukhim, Rameen, Winckler, Wendy, Protopopov, Alexei, Zhang, Jianhua, Hadjipanayis, Angela, Lee, Semin, Xi, Ruibin, Yang, Lixing, Ren, Xiaojia, Zhang, Hailei, Shukla, Sachet, Chen, Peng-Chieh, Haseley, Psalm, Lee, Eunjung, Chin, Lynda, Park, Peter J., Kucherlapati, Raju, Socci, Nicholas D., Liang, Yupu, Schultz, Nikolaus, Borsu, Laetitia, Lash, Alex E., Viale, Agnes, Sander, Chris, Ladanyi, Marc, Todd Auman, J., Hoadley, Katherine A., Wilkerson, Matthew D., Shi, Yan, Liquori, Christina, Meng, Shaowu, Li, Ling, Turman, Yidi J., Topal, Michael D., Tan, Donghui, Waring, Scot, Buda, Elizabeth, Walsh, Jesse, Jones, Corbin D., Mieczkowski, Piotr A., Singh, Darshan, Wu, Junyuan, Gulabani, Anisha, Dolina, Peter, Bodenheimer, Tom, Hoyle, Alan P., Simons, Janae V., Soloway, Matthew G., Mose, Lisle E., Jefferys, Stuart R., Balu, Saianand, OʼConnor, Brian D., Prins, Jan F., Liu, Jinze, Chiang, Derek Y., Neil Hayes, D., Perou, Charles M., Cope, Leslie, Danilova, Ludmila, Weisenberger, Daniel J., Maglinte, Dennis T., Pan, Fei, Van Den Berg, David J., Triche, Timothy, Jr, Herman, James G., Baylin, Stephen B., Laird, Peter W., Noble, Michael, Voet, Doug, Gehlenborg, Nils, DiCara, Daniel, Zhang, Jinhua, Wu, Chang-Jiun, Yingchun Liu, Spring, Zou, Lihua, Lin, Pei, Cho, Juok, Nazaire, Marc-Danie, Robinson, Jim, Thorvaldsdottir, Helga, Mesirov, Jill, Sinha, Rileen, Ciriello, Giovanni, Cerami, Ethan, Gross, Benjamin, Jacobsen, Anders, Gao, Jianjiong, Arman Aksoy, B., Weinhold, Nils, Ramirez, Ricardo, Taylor, Barry S., Antipin, Yevgeniy, Reva, Boris, Shen, Ronglai, Mo, Qianxing, Seshan, Venkatraman, Paik, Paul K., Akbani, Rehan, Zhang, Nianxiang, Broom, Bradley M., Casasent, Tod, Unruh, Anna, Wakefield, Chris, Craig Cason, R., Baggerly, Keith A., Weinstein, John N., Haussler, David, Benz, Christopher C., Stuart, Joshua M., Zhu, Jingchun, Szeto, Christopher, Scott, Gary K., Yau, Christina, Ng, Sam, Goldstein, Ted, Waltman, Peter, Sokolov, Artem, Ellrott, Kyle, Collisson, Eric A., Zerbino, Daniel, Wilks, Christopher, Ma, Singer, Craft, Brian, Du, Ying, Cabanski, Christopher, Walter, Vonn, Marron, J. S., Liu, Yufeng, Wang, Kai, Creighton, Chad J., Zhang, Yiqun, Travis, William D., Rekhtman, Natasha, Yi, Joanne, Aubry, Marie C., Cheney, Richard, Dacic, Sanja, Flieder, Douglas, Funkhouser, William, Illei, Peter, Myers, Jerome, Tsao, Ming-Sound, Penny, Robert, Mallery, David, Shelton, Troy, Hatfield, Martha, Morris, Scott, Yena, Peggy, Shelton, Candace, Sherman, Mark, Paulauskis, Joseph, Govindan, Ramaswamy, Azodo, Ijeoma, Beer, David, Bose, Ron, Byers, Lauren A., Carbone, David, Chang, Li-Wei, Chiang, Derek, Chun, Elizabeth, Collisson, Eric, Ding, Li, Heymach, John, Ida, Cristiane, Johnson, Bruce, Jurisica, Igor, Kaufman, Jacob, Kosari, Farhad, Kwiatkowski, David, Maher, Christopher A., Mungall, Andy, Pao, William, Peifer, Martin, Robertson, Gordon, Rusch, Valerie, Siegfried, Jill, Stuart, Joshua, Thomas, Roman K., Tomaszek, Sandra, Vaske, Charles, Weisenberger, Daniel, Wigle, Dennis A., Yang, Ping, John Zhang, Jianjua, Jensen, Mark A., Sfeir, Robert, Kahn, Ari B., Chu, Anna L., Kothiyal, Prachi, Wang, Zhining, Snyder, Eric E., Pontius, Joan, Pihl, Todd D., Ayala, Brenda, Backus, Mark, Walton, Jessica, Baboud, Julien, Berton, Dominique L., Nicholls, Matthew C., Srinivasan, Deepak, Raman, Rohini, Girshik, Stanley, Kigonya, Peter A., Alonso, Shelley, Sanbhadti, Rashmi N., Barletta, Sean P., Greene, John M., Pot, David A., Bandarchi-Chamkhaleh, Bizhan, Boyd, Jeff, Weaver, JoEllen, Azodo, Ijeoma A., Tomaszek, Sandra C., Christine Aubry, Marie, Ida, Christiane M., Brock, Malcolm V., Rogers, Kristen, Rutledge, Marian, Brown, Travis, Lee, Beverly, Shin, James, Trusty, Dante, Dhir, Rajiv, Siegfried, Jill M., Potapova, Olga, Fedosenko, Konstantin V., Nemirovich-Danchenko, Elena, Zakowski, Maureen, Iacocca, Mary V., Brown, Jennifer, Rabeno, Brenda, Czerwinski, Christine, Petrelli, Nicholas, Fan, Zhen, Todaro, Nicole, Eckman, John, Rathmell, Kimryn W., Thorne, Leigh B., Huang, Mei, Boice, Lori, Hill, Ashley, Curley, Erin, Morrison, Carl, Gaudioso, Carmelo, Bartlett, John M. S., Kodeeswaran, Sugy, Zanke, Brent, Sekhon, Harman, David, Kerstin, Juhl, Hartmut, Van Le, Xuan, Kohl, Bernard, Thorp, Richard, Viet Tien, Nguyen, Van Bang, Nguyen, Sussman, Howard, Duc Phu, Bui, Hajek, Richard, Phi Hung, Nguyen, Khan, Khurram Z., Muley, Thomas, Mills Shaw, Kenna R., Sheth, Margi, Yang, Liming, Buetow, Ken, Davidsen, Tanja, Demchok, John A., Eley, Greg, Ferguson, Martin, Dillon, Laura A. L., Schaefer, Carl, Guyer, Mark S., Ozenberger, Bradley A., Palchik, Jacqueline D., Peterson, Jane, Sofia, Heidi J., Thomson, Elizabeth, and Johnson, Bruce E.

