Integrated analysis of multimodal single-cell data

Cell, Journal Year: 2021, Volume and Issue: 184(13), P. 3573 - 3587.e29

Published: May 31, 2021

The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce "weighted-nearest neighbor" analysis, unsupervised framework to learn the relative utility each data type in cell, enabling integrative analysis modalities. We apply our procedure a CITE-seq dataset 211,000 human peripheral blood mononuclear cells (PBMCs) with panels extending 228 antibodies construct reference atlas circulating immune system. Multimodal substantially improves ability resolve cell states, allowing us identify validate previously unreported lymphoid subpopulations. Moreover, demonstrate how leverage this rapidly map new datasets interpret responses vaccination coronavirus disease 2019 (COVID-19). Our approach broadly applicable strategy analyze look beyond transcriptome toward unified definition identity.

Language: Английский

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Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19

Cell, Journal Year: 2020, Volume and Issue: 183(1), P. 158 - 168.e14

Published: Aug. 14, 2020

Language: Английский

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Immunology of COVID-19: Current State of the Science

Immunity, Journal Year: 2020, Volume and Issue: 52(6), P. 910 - 941

Published: May 6, 2020

Language: Английский

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Dictionary learning for integrative, multimodal and scalable single-cell analysis

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(2), P. 293 - 304

Published: May 25, 2023

Language: Английский

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Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment

Cell, Journal Year: 2020, Volume and Issue: 182(6), P. 1419 - 1440.e23

Published: Aug. 5, 2020

Language: Английский

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Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans

Science, Journal Year: 2020, Volume and Issue: 369(6508), P. 1210 - 1220

Published: Aug. 11, 2020

Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of patients, we observed reduced expression leukocyte antigen class DR (HLA-DR) proinflammatory cytokines by myeloid as well impaired mammalian target rapamycin (mTOR) signaling interferon-α (IFN-α) production plasmacytoid dendritic cells. By contrast, detected enhanced plasma levels inflammatory mediators-including EN-RAGE, TNFSF14, oncostatin M-which correlated with severity increased bacterial products plasma. Single-cell transcriptomics revealed lack type I IFNs, HLA-DR COVID-19, transient IFN-stimulated genes. This was consistent bulk PBMC transient, low IFN-α during infection. These results reveal mechanisms potential therapeutic targets for COVID-19.

Language: Английский

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Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19

Journal of Allergy and Clinical Immunology, Journal Year: 2020, Volume and Issue: 146(1), P. 128 - 136.e4

Published: May 18, 2020

Language: Английский

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A dynamic COVID-19 immune signature includes associations with poor prognosis

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(10), P. 1623 - 1635

Published: Aug. 17, 2020

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The includes discrete changes in B myelomonocytic cell composition, profoundly altered T phenotypes, selective cytokine/chemokine upregulation SARS-CoV-2-specific antibodies. Some traits identify links other settings immunoprotection immunopathology; others, including basophil plasmacytoid dendritic depletion, correlate strongly disease severity; while third set traits, triad IP-10, interleukin-10 interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation cohorts, individual within may collectively individually guide treatment options; offer insights into pathogenesis; aid early, risk-based patient stratification that is particularly beneficial phasic diseases such as COVID-19. A common are clinically heterogeneous, sheds light pathogenesis progression disease.

Language: Английский

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SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(11), P. 1327 - 1335

Published: Aug. 24, 2020

Language: Английский

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T cell responses in patients with COVID-19

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 20(9), P. 529 - 536

Published: July 29, 2020

Language: Английский

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