8 research outputs found
Pan-cancer analysis of whole genomes
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- Wendl M. C. z
- wf Amary
- Whalley
- Wheeler
- wi Futreal
- Wigle
- Wilkerson M. D. v
- Williams
- Wilmott
- Wilson G. W. k
- Wilson R. K. z
- Wintersinger
- Wiznerowicz
- Wolf
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- Woo
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- Wouters
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- Wright A. J. k
- ws Ang
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- xp Benz
- xp Edwards
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- xw McDermott
- xy Visakorpi
- xz Whitaker
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- Y. uz
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- Y. yc
- ya Al-Ahmadie
- Yachida
- Yamaguchi
- Yamaguchi T. N. k
- Yamamoto
- Yamaue
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- Yang
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- Yang
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- Yellapantula
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- z ah
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- Zaikova
- Zapatka
- zd Gershenwald
- Zenklusen
- Zeps
- zf Ghossein
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang
- Zhang H. b
- Zhao
- Zheng
- Zhou
- Zhou
- Zhu
- Zhu
- zi zj
- zm Jayaseelan
- Zou
- Zou
- zt Kim
- zw Lewis
- Ó. A. th
- Ø. sk
- Publication venue
- Publication date
- 11/12/2019
- Field of study
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.
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- Aanensen DM
- Abudahab K
- Adams A
- Adams H
- Adeniji K
- Afifi S
- Aggarwal D
- Agranoff D
- Agwuh K
- Ahmad SSY
- Ahmed KA
- Aigrain L
- Ail D
- Alcolea-Medina A
- Aldera EL
- Alegria A
- Alex B
- Alikhan N-F
- Allara E
- Allen S
- Amato R
- Andrikopoulos P
- Angus B
- Angyal A
- Annett T
- Aplin S
- Ariani CV
- Armstrong JA
- Asad H
- Ash A
- Ashfield P
- Ashford F
- Ashish A
- Ashworth M
- Asiimwe IG
- Atkinson D
- Atkinson L
- Attwood SW
- Auckland C
- Aydin A
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- Baillie JK
- Baker DJ
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- Balcazar CE
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- Bari S
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- Publication venue
- iScience
- Publication date
- 01/01/2021
- Field of study
We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC
O CNJ E Um Possível Novo Pacto Federativo: Reflexos Da Experiência Do Conselho Nacional De Justiça No Federalismo Brasileiro (The CNJ And A Possible New Federative Pact: Reflections From Experience The National Council Of Justice In Brazilian Federalism)
- Author
- Andrei Koener
- Andr� Tavares
- Ant�nio Peleja Junior
- B Da
- Christiane Vieira Pedersoli
- Cl�merson Cl�ve
- E Associa��o
- Francisco Soares Reis
- George Anderson
- Ives Silva
- Joaquim
- Jos� Eduardo Faria
- Jos� Nalini
- Jos� Sampaio
- Luiz Vianna
- Lu�s Barroso
- Lu�s Barroso
- Marco Villa
- Maria Sadek
- Miriam Dolhnikoff
- Nuno
- Paulo Roberto Ramos
- Pierpaolo Bottini
- Pode-Se
- Raymundo Faoro
- Robl Filho
- Rulli Neto
- S�o Paulo
- Thomas Flory
- Victor Leonardi
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2013
- Field of study
Breves Consideraaaes Acerca Dos 'Chillings Effects' (Efeitos Paralisantes) No mbito Discursivo Da Liberdade De Expressso (Brief Remarks About 'Chillings Effects' on the Discursive Role of Freedom of Speech)
- Author
- ______
- ______ Imprensa
- A J Morais
- Agust�n Parise
- Ala�r Caff� Alves
- Almir Oliveira
- Anthony Lewis
- Ant�nio Augusto Trindade
- Arnaldo Godoy
- B�rbara J�lia Leit�o
- Calmom J J De Passos
- Cl�merson Cl�ve
- F B�ez
- Francisco Toledo
- Frederick Schauer
- George Orwell
- Gilberto Freyre
- Gilmar Mendes
- Herrera Flores
- J C Gibson
- Joaqu�n Herrera Flores
- Jorge A Cordero
- Karl Marx
- L R Barroso
- Leslie Kendrick
- Marcelo Neves
- Margarida Knobbe
- Negt
- Pondera��o Crit�rios De
- Prado Junior
- Raymundo Faoro
- Richard
- Rubem A Alves
- S�rgio Holanda
- Thiago Santos Aguiar de PPdua
- Ursula Cheer
- Vamireh Chacon
- Victor Leal
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2014
- Field of study
Do Specialized Courts Make a Difference? Evidence from Brazilian State Supreme Courts
- Author
- Alec Stone Sweet
- Amilton Bueno De Carvalho
- Arnoldo Hely Lopes Meirelles
- B Rogerio
- Bulos Uadi Lamm�go
- Burgos
- Carolina Arlota
- Claudio Pereira De Souza Neto &
- Cl�ve Cl�merson Merlin
- Comella V�ctor Ferreres
- Comella V�ctor Ferreres
- Daniel M Brinks
- Daniel M Brinks
- Daniel M Brinks
- Diana Kapiszewski
- Florencio Rafael La Porta
- Gilmar Ferreira Mendes &
- Giuseppe Dari-Mattiacci
- Hans Kelsen
- Hans Kelsen
- Kenneth L Karst
- M Matthew
- Marcelo Luiz Werneck Vianna
- Marcus Faro De Castro
- Maria Luiz Werneck Vianna
- Martin Shapiro
- Matthew M Taylor
- Matthew M Taylor
- Mauro Cappelletti
- Nuno Garoupa
- Nuno Garoupa
- Nuno M. Garoupa
- Oscar Vilhena Vieira
- Ricardo Ribeiro
- Richard L Revesz