Published
2012
Full Text
View/download PDF

33. Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing

Author

Manske, Magnus, Miotto, Olivo, Campino, Susana, Auburn, Sarah, Almagro-Garcia, Jacob, Maslen, Gareth, O’Brien, Jack, Djimde, Abdoulaye, Doumbo, Ogobara, Zongo, Issaka, Ouedraogo, Jean-Bosco, Michon, Pascal, Mueller, Ivo, Siba, Peter, Nzila, Alexis, Borrmann, Steffen, Kiara, Steven M., Marsh, Kevin, Jiang, Hongying, Su, Xin-Zhuan, Amaratunga, Chanaki, Fairhurst, Rick, Socheat, Duong, Nosten, Francois, Imwong, Mallika, White, Nicholas J., Sanders, Mandy, Anastasi, Elisa, Alcock, Dan, Drury, Eleanor, Oyola, Samuel, Quail, Michael A., Turner, Daniel J., Ruano-Rubio, Valentin, Jyothi, Dushyanth, Amenga-Etego, Lucas, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Sutherland, Colin, Roper, Cally, Mangano, Valentina, Modiano, David, Tan, John C., Ferdig, Michael T., Amambua-Ngwa, Alfred, Conway, David J., Takala-Harrison, Shannon, Plowe, Christopher V., Rayner, Julian C., Rockett, Kirk A., Clark, Taane G., Newbold, Chris I., Berriman, Matthew, MacInnis, Bronwyn, and Kwiatkowski, Dominic P.

Published
2012
Full Text
View/download PDF

34. Red blood cell tension protects against severe malaria in the Dantu blood group

Author

Kariuki, Silvia N., primary, Marin-Menendez, Alejandro, additional, Introini, Viola, additional, Ravenhill, Benjamin J., additional, Lin, Yen-Chun, additional, Macharia, Alex, additional, Makale, Johnstone, additional, Tendwa, Metrine, additional, Nyamu, Wilfred, additional, Kotar, Jurij, additional, Carrasquilla, Manuela, additional, Rowe, J. Alexandra, additional, Rockett, Kirk, additional, Kwiatkowski, Dominic, additional, Weekes, Michael P., additional, Cicuta, Pietro, additional, Williams, Thomas N., additional, and Rayner, Julian C., additional

Published
2020
Full Text
View/download PDF

35. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Author

Craddock, Nick, Hurles, Matthew E., Cardin, Niall, Pearson, Richard D., Plagnol, Vincent, Robson, Samuel, Vukcevic, Damjan, Barnes, Chris, Conrad, Donald F., Giannoulatou, Eleni, Holmes, Chris, Marchini, Jonathan L., Stirrups, Kathy, Tobin, Martin D., Wain, Louise V., Yau, Chris, Aerts, Jan, Ahmad, Tariq, Daniel Andrews, T., Arbury, Hazel, Attwood, Anthony, Auton, Adam, Ball, Stephen G., Balmforth, Anthony J., Barrett, Jeffrey C., Barroso, Inês, Barton, Anne, Bennett, Amanda J., Bhaskar, Sanjeev, Blaszczyk, Katarzyna, Bowes, John, Brand, Oliver J., Braund, Peter S., Bredin, Francesca, Breen, Gerome, Brown, Morris J., Bruce, Ian N., Bull, Jaswinder, Burren, Oliver S., Burton, John, Byrnes, Jake, Caesar, Sian, Clee, Chris M., Coffey, Alison J., Connell, John M. C., Cooper, Jason D., Dominiczak, Anna F., Downes, Kate, Drummond, Hazel E., Dudakia, Darshna, Dunham, Andrew, Ebbs, Bernadette, Eccles, Diana, Edkins, Sarah, Edwards, Cathryn, Elliot, Anna, Emery, Paul, Evans, David M., Evans, Gareth, Eyre, Steve, Farmer, Anne, Nicol Ferrier, I., Feuk, Lars, Fitzgerald, Tomas, Flynn, Edward, Forbes, Alistair, Forty, Liz, Franklyn, Jayne A., Freathy, Rachel M., Gibbs, Polly, Gilbert, Paul, Gokumen, Omer, Gordon-Smith, Katherine, Gray, Emma, Green, Elaine, Groves, Chris J., Grozeva, Detelina, Gwilliam, Rhian, Hall, Anita, Hammond, Naomi, Hardy, Matt, Harrison, Pile, Hassanali, Neelam, Hebaishi, Husam, Hines, Sarah, Hinks, Anne, Hitman, Graham A, Hocking, Lynne, Howard, Eleanor, Howard, Philip, Howson, Joanna M. M., Hughes, Debbie, Hunt, Sarah, Isaacs, John D., Jain, Mahim, Jewell, Derek P., Johnson, Toby, Jolley, Jennifer D., Jones, Ian R., Jones, Lisa A., Kirov, George, Langford, Cordelia F., Lango-Allen, Hana, Mark Lathrop, G., Lee, James, Lee, Kate L., Lees, Charlie, Lewis, Kevin, Lindgren, Cecilia M., Maisuria-Armer, Meeta, Maller, Julian, Mansfield, John, Martin, Paul, Massey, Dunecan C. O., McArdle, Wendy L., McGuffin, Peter, McLay, Kirsten E., Mentzer, Alex, Mimmack, Michael L., Morgan, Ann E., Morris, Andrew P., Mowat, Craig, Myers, Simon, Newman, William, Nimmo, Elaine R., O’Donovan, Michael C., Onipinla, Abiodun, Onyiah, Ifejinelo, Ovington, Nigel R., Owen, Michael J., Palin, Kimmo, Parnell, Kirstie, Pernet, David, Perry, John R. B., Phillips, Anne, Pinto, Dalila, Prescott, Natalie J., Prokopenko, Inga, Quail, Michael A., Rafelt, Suzanne, Rayner, Nigel W., Redon, Richard, Reid, David M., Renwick, Anthony, Ring, Susan M., Robertson, Neil, Russell, Ellie, St Clair, David, Sambrook, Jennifer G., Sanderson, Jeremy D., Schuilenburg, Helen, Scott, Carol E., Scott, Richard, Seal, Sheila, Shaw-Hawkins, Sue, Shields, Beverley M., Simmonds, Matthew J., Smyth, Debbie J., Somaskantharajah, Elilan, Spanova, Katarina, Steer, Sophia, Stephens, Jonathan, Stevens, Helen E., Stone, Millicent A., Su, Zhan, Symmons, Deborah P. M., Thompson, John R., Thomson, Wendy, Travers, Mary E., Turnbull, Clare, Valsesia, Armand, Walker, Mark, Walker, Neil M., Wallace, Chris, Warren-Perry, Margaret, Watkins, Nicholas A., Webster, John, Weedon, Michael N., Wilson, Anthony G., Woodburn, Matthew, Wordsworth, Paul B., Young, Allan H., Zeggini, Eleftheria, Carter, Nigel P., Frayling, Timothy M., Lee, Charles, McVean, Gil, Munroe, Patricia B., Palotie, Aarno, Sawcer, Stephen J., Scherer, Stephen W., Strachan, David P., Tyler-Smith, Chris, Brown, Matthew A., Burton, Paul R., Caulfield, Mark J., Compston, Alastair, Farrall, Martin, Gough, Stephen C. L., Hall, Alistair S., Hattersley, Andrew T., Hill, Adrian V. S., Mathew, Christopher G., Pembrey, Marcus, Satsangi, Jack, Stratton, Michael R., Worthington, Jane, Deloukas, Panos, Duncanson, Audrey, Kwiatkowski, Dominic P., McCarthy, Mark I., Ouwehand, Willem H., Parkes, Miles, Rahman, Nazneen, Todd, John A., Samani, Nilesh J., and Donnelly, Peter

Published
2010
Full Text
View/download PDF

36. Genetic diversity of the African malaria vector Anopheles gambiae

Author

Matthew W. Hahn, Alison T. Isaacs, Samantha M. O’Loughlin, Tiago Antao, Austin Burt, Mara K. N. Lawniczak, Dominic P. Kwiatkowski, Christina M. Bergey, Michelle M. Riehle, Giordano Bottà, Boubacar Coulibaly, Martin J. Donnelly, Joao Dinis, Alessandra della Torre, Kirk A. Rockett, Krzysztof Kozak, Andrew D. Kern, Christina Hubbart, Nohal Elissa, Kate Rowlands, Bradley J. White, Eleanor Drury, Rachel Giacomantonio, Craig S. Wilding, Ian J. Wright, Kenneth D. Vernick, Michael C. Fontaine, Diego Ayala, Alistair Miles, Kyanne R. Rohatgi, Daniel Mead, Arlete D. Troco, Philip Bejon, Jim Stalker, Janet Midega, Nicholas J. Harding, Abdoulaye Diabaté, Nora J. Besansky, Henry D. Mawejje, Cinzia Malangone, Daniel R. Schrider, Paul Vauterin, H. Charles J. Godfray, Charles M. Mbogo, Igor V. Sharakhov, Anna E. Jeffreys, Seth Redmond, João Pinto, Dushyanth Jyothi, Chris S Clarkson, Victoria Cornelius, Krzysztof Kluczynski, Carlo Costantini, Lee Hart, Richard D. Pearson, Daniel E. Neafsey, Christa Henrichs, Bronwyn MacInnis, David Weetman, Beniamino Caputo, Ben Jeffery, The Royal Society, Bill & Melinda Gates Foundation, Silicon Valley Community Foundation, Medical Research Council (MRC), Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Groningen Institute for Evolutionary Life Sciences [Groningen] (GELIFES), University of Groningen [Groningen], and Fontaine lab

Subjects
Male, 0106 biological sciences, 0301 basic medicine, Mosquito Control, POSITIVE SELECTION, Anopheles gambiae, FLOW, Genome, Insect, Web application development, Guinea-Bissau, 01 natural sciences, Genome, Partner working group, Gene flow, Insecticide Resistance, Kenya, Effective population size, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RA0421, Gabon, Sequencing and data production, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, biology, Uganda, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], INTROGRESSION, genomics, malaria, anopheles gambiae, Anopheles, Project coordination, Crosses, 3. Good health, MOSQUITO, Multidisciplinary Sciences, Mosquito control, QR180, Science & Technology - Other Topics, Female, Burkina Faso, Sample collections—Angola, Gene Flow, X Chromosome, General Science & Technology, Data analysis group, Mosquito Vectors, Polymorphism, Single Nucleotide, 010603 evolutionary biology, Article, QH301, 03 medical and health sciences, CULICIDAE, Cameroon, parasitic diseases, DIVERGENCE, Animals, Anopheles gambiae 1000 Genomes Consortium, POPULATION-STRUCTURE, INCIPIENT SPECIATION, Population Density, Genetic diversity, Science & Technology, Gene Drive Technology, Genetic Variation, Guinea, biology.organism_classification, Malaria, 030104 developmental biology, Evolutionary biology, DROSOPHILA-MELANOGASTER, Africa, Threatened species, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, RESISTANCE
Abstract

The sustainability of malaria control in Africa is threatened by the rise of insecticide resistance in Anopheles mosquitoes, which transmit the disease(1). To gain a deeper understanding of how mosquito populations are evolving, here we sequenced the genomes of 765 specimens of Anopheles gambiae and Anopheles coluzzii sampled from 15 locations across Africa, and identified over 50 million single nucleotide polymorphisms within the accessible genome. These data revealed complex population structure and patterns of gene flow, with evidence of ancient expansions, recent bottlenecks, and local variation in effective population size. Strong signals of recent selection were observed in insecticide-resistance genes, with several sweeps spreading over large geographical distances and between species. The design of new tools for mosquito control using gene-drive systems will need to take account of high levels of genetic diversity in natural mosquito populations.

Published
2017
Full Text
View/download PDF

37. Arctic Ocean annual high in pCO2could shift from winter to summer

Author

Orr, James C., Kwiatkowski, Lester, and Pörtner, Hans-Otto

Abstract

Long-term stress on marine organisms from ocean acidification will differ between seasons. As atmospheric carbon dioxide (CO2) increases, so do seasonal variations of ocean CO2partial pressure (pCO2), causing summer and winter long-term trends to diverge1–5. Trends may be further influenced by an unexplored factor—changes in the seasonal timing of pCO2. In Arctic Ocean surface waters, the observed timing is typified by a winter high and summer low6because biological effects dominate thermal effects. Here we show that 27 Earth system models simulate similar timing under historical forcing but generally project that the summer low, relative to the annual mean, eventually becomes a high across much of the Arctic Ocean under mid-to-high-level CO2emissions scenarios. Often the greater increase in summer pCO2, although gradual, abruptly inverses the chronological order of the annual high and low, a phenomenon not previously seen in climate-related variables. The main cause is the large summer sea surface warming7from earlier retreat of seasonal sea ice8. Warming and changes in other drivers enhance this century’s increase in extreme summer pCO2by 29 ± 9 per cent compared with no change in driver seasonalities. Thus the timing change worsens summer ocean acidification, which in turn may lower the tolerance of endemic marine organisms to increasing summer temperatures.

