Precise identification of cell states altered in disease using healthy single-cell references DOI Creative Commons
Emma Dann, Ana-Maria Cujba, Amanda J. Oliver

и другие.

Nature Genetics, Год журнала: 2023, Номер 55(11), С. 1998 - 2008

Опубликована: Окт. 12, 2023

Abstract Joint analysis of single-cell genomics data from diseased tissues and a healthy reference can reveal altered cell states. We investigate whether integrated collections individuals (cell atlases) are suitable references for disease-state identification matched control samples needed to minimize false discoveries. demonstrate that using atlas latent space learning followed by differential against controls leads improved disease-associated cells, especially with multiple perturbed types. Additionally, when an is available, reducing sample numbers does not increase discovery rates. Jointly analyzing COVID-19 cohort blood atlas, we improve detection infection-related states linked distinct clinical severities. Similarly, studied disease in pulmonary fibrosis lung characterizing two aberrant basal Our provides guidelines designing studies optimizing use.

Язык: Английский

The technological landscape and applications of single-cell multi-omics DOI Open Access
Alev Baysoy, Zhiliang Bai, Rahul Satija

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 24(10), С. 695 - 713

Опубликована: Июнь 6, 2023

Язык: Английский

Процитировано

478

Applications of multi‐omics analysis in human diseases DOI Creative Commons

Chongyang Chen,

Jing Wang,

Donghui Pan

и другие.

MedComm, Год журнала: 2023, Номер 4(4)

Опубликована: Июль 31, 2023

Multi-omics usually refers to the crossover application of multiple high-throughput screening technologies represented by genomics, transcriptomics, single-cell proteomics and metabolomics, spatial so on, which play a great role in promoting study human diseases. Most current reviews focus on describing development multi-omics technologies, data integration, particular disease; however, few them provide comprehensive systematic introduction multi-omics. This review outlines existing technical categories multi-omics, cautions for experimental design, focuses integrated analysis methods especially approach machine learning deep integration corresponding tools, medical researches (e.g., cancer, neurodegenerative diseases, aging, drug target discovery) as well open-source tools databases, finally, discusses challenges future directions precision medicine. With algorithms, important disease research, also provided detailed introduction. will guidance researchers, who are just entering into research.

Язык: Английский

Процитировано

192

An immunodominant NP105–113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease DOI Creative Commons
Yanchun Peng, Suet Ling Felce,

Danning Dong

и другие.

Nature Immunology, Год журнала: 2021, Номер 23(1), С. 50 - 61

Опубликована: Дек. 1, 2021

Abstract NP 105–113 -B*07:02-specific CD8 + T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis clones and single-cell sequencing were performed concurrently, functional avidity antiviral efficacy assessed using an vitro SARS-CoV-2 infection system, correlated receptor usage, transcriptome signature disease severity (acute n = 77, convalescent 52). demonstrated a beneficial cells COVID-19 progression, linked expansion precursors, high effector function. Broad immune memory pools narrowed postinfection but maintained 6 months after preserved to Victoria strain, as well Alpha, Beta, Gamma Delta variants. Our data show that associate efficacy, pointing inclusion for future vaccine design.

Язык: Английский

Процитировано

158

Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis DOI Creative Commons
Andrew Kwok, Alice Allcock, Ricardo C. Ferreira

и другие.

Nature Immunology, Год журнала: 2023, Номер 24(5), С. 767 - 779

Опубликована: Апрель 24, 2023

Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed neutrophils emergency granulopoiesis drove a maladaptive during sepsis. We generated whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune identified populations immunosuppressive mature immature neutrophils. In co-culture, CD66b+ inhibited proliferation activation CD4+ T cells. Single-cell mapping circulating hematopoietic stem progenitor cells (HSPCs) (29,366 27) indicated altered in patients with These features were enriched patient subset poor outcome specific signature displayed higher frequencies IL1R2+ neutrophils, epigenetic transcriptomic signatures HSPCs STAT3-mediated gene regulation across different infectious etiologies syndromes. Our findings offer potential therapeutic targets opportunities for stratified medicine severe infection.

Язык: Английский

Процитировано

140

T Cell Responses to SARS-CoV-2 DOI
Alessandro Sette, John Sidney, Shane Crotty

и другие.

Annual Review of Immunology, Год журнала: 2023, Номер 41(1), С. 343 - 373

Опубликована: Фев. 8, 2023

A large body of evidence generated in the last two and a half years addresses roles T cells SARS-CoV-2 infection following vaccination. Infection or vaccination induces multi-epitope CD4 CD8 cell responses with polyfunctionality. Early have been associated mild COVID-19 outcomes. In concert animal model data, these results suggest that while antibody are key to prevent infection, may also play valuable reducing disease severity controlling infection. memory after is sustained for at least six months. While neutralizing impacted by variants, most preserved. This review highlights extensive progress made, data knowledge gaps remain, our understanding vaccines.

Язык: Английский

Процитировано

129

The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses DOI Open Access
Sam M. Murray, M. Azim Ansari, John Frater

и другие.

Nature reviews. Immunology, Год журнала: 2022, Номер 23(5), С. 304 - 316

Опубликована: Дек. 20, 2022

Язык: Английский

Процитировано

126

COVID-19 and cellular senescence DOI Open Access
Clemens A. Schmitt, Tamar Tchkonia, Laura J. Niedernhofer

и другие.

Nature reviews. Immunology, Год журнала: 2022, Номер 23(4), С. 251 - 263

Опубликована: Окт. 5, 2022

Язык: Английский

Процитировано

108

Secondary influenza challenge triggers resident memory B cell migration and rapid relocation to boost antibody secretion at infected sites DOI Creative Commons
Andrew J. MacLean, Niamh Richmond, Lada A. Koneva

и другие.

Immunity, Год журнала: 2022, Номер 55(4), С. 718 - 733.e8

Опубликована: Март 28, 2022

Resident memory B (BRM) cells develop and persist in the lungs of influenza-infected mice humans; however, their contribution to recall responses has not been defined. Here, we used two-photon microscopy visualize BRM within influenza -virus immune reinfected mice. Prior re-exposure, were sparsely scattered throughout tissue, displaying limited motility. Within 24 h rechallenge, these increased migratory capacity, localized infected sites, subsequently differentiated into plasma cells. Alveolar macrophages mediated this process, part by inducing expression chemokines CXCL9 CXCL10 from infiltrating inflammatory This led recruitment chemokine receptor CXCR3-expressing regions local antibody concentrations. Our study uncovers spatiotemporal mechanisms that regulate lung cell reactivation demonstrates capacity rapidly deliver antibodies a highly manner sites viral replication.

Язык: Английский

Процитировано

93

Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course DOI Creative Commons
Jonathan Muri, Valentina Cecchinato, Andrea Cavalli

и другие.

Nature Immunology, Год журнала: 2023, Номер 24(4), С. 604 - 611

Опубликована: Март 6, 2023

Abstract Infection with severe acute respiratory syndrome coronavirus 2 associates diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors associated adverse disease 2019 (COVID-19) outcomes. Here we discovered that against specific chemokines were omnipresent post-COVID-19, favorable outcome negatively correlated the development of long COVID at 1 yr post-infection. Chemokine also present in HIV-1 infection autoimmune disorders, but they targeted different compared COVID-19. Monoclonal derived from COVID-19 convalescents bound to chemokine N-loop impaired cell migration. Given role orchestrating trafficking, naturally arising may modulate inflammatory response thus bear therapeutic potential.

Язык: Английский

Процитировано

70

Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications DOI Creative Commons
Lea Dib, Lada A. Koneva, Andreas Edsfeldt

и другие.

Nature Cardiovascular Research, Год журнала: 2023, Номер 2(7), С. 656 - 672

Опубликована: Июнь 26, 2023

Abstract The immune system is integral to cardiovascular health and disease. Targeting inflammation ameliorates adverse outcomes. Atherosclerosis, a major underlying cause of disease, conceptualized as lipid-driven in which macrophages play nonredundant role. However, evidence emerging so far from single-cell atlases suggests dichotomy between lipid-associated inflammatory macrophage states. Here, we present an inclusive reference atlas human intraplaque cell communities. Combining RNA sequencing (scRNA-seq) surgical carotid endarterectomies discovery cohort with bulk RNA-seq immunohistochemistry validation (the Carotid Plaque Imaging Project), reveal the existence PLIN2 hi /TREM1 Toll-like receptor (TLR)-dependent state linked cerebrovascular events. Our study shifts current paradigm by providing biological for pathogenic transition phenotype its targeting new treatment strategy

Язык: Английский

Процитировано

56