- Richard Posner
- Roberto Lu�s
- Rochelle Cooper
- Rochelle Cooper
- Rodrigo M Nunes
- Tom Ginsburg
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2015
- Field of study
Direitos Sociais, Estado De Direito E Desigualdade: Reflexxes Sobre as Crrticas Judicializaaao Dos Direitos Prestacionais (Social Rights, Rule of Law and Inequality: Reflections on the critical reviews about judicialization of positive rights)
- Author
- Alexandre Freire
- Aline Matias Costa
- Alonso Freire
- Amy
- Anashri Pillay
- Andreas J Krell
- Barry Friedman
- C Tate
- Cass R Sunstein
- Celso Mello
- Cl�merson Cl�ve
- Cristina Queiroz
- C�cile Fabre
- D M Davis
- Daniel ( Sarmento
- Daniel ( Sarmento
- Daniel Sarmento
- Daniel Sarmento
- Daniel Sarmento
- Daniel Sarmento
- David Horowitz
- Dieter Grimm
- Fl�via Piovesan
- Fl�vio Galdino
- Francisco J Pel�ez
- Frank Habermas
- Frank I Michelman
- Gabriel Gon�alves
- Gilmar Mendes
- Gilmar Mendes
- Gregorio Mart�nez
- Gustavo Amaral
- Ingo Sarlet
- Jacques Fierens
- Jane Reis Gonnalves Pereira
- Jane Reis Pereira
- Jeff King
- Jeremy Waldron
- John Rawls
- Jorge Novais
- Joseph E Potter
- Josh Blackman
- Jos� A��n
- Jos� Carvalho
- Jos� Merquior
- Jo�o Espada
- Junqueiro Caetano
- Katharine G Young
- Lenio Streck
- Lenio Streck
- Leonardo ( Martins
- Leopoldo
- Lon Fuller
- Luis Roniger
- Lu�s Barroso
- Malcolm Langford
- Marcelo Neves
- Marcus Orione Correia
- Mark Tushnet
- Mart�n Borowski
- Matthias
- Minist�rio Da Sa�de
- Miriam Silva
- Oscar Vieira
- Paulo Bonavides
- Paulo Gilberto Leivas
- Paulo Gustavo Branco
- Ran Hirschl
- Refer�ncias Bibliogr�ficas
- Ricardo Torres
- Robert Alexy
- Roberto Gargarella
- Rodolfo
- Siddharta Ferreira
- Simeon Nichter
- Souza
- Stephen _____Holmes
- Sujit Choudhry
- T H Marshall
- Vicente Faleiros
- Virg�lio Afonso Silva
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2015
- Field of study
Mapping the human genetic architecture of COVID-19
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- Abdelrazik M
- Abdullah T
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- Abecasis GR
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- Uchimura Y
- Uddin MJ
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- Ueda S
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- Uellendahl-Werth F
- Uffelmann E
- Umeda A
- Underwood SJ
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- Ustianowski A
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- Uwamino Y
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- Valentine J
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- van Heel D
- van Heel DA
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- van Mourik N
- Van Singer M
- van Tonder L
- van Uffelen KWJ
- van Vugt M
- Vandernoot I
- Varghese M
- Vari MS
- Varnai R
- Vecchia M
- Vedage D
- Veelo D
- Veerapen K
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- Veerapen K
- Vehreschild MJGT
- Velho M
- Venkatesh H
- Venturelli S
- Verdugo RA
- Vergori A
- Verlander M
- Verma A
- Verma SS
- Vertue M
- Vertue M
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- Vitart V
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- Vlaar APJ
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- Voide C
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- Vollenweider P
- Von Frenckell C
- von Hohenstaufen K
- von Mering C
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- Vuylsteke A
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- Wackett T
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- Waddy S
- Wagstaff V
- Waite AAC
- Wakabayashi A
- Wakahara K
- Wake R
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- Wakinshaw F
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- Wang Q
- Wang X
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- Watanabe K
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- Wooton DG
- Working UCLAHATLASDM
- Workman A
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- Wyllie DH
- Wynter I
- Xavier K
- Xue X
- Yadav A
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- Yamada M
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- Yasui Y
- Yates B
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- Ye C
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- Yi X
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- Yoon H
- Yoon KJ
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- Yoshihara T
- Yoshiya K
- Yoshiyama T
- Youlton N
- Younes SE
- Young P
- Yun N
- Zak A
- Zaki A
- Zambon M
- Zamikula J
- Zanella A
- Zanella I
- Zanelli G
- Zara F
- Zara F
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- Zborowski AC
- Zeberg H
- Zechner M
- Zechner M
- Zguro K
- Zhai R
- Zhang JE
- Zhang M
- Zhao JH
- Zhen J
- Zheng C
- Zheng T
- Zhou W
- Zhou W
- Zhu W
- Zitter L
- Zlatopolsky M
- Zoller H
- Zollner S
- Zongo O
- zu Bentrup FM
- Zucchi P
- Zwinderman AHK
- Zyndorf M
- Publication venue
- Publication date
- 01/01/2021
- Field of study
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease