ArticleNature immunology2020
High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation.
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Article in Nature immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
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- The receptor protein tyrosine phosphatase PTPRK promotes intestinal repair and catalysis-independent tumour suppression.Journal of cell science · 2024Article
- COVID-19: Using high-throughput flow cytometry to dissect clinical heterogeneity.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2023Review
- The International Mouse Phenotyping Consortium: comprehensive knockout phenotyping underpinning the study of human disease.Nucleic acids research · 2023Article
- Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature.Frontiers in immunology · 2023Article
- NDRG1 is induced by antigen-receptor signaling but dispensable for B and T cell self-tolerance.Communications biology · 2022Article
- Super-killer CTLs are generated by single gene deletion of Bach2.European journal of immunology · 2022Article
- Lineage-specific protein repeat expansions and contractions reveal malleable regions of immune genes.Genes and immunity · 2022Article
- GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans.The Journal of experimental medicine · 2022Article
- Normality sensing licenses local T cells for innate-like tissue surveillance.Nature immunology · 2022Article
- Immunity to SARS-CoV-2 induced by infection or vaccination.Journal of internal medicine · 2022Review
- Immune status for monitoring and treatment of bladder cancer.Frontiers in immunology · 2022Review
- "Moonlighting" at the power plant: how mitochondria facilitate serial killing by CD8Signal transduction and targeted therapy · 2021Article
- Intercrypt sentinel macrophages tune antibacterial NF-κB responses in gut epithelial cells via TNF.The Journal of experimental medicine · 2021Article
- Genetic landscape of T cells identifies synthetic lethality for T-ALL.Communications biology · 2021Article
- Oropharyngeal Squamous Cell Carcinoma Treatment in the Era of Immune Checkpoint Inhibitors.Viruses · 2021Review
Corrections and comments
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Authors and funding
58 authors at 11 institutions in 4 countries.
Lucie Abeler-Dörner *Department of Immunobiology, King's College London, London, UK.
Adam G Laing *Department of Immunobiology, King's College London, London, UK.
Anna Lorenc *Department of Immunobiology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-1406-7607
Dmitry S UshakovDepartment of Immunobiology, King's College London, London, UK.
Simon ClareWellcome Sanger Institute, Hinxton, UK.
Anneliese O SpeakWellcome Sanger Institute, Hinxton, UK.ORCID http://orcid.org/0000-0003-4890-4685
Maria A Duque-CorreaWellcome Sanger Institute, Hinxton, UK.
Jacqueline K WhiteWellcome Sanger Institute, Hinxton, UK.
Ramiro Ramirez-SolisWellcome Sanger Institute, Hinxton, UK.
Namita SaranDepartment of Immunobiology, King's College London, London, UK.
Katherine R BullMRC Human Immunology Unit, University of Oxford, Oxford, UK.
Belén MorónSir William Dunn School of Pathology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-4815-7536
Jua IwasakiNational Heart and Lung Institute, Imperial College London, London, UK.
Philippa R BartonCambridge Institute of Medical Research, University of Cambridge, Cambridge, UK.
Susana CaetanoDepartment of Immunobiology, King's College London, London, UK.
Keng I HngDepartment of Immunobiology, King's College London, London, UK.
Emma CambridgeWellcome Sanger Institute, Hinxton, UK.
Simon FormanLydia Becker Institute of Immunology and Inflammation, Wellcome Trust Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Tanya L CrockfordMRC Human Immunology Unit, University of Oxford, Oxford, UK.
Mark GriffithsWellcome Sanger Institute, Hinxton, UK.
Leanne KaneWellcome Sanger Institute, Hinxton, UK.
Katherine HarcourtWellcome Sanger Institute, Hinxton, UK.
Cordelia BrandtWellcome Sanger Institute, Hinxton, UK.
George NotleyWellcome Sanger Institute, Hinxton, UK.
Kolawole O BabalolaEuropean Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK.
Jonathan WarrenEuropean Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK.
Jeremy C MasonEuropean Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK.
Amrutha MeenigaEuropean Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK.
Natasha A KarpData Sciences & Quantitative Biology, Discovery Sciences, R&D Biopharmaceuticals, AstraZeneca, Cambridge, UK.
David MelvinWellcome Sanger Institute, Hinxton, UK.
Eleanor CawthorneMRC Human Immunology Unit, University of Oxford, Oxford, UK.
Brian WeinrickDepartment of Microbiology and Immunology, Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0003-0880-4487
Albina RahimTerry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
Sibyl DrisslerTerry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
Justin MeskasTerry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
Alice YueTerry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
Markus LuxTerry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
George X Song-ZhaoSir William Dunn School of Pathology, University of Oxford, Oxford, UK.
