Institution
Wellcome Trust Sanger Institute
Nonprofit•Cambridge, 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.
Topics: Population, Genome, Gene, Genome-wide association study, Genomics
Papers published on a yearly basis
Papers
More filters
••
Wellcome Trust Sanger Institute1, University of Nottingham2, Katholieke Universiteit Leuven3, King Abdulaziz Medical City4, Harvard University5, Saarland University6, University of Manchester7, Central Manchester University Hospitals NHS Foundation Trust8, Charité9, University of Oxford10, Glenfield Hospital11, London North West Healthcare NHS Trust12, Leipzig University13, University of Cambridge14, Leeds Teaching Hospitals NHS Trust15, University of London16, Dresden University of Technology17, Princess Anne Hospital18, Salisbury NHS Foundation Trust19, University of Southampton20, Western General Hospital21, Hospital for Sick Children22, National Institutes of Health23, St. Michael's GAA, Sligo24, National Guard Health Affairs25, Cambridge University Hospitals NHS Foundation Trust26, Boston Children's Hospital27, Guy's and St Thomas' NHS Foundation Trust28, NHS Blood and Transplant29, John Radcliffe Hospital30, University of Freiburg31, University of Erlangen-Nuremberg32, Newcastle upon Tyne Hospitals NHS Foundation Trust33, Imperial College London34, Newcastle University35, King Saud bin Abdulaziz University for Health Sciences36, Medical Research Council37
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
••
Newcastle University1, University of Cambridge2, European Bioinformatics Institute3, Wellcome Trust Sanger Institute4, University College London5, Ludwig Maximilian University of Munich6, Newcastle upon Tyne Hospitals NHS Foundation Trust7, University College London Hospitals NHS Foundation Trust8, Royal Free Hospital9, UCL Institute of Child Health10, Harvard University11
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
••
University of California, San Francisco1, National Research Council2, Pasteur Institute3, Wellcome Trust Sanger Institute4, University of Texas Health Science Center at Houston5, University of Aberdeen6, University of Illinois at Urbana–Champaign7, University of Würzburg8, Université de Montréal9, McGill University10, Stanford University11, Weizmann Institute of Science12, University of Minnesota13, University of Lausanne14, Columbia University15
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
••
Wellcome Trust Sanger Institute1, Newcastle University2, Ghent University3, University of Cambridge4, Wellcome Trust/Cancer Research UK Gurdon Institute5, University College London6, Francis Crick Institute7, Laboratory of Molecular Biology8, Freeman Hospital9, Cambridge University Hospitals NHS Foundation Trust10
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
••
TL;DR: SF3B1 mutation identifies a distinct MDS subtype that is unlikely to develop detrimental subclonal mutations and is characterized by indolent clinical course and favorable outcome.
323 citations
Authors
Showing all 4058 results
Name | H-index | Papers | Citations |
---|---|---|---|
Nicholas J. Wareham | 212 | 1657 | 204896 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
Panos Deloukas | 162 | 410 | 154018 |
Michael R. Stratton | 161 | 443 | 142586 |
David W. Johnson | 160 | 2714 | 140778 |
Michael John Owen | 160 | 1110 | 135795 |
Naveed Sattar | 155 | 1326 | 116368 |
Robert E. W. Hancock | 152 | 775 | 88481 |
Julian Parkhill | 149 | 759 | 104736 |
Nilesh J. Samani | 149 | 779 | 113545 |
Michael Conlon O'Donovan | 142 | 736 | 118857 |
Jian Yang | 142 | 1818 | 111166 |
Christof Koch | 141 | 712 | 105221 |
Andrew G. Clark | 140 | 823 | 123333 |
Stylianos E. Antonarakis | 138 | 746 | 93605 |