Published
2022
Full Text
View/download PDF

38. Emergent constraint on Arctic Ocean acidification in the twenty-first century

Author

Jens Terhaar, Laurent Bopp, Lester Kwiatkowski, Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-École des Ponts ParisTech (ENPC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Climate and Environmental Physics [Bern] (CEP), Physikalisches Institut [Bern], Universität Bern [Bern] (UNIBE)-Universität Bern [Bern] (UNIBE), Oeschger Centre for Climate Change Research (OCCR), University of Bern, Nucleus for European Modeling of the Ocean (NEMO R&D ), Laboratoire d'Océanographie et du Climat : Expérimentations et Approches Numériques (LOCEAN), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ANR-18-ERC2-0001,CONVINCE,Contraindre la réponse de la biogéochimie marine au changement climatique(2018), European Project: 643052,H2020,H2020-MSCA-ITN-2014,C-CASCADES(2015), European Project: 234344,EC:FP7:TPT,FP7-AAT-2008-RTD-1,CRESCENDO(2009), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Universität Bern [Bern]-Universität Bern [Bern], Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut de Recherche pour le Développement (IRD)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut de Recherche pour le Développement (IRD)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)

Subjects
0106 biological sciences, Biogeochemical cycle, Aquatic Organisms, 010504 meteorology & atmospheric sciences, Mesopelagic zone, Oceans and Seas, Climate change, [PHYS.PHYS.PHYS-GEO-PH]Physics [physics]/Physics [physics]/Geophysics [physics.geo-ph], engineering.material, 01 natural sciences, History, 21st Century, Calcium Carbonate, Animals, Ecosystem, Marine ecosystem, Human Activities, Seawater, 14. Life underwater, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Multidisciplinary, Arctic Regions, 010604 marine biology & hydrobiology, Aragonite, Ocean acidification, Carbon Dioxide, Hydrogen-Ion Concentration, Carbon, Oceanography, Arctic, 13. Climate action, engineering, Environmental science
Abstract

The ongoing uptake of anthropogenic carbon by the ocean leads to ocean acidification, a process that results in a reduction in pH and in the saturation state of biogenic calcium carbonate minerals aragonite (Ωarag) and calcite (Ωcalc)1,2. Because of its naturally low Ωarag and Ωcalc (refs. 2,3), the Arctic Ocean is considered the region most susceptible to future acidification and associated ecosystem impacts4-7. However, the magnitude of projected twenty-first century acidification differs strongly across Earth system models8. Here we identify an emergent multi-model relationship between the simulated present-day density of Arctic Ocean surface waters, used as a proxy for Arctic deep-water formation, and projections of the anthropogenic carbon inventory and coincident acidification. By applying observations of sea surface density, we constrain the end of twenty-first century Arctic Ocean anthropogenic carbon inventory to 9.0 ± 1.6 petagrams of carbon and the basin-averaged Ωarag and Ωcalc to 0.76 ± 0.06 and 1.19 ± 0.09, respectively, under the high-emissions Representative Concentration Pathway 8.5 climate scenario. Our results indicate greater regional anthropogenic carbon storage and ocean acidification than previously projected3,8 and increase the probability that large parts of the mesopelagic Arctic Ocean will be undersaturated with respect to calcite by the end of the century. This increased rate of Arctic Ocean acidification, combined with rapidly changing physical and biogeochemical Arctic conditions9-11, is likely to exacerbate the impact of climate change on vulnerable Arctic marine ecosystems.

Published
2019
Full Text
View/download PDF

39. LKB1 modulates lung cancer differentiation and metastasis

Author

Ji, Hongbin, Ramsey, Matthew R., Hayes, D. Neil, Fan, Cheng, McNamara, Kate, Kozlowski, Piotr, Torrice, Chad, Wu, Michael C., Shimamura, Takeshi, Perera, Samanthi A., Liang, Mei-Chih, Cai, Dongpo, Naumov, George N., Bao, Lei, Contreras, Cristina M., Li, Danan, Chen, Liang, Krishnamurthy, Janakiraman, Koivunen, Jussi, Chirieac, Lucian R., Padera, Robert F., Bronson, Roderick T., Lindeman, Neal I., Christiani, David C., Lin, Xihong, Shapiro, Geoffrey I., Jänne, Pasi A., Johnson, Bruce E., Meyerson, Matthew, Kwiatkowski, David J., Castrillon, Diego H., Bardeesy, Nabeel, Sharpless, Norman E., and Wong, Kwok-Kin

Published
2007
Full Text
View/download PDF

40. Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria

Author

Ruwende, C., Khoo, S.C., Snow, R.W., Yates, S.N.R., Kwiatkowski, D., Gupta, S., Warn, P., Allsopp, C.E.M., Gilbert, S.C., Peschu, N., Newbold, C.I., Greenwood, B.M., Marsh, K., and Hill, A.V.S.

Subjects
Natural immunity -- Genetic aspects, Dehydrogenases -- Health aspects, Deficiency diseases -- Health aspects, Malaria -- Prevention, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Glucose-6-phosphate dehydrogenase deficiency A-(G6PD A-), common in Africa, is found to be related to a 46%-58% risk-reduction of severe malaria for female heterozygotes and male hemiozygotes in two case-control studies of 2,000 African children. A mathematical model measuring the benefits of G6PD A- as protection from severe malaria establishes that it should take only 2,000 to 3,000 years to eradicate malaria since both males and females with G6PD A- are protected and so would be selected by evolution. The current rate of G6PD A-, 50%, would indicate a counterbalancing evolutionary disadvantage that prevented malaria eradication.

Published
1995

41. Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria

Author

McGuire, William, Hill, Adrian V.S., Allsopp, Catherine E.M., Greenwood, Brian M., and Kwiatkowski, Dominic

Subjects
Gambia -- Health aspects, Malaria -- Research, Genetic polymorphisms -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A large case-control study of Gambian children reveals that homozygotes for the TNF2 allele, a variation in the TNF-alpha gene promoter region, are associated with death or chronic neurological sequelae due to cerebral malaria. The disease association characteristic of the TNF2 allele is independent of HLA class I and class II variation, and indicates that modulatory cytokine gene polymorphisms influence the consequence of chronic infection. However, a biological advantage in homozygotes counters the manifestation of elevated risk of cerebral malaria.

Published
1994

42. Detecting recent positive selection in the human genome from haplotype structure

Author

Sabeti, Pardis C., Reich, David E., Higgins, John M., Levine, Haninah Z. P., Richter, Daniel J., Schaffner, Stephen F., Gabriel, Stacey B., Platko, Jill V., Patterson, Nick J., McDonald, Gavin J., Ackerman, Hans C., Campbell, Sarah J., Altshuler, David, Cooper, Richard, Kwiatkowski, Dominic, Ward, Ryk, and Lander, Eric S.