Anna ChanDepartment of Immunobiology, King's College London, London, UK.
Carmen Ballesteros ReviriegoWellcome Sanger Institute, Hinxton, UK.
Johannes AbelerDepartment of Economics, University of Oxford, Oxford, UK.
Heather WilsonWellcome Sanger Institute, Hinxton, UK.
Agnieszka Przemska-KosickaDepartment of Immunobiology, King's College London, London, UK.
Matthew EdmansMRC Human Immunology Unit, University of Oxford, Oxford, UK.
Natasha StrevensWellcome Sanger Institute, Hinxton, UK.
Markus PasztorekDepartment of Immunobiology, King's College London, London, UK.
Terrence F MeehanEuropean Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK.
Fiona PowrieThe Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0003-3312-5929
Ryan BrinkmanTerry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
Gordon DouganWellcome Sanger Institute, Hinxton, UK.
William JacobsDepartment of Microbiology and Immunology, Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
Clare M LloydNational Heart and Lung Institute, Imperial College London, London, UK.ORCID http://orcid.org/0000-0001-8977-6726
Richard J CornallMRC Human Immunology Unit, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-6213-3269
Kevin J MaloyInstitute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, UK.
Richard K GrencisLydia Becker Institute of Immunology and Inflammation, Wellcome Trust Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-7592-0085
Gillian M GriffithsCambridge Institute of Medical Research, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-0434-5842
David J AdamsWellcome Sanger Institute, Hinxton, UK.ORCID http://orcid.org/0000-0001-9490-0306
Adrian C HaydayDepartment of Immunobiology, King's College London, London, UK. adrian.hayday@kcl.ac.uk.ORCID http://orcid.org/0000-0002-9495-5793
Wellcome Sanger Institute · GBKing's College London · GBUniversity of Oxford · GBBC Cancer Agency · CAEuropean Bioinformatics Institute · GBAlbert Einstein College of Medicine · USImperial College London · GBUniversity of Cambridge · GBWellcome Centre for Cell-Matrix Research · GBAstraZeneca (United Kingdom) · GBUniversity of Glasgow · GB
Funding
Mouse Phenotyping Informatics Infrastructure - MP12UM1HG006370 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Pilar Cacheiro Martinez, Helen Elizabeth Parkinson · 2016 to 2026
$20.4MMolecular Genetic Analysis of Mycobacterium TuberculosisR37AI026170 · NIAID · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · PI WILLIAM Robert JACOBS · 2004 to 2026
$7.7MMOLECULAR GENETIC ANALYSIS OF MYCOBACTERIUM TUBERCULOSISR01AI026170 · NIAID · YESHIVA UNIVERSITY · PI JACOBS, WILLIAM ROBERT · 1989 to 2022
$7.1MBig Flow Cytometry Data: Data Standards, Integration and AnalysisR01GM118417 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI FINAK, GREG · 2017 to 2020
$1.2MCancer Research UK 20265Cancer Research UK FC001093Medical Research Council MC_UU_00008/6Medical Research Council MR/R007748/1NHGRI NIH HHS UM1 HG006370NIAID NIH HHS R01 AI026170NIAID NIH HHS R37 AI026170NIGMS NIH HHS R01 GM118417Wellcome Trust 102972Wellcome Trust 107059Wellcome Trust 210661/Z/18/ZWellcome Trust FC001093
Abstract
By developing a high-density murine immunophenotyping platform compatible with high-throughput genetic screening, we have established profound contributions of genetics and structure to immune variation (http://www.immunophenotype.org). Specifically, high-throughput phenotyping of 530 unique mouse gene knockouts identified 140 monogenic 'hits', of which most had no previous immunologic association. Furthermore, hits were collectively enriched in genes for which humans show poor tolerance to loss of function. The immunophenotyping platform also exposed dense correlation networks linking immune parameters with each other and with specific physiologic traits. Such linkages limit freedom of movement for individual immune parameters, thereby imposing genetically regulated 'immunologic structures', the integrity of which was associated with immunocompetence. Hence, we provide an expanded genetic resource and structural perspective for understanding and monitoring immune variation in health and disease.
Indexed as
AnimalsCitrobacterEnterobacteriaceae InfectionsFemaleGenetic VariationHigh-Throughput Screening AssaysHumansImmunophenotypingMaleMiceMice, Inbred C57BLMice, KnockoutModels, AnimalSalmonellaSalmonella Infections
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.