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Institution

Wellcome Trust Sanger Institute

NonprofitCambridge, United Kingdom
About: Wellcome Trust Sanger Institute is a nonprofit organization based out in Cambridge, United Kingdom. It is known for research contribution in the topics: Population & Genome. The organization has 4009 authors who have published 9671 publications receiving 1224479 citations.


Papers
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Journal ArticleDOI
Alejandro Sifrim1, Marc-Phillip Hitz1, Anna Wilsdon2, Jeroen Breckpot3, Saeed Al Turki4, Saeed Al Turki5, Saeed Al Turki1, Bernard Thienpont3, Jeremy F. McRae1, Tomas W Fitzgerald1, Tarjinder Singh1, Ganesh J. Swaminathan1, Elena Prigmore1, Diana Rajan1, Hashim Abdul-Khaliq6, Siddharth Banka7, Siddharth Banka8, U.M.M. Bauer, Jamie Bentham, Felix Berger9, Shoumo Bhattacharya10, Frances A. Bu'Lock11, Natalie Canham12, Irina-Gabriela Colgiu1, Catherine Cosgrove10, Helen Cox, Ingo Daehnert13, Allan Daly1, John Danesh1, John Danesh14, Alan Fryer, Marc Gewillig3, Emma Hobson15, Kirstin Hoff, Tessa Homfray16, Anne-Karin Kahlert17, Ami Ketley2, Hans-Heiner Kramer, Katherine Lachlan18, Katherine Lachlan19, Katherine Lachlan20, AK Lampe21, Jacoba Louw3, Ashok Kumar Manickara22, Dorin Manase22, Karen P. McCarthy23, Kay Metcalfe8, Carmel Moore14, Ruth Newbury-Ecob24, Seham Osman Omer25, Willem H. Ouwehand, Soo-Mi Park26, Michael Parker27, Thomas Pickardt, Martin O. Pollard1, Leema Robert28, David J. Roberts29, David J. Roberts30, David J. Roberts14, Jennifer G. Sambrook14, Kerry Setchfield2, Brigitte Stiller31, Christopher Thornborough11, Okan Toka32, Hugh Watkins10, Denise Williams, Michael Wright33, Seema Mital22, Piers E.F. Daubeney34, Bernard Keavney7, Judith A. Goodship35, Riyadh M. Abu-Sulaiman36, Riyadh M. Abu-Sulaiman25, Riyadh M. Abu-Sulaiman4, Sabine Klaassen, Caroline F. Wright1, Helen V. Firth26, Jeffrey C. Barrett1, Koenraad Devriendt3, David R. FitzPatrick37, J. David Brook2, Matthew E. Hurles1 
TL;DR: Exome sequenced 1,891 probands and identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1, finding evidence for distinct genetic architectures underlying the low sibling recurrence risk in S- CHD and NS-CHd.
Abstract: Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.

325 citations

Journal ArticleDOI
TL;DR: In this article, the authors performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19.
Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

324 citations

Journal ArticleDOI
TL;DR: Improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl- CoA and enoyl-CoA carriers, and numerous transporters to assimilate the resulting nutrients.
Abstract: Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations) that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy. We also observed that, compared to other fungi, the protein-coding sequences in the C. albicans genome are especially rich in short sequence repeats. Finally, our improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid degrading enzymes, a variety of secreted catabolic lipases and proteases, and numerous transporters to assimilate the resulting nutrients. The results of these efforts will ensure that the Candida research community has uniform and comprehensive genomic information for medical research as well as for future diagnostic and therapeutic applications.

323 citations

Journal ArticleDOI
21 Feb 2020-Science
TL;DR: The authors' single-cell transcriptome profile of the thymus across the human lifetime and across species provides a high-resolution census of T cell development within the native tissue microenvironment, and identifies novel subpopulations of human thymic fibroblasts and epithelial cells and located them in situ.
Abstract: The thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We used single-cell RNA sequencing to create a cell census of the human thymus across the life span and to reconstruct T cell differentiation trajectories and T cell receptor (TCR) recombination kinetics. Using this approach, we identified and located in situ CD8αα+ T cell populations, thymic fibroblast subtypes, and activated dendritic cell states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and the kinetics of lineage commitment. Taken together, our data provide a comprehensive atlas of the human thymus across the life span with new insights into human T cell development.

323 citations


Authors

Showing all 4058 results

NameH-indexPapersCitations
Nicholas J. Wareham2121657204896
Gonçalo R. Abecasis179595230323
Panos Deloukas162410154018
Michael R. Stratton161443142586
David W. Johnson1602714140778
Michael John Owen1601110135795
Naveed Sattar1551326116368
Robert E. W. Hancock15277588481
Julian Parkhill149759104736
Nilesh J. Samani149779113545
Michael Conlon O'Donovan142736118857
Jian Yang1421818111166
Christof Koch141712105221
Andrew G. Clark140823123333
Stylianos E. Antonarakis13874693605
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202317
202270
2021836
2020810
2019854
2018764