Published
2002

43. Population genetics: Malaria susceptibility and CD36 mutation

Author

Aitman, Timothy J., Cooper, Lisa D., Norsworthy, Penny J., Wahid, Faisal N., Gray, Jennefer K., Curtis, Brian R., McKeigue, Paul M., Kwiatkowski, Dominic, Greenwood, Brian M., Snow, Robert W., Hill, Adrian V., and Scott, James

Published
2000

44. Common West African HLA antigens are associated with protection from severe malaria

Author

Hill, Adrian V.S., Allsopp, Catherine E.M., Kwiatkowski, Dominic, Anstey, Nicholas M., Twumasi, Patrick, Rowe, Pamela A., Bennett, Stephen, Brewster, David, McMichael, Andrew J., and Greenwood, Brian M.

Subjects
HLA histocompatibility antigens -- Health aspects, Malaria -- Prevention, Africans -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Published
1991

45. Malaria protection due to sickle haemoglobin depends on parasite genotype

Author

Band, Gavin, Leffler, Ellen M., Jallow, Muminatou, Sisay-Joof, Fatoumatta, Ndila, Carolyne M., Macharia, Alexander W., Hubbart, Christina, Jeffreys, Anna E., Rowlands, Kate, Nguyen, Thuy, Gonçalves, Sónia, Ariani, Cristina V., Stalker, Jim, Pearson, Richard D., Amato, Roberto, Drury, Eleanor, Sirugo, Giorgio, d’Alessandro, Umberto, Bojang, Kalifa A., Marsh, Kevin, Peshu, Norbert, Saelens, Joseph W., Diakité, Mahamadou, Taylor, Steve M., Conway, David J., Williams, Thomas N., Rockett, Kirk A., and Kwiatkowski, Dominic P.

Abstract

Host genetic factors can confer resistance against malaria1, raising the question of whether this has led to evolutionary adaptation of parasite populations. Here we searched for association between candidate host and parasite genetic variants in 3,346 Gambian and Kenyan children with severe malaria caused by Plasmodium falciparum. We identified a strong association between sickle haemoglobin (HbS) in the host and three regions of the parasite genome, which is not explained by population structure or other covariates, and which is replicated in additional samples. The HbS-associated alleles include nonsynonymous variants in the gene for the acyl-CoA synthetase family member2–4PfACS8on chromosome 2, in a second region of chromosome 2, and in a region containing structural variation on chromosome 11. The alleles are in strong linkage disequilibrium and have frequencies that covary with the frequency of HbS across populations, in particular being much more common in Africa than other parts of the world. The estimated protective effect of HbS against severe malaria, as determined by comparison of cases with population controls, varies greatly according to the parasite genotype at these three loci. These findings open up a new avenue of enquiry into the biological and epidemiological significance of the HbS-associated polymorphisms in the parasite genome and the evolutionary forces that have led to their high frequency and strong linkage disequilibrium in African P. falciparumpopulations.

Published
2022
Full Text
View/download PDF

46. Genomic reconstruction of the SARS-CoV-2 epidemic in England

Author

Vöhringer, Harald S., Sanderson, Theo, Sinnott, Matthew, De Maio, Nicola, Nguyen, Thuy, Goater, Richard, Schwach, Frank, Harrison, Ian, Hellewell, Joel, Ariani, Cristina V., Gonçalves, Sonia, Jackson, David K., Johnston, Ian, Jung, Alexander W., Saint, Callum, Sillitoe, John, Suciu, Maria, Goldman, Nick, Panovska-Griffiths, Jasmina, Birney, Ewan, Volz, Erik, Funk, Sebastian, Kwiatkowski, Dominic, Chand, Meera, Martincorena, Inigo, Barrett, Jeffrey C., and Gerstung, Moritz

Abstract

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.

Published
2021
Full Text
View/download PDF

47. Signatures of a jet cocoon in early spectra of a supernova associated with a γ-ray burst

Author

Izzo, L., primary, de Ugarte Postigo, A., additional, Maeda, K., additional, Thöne, C. C., additional, Kann, D. A., additional, Della Valle, M., additional, Sagues Carracedo, A., additional, Michałowski, M. J., additional, Schady, P., additional, Schmidl, S., additional, Selsing, J., additional, Starling, R. L. C., additional, Suzuki, A., additional, Bensch, K., additional, Bolmer, J., additional, Campana, S., additional, Cano, Z., additional, Covino, S., additional, Fynbo, J. P. U., additional, Hartmann, D. H., additional, Heintz, K. E., additional, Hjorth, J., additional, Japelj, J., additional, Kamiński, K., additional, Kaper, L., additional, Kouveliotou, C., additional, Krużyński, M., additional, Kwiatkowski, T., additional, Leloudas, G., additional, Levan, A. J., additional, Malesani, D. B., additional, Michałowski, T., additional, Piranomonte, S., additional, Pugliese, G., additional, Rossi, A., additional, Sánchez-Ramírez, R., additional, Schulze, S., additional, Steeghs, D., additional, Tanvir, N. R., additional, Ulaczyk, K., additional, Vergani, S. D., additional, and Wiersema, K., additional

Published
2019
Full Text
View/download PDF

48. Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England

Author

Volz, Erik, Mishra, Swapnil, Chand, Meera, Barrett, Jeffrey C., Johnson, Robert, Geidelberg, Lily, Hinsley, Wes R., Laydon, Daniel J., Dabrera, Gavin, O’Toole, Áine, Amato, Robert, Ragonnet-Cronin, Manon, Harrison, Ian, Jackson, Ben, Ariani, Cristina V., Boyd, Olivia, Loman, Nicholas J., McCrone, John T., Gonçalves, Sónia, Jorgensen, David, Myers, Richard, Hill, Verity, Jackson, David K., Gaythorpe, Katy, Groves, Natalie, Sillitoe, John, Kwiatkowski, Dominic P., Flaxman, Seth, Ratmann, Oliver, Bhatt, Samir, Hopkins, Susan, Gandy, Axel, Rambaut, Andrew, and Ferguson, Neil M.

Abstract

The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by Sgene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number.

Published
2021
Full Text
View/download PDF

49. Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

Author

Nejentsev, Sergey, Howson, Joanna M. M., Walker, Neil M., Szeszko, Jeffrey, Field, Sarah F., Stevens, Helen E., Reynolds, Pamela, Hardy, Matthew, King, Erna, Masters, Jennifer, Hulme, John, Maier, Lisa M., Smyth, Deborah, Bailey, Rebecca, Cooper, Jason D., Ribas, Gloria, Campbell, R. Duncan, Clayton, David G., Todd, John A., Burton, Paul R., Cardon, Lon R., Craddock, Nick, Deloukas, Panos, Duncanson, Audrey, Kwiatkowski, Dominic P., McCarthy, Mark I., Ouwehand, Willem H., Samani, Nilesh J., Donnelly, Peter, Barrett, Jeffrey C., Davison, Dan, Easton, Doug, Evans, David, Leung, Hin-Tak, Marchini, Jonathan L., Morris, Andrew P., Spencer, Chris C. A., Tobin, Martin D., Attwood, Antony P., Boorman, James P., Cant, Barbara, Everson, Ursula, Hussey, Judith M., Jolley, Jennifer D., Knight, Alexandra S., Koch, Kerstin, Meech, Elizabeth, Nutland, Sarah, Prowse, Christopher V., Taylor, Niall C., Walters, Graham R., Watkins, Nicholas A., Winzer, Thilo, Jones, Richard W., McArdle, Wendy L., Ring, Susan M., Strachan, David P., Pembrey, Marcus, Breen, Gerome, St Clair, David, Caesar, Sian, Gordon-Smith, Katherine, Jones, Lisa, Fraser, Christine, Green, Elaine K., Grozeva, Detelina, Hamshere, Marian L., Holmans, Peter A., Jones, Ian R., Kirov, George, Moskvina, Valentina, Nikolov, Ivan, O'Donovan, Michael C., Owen, Michael J., Collier, David A., Elkin, Amanda, Farmer, Anne, Williamson, Richard, McGuffin, Peter, Young, Allan H., Nicol Ferrier, I., Ball, Stephen G., Balmforth, Anthony J., Barrett, Jennifer H., Bishop, D. Timothy, Iles, Mark M., Maqbool, Azhar, Yuldasheva, Nadira, Hall, Alistair S., Braund, Peter S., Dixon, Richard J., Mangino, Massimo, Stevens, Suzanne, Thompson, John R., Bredin, Francesca, Tremelling, Mark, Parkes, Miles, Drummond, Hazel, Lees, Charles W., Nimmo, Elaine R., Satsangi, Jack, Fisher, Sheila A., Forbes, Alastair, Lewis, Cathryn M., Onnie, Clive M., Prescott, Natalie J., Sanderson, Jeremy, Mathew, Christopher G., Barbour, Jamie, Khalid Mohiuddin, M., Todhunter, Catherine E., Mansfield, John C., Ahmad, Tariq, Cummings, Fraser R., Jewell, Derek P., Webster, John, Brown, Morris J., Lathrop, G. Mark, Connell, John, Dominiczak, Anna, Braga, Carolina A., Burke, Beverley, Dobson, Richard, Gungadoo, Johannie, Lee, Kate L., Munroe, Patricia B., Newhouse, Stephen J., Onipinla, Abiodun, Wallace, Chris, Xue, Mingzhan, Caulfield, Mark, Farrall, Martin, Barton, Anne, Bruce, Ian N., Donovan, Hannah, Eyre, Steve, Gilbert, Paul D., Hider, Samantha L., Hinks, Anne M., John, Sally L., Potter, Catherine, Silman, Alan J., Symmons, Deborah P. M., Thomson, Wendy, Worthington, Jane, Dunger, David B., Widmer, Barry, Frayling, Timothy M., Freathy, Rachel M., Lango, Hana, Perry, John R. B., Shields, Beverley M., Weedon, Michael N., Hattersley, Andrew T., Hitman, Graham A., Walker, Mark, Elliott, Kate S., Groves, Christopher J., Lindgren, Cecilia M., Rayner, Nigel W., Timpson, Nicholas J., Zeggini, Eleftheria, Newport, Melanie, Sirugo, Giorgio, Lyons, Emily, Vannberg, Fredrik, Hill, Adrian V. S., Bradbury, Linda A., Farrar, Claire, Pointon, Jennifer J., Wordsworth, Paul, Brown, Matthew A., Franklyn, Jayne A., Heward, Joanne M., Simmonds, Matthew J., Gough, Stephen C. L., Seal, Sheila, Stratton, Michael R., Rahman, Nazneen, Ban, Maria, Goris, An, Sawcer, Stephen J., Compston, Alastair, Conway, David, Jallow, Muminatou, Rockett, Kirk A., Bryan, Claire, Bumpstead, Suzannah J., Chaney, Amy, Downes, Kate, Ghori, Jilur, Gwilliam, Rhian, Hunt, Sarah E., Inouye, Michael, Keniry, Andrew, King, Emma, McGinnis, Ralph, Potter, Simon, Ravindrarajah, Rathi, Whittaker, Pamela, Withers, David, Cardin, Niall J., Ferreira, Teresa, Pereira-Gale, Joanne, Hallgrimsdottir, Ingeleif B., Howie, Bryan N., Su, Zhan, Ying Teo, Yik, Vukcevic, Damjan, Bentley, David, and Compston, Alistair

Abstract

Author(s): Sergey Nejentsev [1, 57]; Joanna M. M. Howson (corresponding author) [1, 57]; Neil M. Walker [1]; Jeffrey Szeszko [1]; Sarah F. Field [1]; Helen E. Stevens [1]; Pamela Reynolds [...]

Published
2007
Full Text
View/download PDF

50. Comprehensive molecular profiling of lung adenocarcinoma

Author

Amie Radenbaugh, Noreen Dhalla, Christina Williamson, Charles Saller, James Suh, Ramaswamy Govindan, Travis I. Zack, Paul T. Spellman, Daniel DiCara, Harvey I. Pass, Deepak Srinivasan, William G. Richards, Robert J. Cerfolio, Igor Letovanec, A. Gordon Robertson, Gabriel Sica, Chad J. Creighton, Hendrik Dienemann, Jeffrey A. Borgia, Boris Reva, Bryan F. Meyers, Yiling Lu, Nikolaus Schultz, Christopher I. Amos, Dante Trusty, Carmelo Gaudioso, Michael Meister, James T. Robinson, Lihua Zou, James Shin, Jeremy Parfitt, Darlene Lee, Junyuan Wu, Carl Morrison, Scott L. Carter, Giovanni Ciriello, Nils Weinhold, Elena Nemirovich-Danchenko, Andrew Wei Xu, Christopher G. Maher, Lori Boice, Irina Zaytseva, Dennis A. Wigle, Kenna R. Mills Shaw, Matthew G. Soloway, Matthew Meyerson, Peng Chieh Chen, Frank Schneider, Troy Shelton, Douglas Voet, Steven E. Schumacher, D L Rotin, Saianand Balu, Stuart R. Jefferys, Tom Bodenheimer, Bradley A. Ozenberger, Eric S. Lander, Edward Gabrielson, Konstantin V. Fedosenko, Rehan Akbani, William D. Travis, Ari B. Kahn, Marcin Imielinski, Jacqueline E. Schein, Thomas L. Bauer, Kai Ye, Samuel A. Yousem, Robert C. Onofrio, Thomas Muley, Ayesha S. Bryant, Michael K. Asiedu, Monique Albert, Pei Lin, Corbin D. Jones, Edwina Duhig, Jean C. Zenklusen, Lucinda Fulton, Christina Yau, J. Todd Auman, Leigh B. Thorne, Elena Helman, Richard T. Cheney, William Lee, Patrick K. Kimes, Juok Cho, Alexei Protopopov, Wenbin Liu, Lee Lichtenstein, Jing Wang, Lixing Yang, W. Kimryn Rathmell, Jo Ellen Weaver, David A. Wheeler, Leslie Cope, Mark A. Watson, Heidi J. Sofia, Angeliki Pantazi, Ronglai Shen, Jeffrey Roach, Eric A. Collisson, Patrick Kwok Shing Ng, Angela Hadjipanayis, Peter S. Hammerman, David Van Den Berg, Kwun M. Fong, Nils Gehlenborg, Natasha Rekhtman, William K. Funkhouser, D. Neil Hayes, Harshad S. Mahadeshwar, Semin Lee, Martin Peifer, David Mallery, Piotr A. Mieczkowski, Ranabir Guin, Madhusmita Behera, Philipp A. Schnabel, Jill M. Siegfried, Carmen Gomez-Fernandez, Johanna Gardner, Lynn M. Herbert, Hailei Zhang, Robert S. Fulton, Travis Sullivan, Sahil Seth, Sam Ng, Chandra Sekhar Pedamallu, Barry S. Taylor, Venkatraman E. Seshan, Valerie W. Rusch, Jinze Liu, Daniel P. Raymond, Jianjiong Gao, Nathan A. Pennell, Marco A. Marra, Jan F. Prins, Payal Sipahimalani, Janae V. Simons, Joel S. Parker, Rileen Sinha, Lindy Hunter, Raju Kucherlapati, Dennis T. Maglinte, Fedor Moiseenko, Eric E. Snyder, Roy Tarnuzzer, Beverly Lee, James Stephen Marron, Kristian Cibulskis, Jerome Myers, Haiyan I. Li, Robert Penny, Hartmut Juhl, Richard K. Wilson, Zhining Wang, Eran Hodis, Carrie Sougnez, Jiabin Tang, William Mallard, Bryan Hernandez, Liming Yang, Jennifer Brown, Gad Getz, Farhad Kosari, Catrina Fronick, Juliann Chmielecki, Jianhua Zhang, Suresh S. Ramalingam, Michael Parfenov, Peter J. Park, Tanja Davidsen, Philip H. Lai, Jeff Boyd, Dang Huy Quoc Thinh, Harmanjatinder S. Sekhon, Malcolm V. Brock, Mark Pool, Margi Sheth, Kimberly M. Rieger-Christ, Michael J. Liptay, E. Getz, S. Onur Sumer, Ian A. Yang, B. Arman Aksoy, Douglas B. Flieder, Bradley M. Broom, Carrie Hirst, Solange Peters, Joshua M. Stuart, Khurram Z. Khan, Scott Morris, Donghui Tan, Andrew J. Mungall, Ming-Sound Tsao, Gordon B. Mills, Stephen B. Baylin, Rebecca Carlsen, Sanja Dacic, Julien Baboud, Brenda Rabeno, Richard A. Hajek, Lauren Averett Byers, Yaron S.N. Butterfield, Miruna Balasundaram, Chip Stewart, Katherine Tarvin, Peter B. Illei, James G. Herman, David J. Kwiatkowski, Andy Chu, David Haussler, Natasja Wye, Charles M. Perou, Peter W. Laird, Timothy J. Triche, Yan Shi, Jill P. Mesirov, Angela N. Brooks, Lori Huelsenbeck-Dill, Steven J.M. Jones, Antonia H. Holway, Lixia Diao, Anthony A. Gal, David G. Beer, Angela Tam, Ashley H. Salazar, Mark A. Jensen, Robert A. Holt, Katherine A. Hoadley, John A. Demchok, Sandra McDonald, Chandra Goparaju, David Pot, Belinda E. Clarke, Gordon Robertson, Michael C. Wendl, Helga Thorvaldsdottir, Kristen Rogers, Joshua D. Campbell, Chris Sander, Rayleen V. Bowman, Marc Danie Nazaire, Michael Mayo, Olga Voronina, Ludmila Danilova, Paul Zippile, Netty Santoso, John V. Heymach, Matthew D. Wilkerson, John Eckman, Morgan Windsor, Cureline Oleg Dolzhanskiy, Nina Thiessen, Mara Rosenberg, Gideon Dresdner, Levi A. Garraway, Eric Chuah, Richard Varhol, Elizabeth Buda, Li Ding, Alice H. Berger, Xingzhi Song, John M. S. Bartlett, Michael D. McLellan, Olga Potapova, Joseph Paulauskis, Igor Jurisica, Benjamin Gross, Jaegil Kim, John N. Weinstein, Kevin Lau, Christopher R. Cabanski, Philip Bonomi, Michael S. Noble, Maureen F. Zakowski, George E. Sandusky, Mary Iacocca, Eric J. Burks, Erin Curley, Lynda Chin, Rajiv Dhir, Singer Ma, Sophie C. Egea, Umadevi Veluvolu, Sugy Kodeeswaran, Christopher A. Miller, Moiz S. Bootwalla, Daniel J. Weisenberger, Shaowu Meng, Mei Huang, Elaine R. Mardis, Gordon Saksena, Nicholas J. Petrelli, Yvonne Owusu-Sarpong, Christopher C. Benz, Bernard Kohl, Jingchun Zhu, David I. Heiman, Carol Farver, Scot Waring, Richard A. Moore, Darshan Singh, Andrew D. Cherniack, Rameen Beroukhim, Michael S. Lawrence, Xiaojia Ren, Marc Ladanyi, Stacey Gabriel, Christine Czerwinski, Alan P. Hoyle, Cancer Genome Atlas Research Network, Collisson, E. A., Campbell, J.D., Brooks, A.N., Berger, A.H., Lee, W., Chmielecki, J., Beer, D.G., Cope, L., Creighton, C.J., Danilova, L., Ding, L., Getz, G., Hammerman, P.S., Hayes, D.N., Hernandez, B., Herman, J.G., Heymach, J.V., Jurisica, I., Kucherlapati, R., Kwiatkowski, D., Ladanyi, M., Robertson, G., Schultz, N., Shen, R., Sinha, R., Sougnez, C., Tsao, M.S., Travis, W.D., Weinstein, J.N., Wigle, D.A., Wilkerson, M.D., Chu, A., Cherniack, A.D., Hadjipanayis, A., Rosenberg, M., Weisenberger, D.J., Laird, P.W., Radenbaugh, A., Ma, S., Stuart, J.M., Averett Byers, L., Baylin, S.B., Govindan, R., Meyerson, M., Gabriel, S.B., Cibulskis, K., Kim, J., Stewart, C., Lichtenstein, L., Lander, E.S., Lawrence, M.S., Kandoth, C., Fulton, R., Fulton, L.L., McLellan, M.D., Wilson, R.K., Ye, K., Fronick, C.C., Maher, C.A., Miller, C.A., Wendl, M.C., Cabanski, C., Mardis, E., Wheeler, D., Balasundaram, M., Butterfield, Y.S., Carlsen, R., Chuah, E., Dhalla, N., Guin, R., Hirst, C., Lee, D., Li, H.I., Mayo, M., Moore, R.A., Mungall, A.J., Schein, J.E., Sipahimalani, P., Tam, A., Varhol, R., Robertson, A., Wye, N., Thiessen, N., Holt, R.A., Jones, S.J., Marra, M.A., Imielinski, M., Onofrio, R.C., Hodis, E., Zack, T., Helman, E., Sekhar Pedamallu, C., Mesirov, J., Saksena, G., Schumacher, S.E., Carter, S.L., Garraway, L., Beroukhim, R., Lee, S., Mahadeshwar, H.S., Pantazi, A., Protopopov, A., Ren, X., Seth, S., Song, X., Tang, J., Yang, L., Zhang, J., Chen, P.C., Parfenov, M., Wei Xu, A., Santoso, N., Chin, L., Park, P.J., Hoadley, K.A., Auman, J.T., Meng, S., Shi, Y., Buda, E., Waring, S., Veluvolu, U., Tan, D., Mieczkowski, P.A., Jones, C.D., Simons, J.V., Soloway, M.G., Bodenheimer, T., Jefferys, S.R., Roach, J., Hoyle, A.P., Wu, J., Balu, S., Singh, D., Prins, J.F., Marron, J.S., Parker, J.S., Perou, C.M., Liu, J., Maglinte, D.T., Lai, P.H., Bootwalla, M.S., Van Den Berg, D.J., Triche, T., Cho, J., DiCara, D., Heiman, D., Lin, P., Mallard, W., Voet, D., Zhang, H., Zou, L., Noble, M.S., Gehlenborg, N., Thorvaldsdottir, H., Nazaire, M.D., Robinson, J., Aksoy, B.A., Ciriello, G., Taylor, B.S., Dresdner, G., Gao, J., Gross, B., Seshan, V.E., Reva, B., Sumer, S.O., Weinhold, N., Sander, C., Ng, S., Zhu, J., Benz, C.C., Yau, C., Haussler, D., Spellman, P.T., Kimes, P.K., Broom, B.M., Wang, J., Lu, Y., Kwok Shing Ng, P., Diao, L., Liu, W., Amos, C.I., Akbani, R., Mills, G.B., Curley, E., Paulauskis, J., Lau, K., Morris, S., Shelton, T., Mallery, D., Gardner, J., Penny, R., Saller, C., Tarvin, K., Richards, W.G., Cerfolio, R., Bryant, A., Raymond, D.P., Pennell, N.A., Farver, C., Czerwinski, C., Huelsenbeck-Dill, L., Iacocca, M., Petrelli, N., Rabeno, B., Brown, J., Bauer, T., Dolzhanskiy, O., Potapova, O., Rotin, D., Voronina, O., Nemirovich-Danchenko, E., Fedosenko, K.V., Gal, A., Behera, M., Ramalingam, S.S., Sica, G., Flieder, D., Boyd, J., Weaver, J., Kohl, B., Huy Quoc Thinh, D., Sandusky, G., Juhl, H., Duhig, E., Illei, P., Gabrielson, E., Shin, J., Lee, B., Rodgers, K., Trusty, D., Brock, M.V., Williamson, C., Burks, E., Rieger-Christ, K., Holway, A., Sullivan, T., Asiedu, M.K., Kosari, F., Rekhtman, N., Zakowski, M., Rusch, V.W., Zippile, P., Suh, J., Pass, H., Goparaju, C., Owusu-Sarpong, Y., Bartlett, J.M., Kodeeswaran, S., Parfitt, J., Sekhon, H., Albert, M., Eckman, J., Myers, J.B., Cheney, R., Morrison, C., Gaudioso, C., Borgia, J.A., Bonomi, P., Pool, M., Liptay, M.J., Moiseenko, F., Zaytseva, I., Dienemann, H., Meister, M., Schnabel, P.A., Muley, T.R., Peifer, M., Gomez-Fernandez, C., Herbert, L., Egea, S., Huang, M., Thorne, L.B., Boice, L., Hill Salazar, A., Funkhouser, W.K., Rathmell, W.K., Dhir, R., Yousem, S.A., Dacic, S., Schneider, F., Siegfried, J.M., Hajek, R., Watson, M.A., McDonald, S., Meyers, B., Clarke, B., Yang, I.A., Fong, K.M., Hunter, L., Windsor, M., Bowman, R.V., Peters, S., Letovanec, I., Khan, K.Z., Jensen, M.A., Snyder, E.E., Srinivasan, D., Kahn, A.B., Baboud, J., Pot, D.A., Mills Shaw, K.R., Sheth, M., Davidsen, T., Demchok, J.A., Wang, Z., Tarnuzzer, R., Zenklusen, J.C., Ozenberger, B.A., Sofia, H.J., Massachusetts Institute of Technology. Department of Biology, and Lander, Eric S.

Subjects
Male, Lung Neoplasms, Adenocarcinoma/genetics, Adenocarcinoma/pathology, Cell Cycle Proteins/genetics, Female, Gene Dosage, Gene Expression Regulation, Neoplastic, Genomics, Humans, Lung Neoplasms/genetics, Lung Neoplasms/pathology, Molecular Typing, Mutation/genetics, Oncogenes/genetics, Sex Factors, Transcriptome/genetics, Adenocarcinoma of Lung, Cell Cycle Proteins, Biology, Adenocarcinoma, Exon, Germline mutation, microRNA, Adenocarcinoma of the lung, medicine, Gene, Multidisciplinary, Oncogene, Oncogenes, medicine.disease, MET Exon 14 Skipping Mutation, Molecular biology, 3. Good health, Mutation, Transcriptome
Abstract

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

Published
2013

Catalog

Books, media, physical & digital resources
See catalog results