Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19
Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19
Abstract The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression. SummaryFeyaerts et al. demonstrate that an integrated analysis of plasma and single-cell proteomics differentiates COVID-19 severity and reveals severity-specific biological signatures associated with the dysregulation of the JAK/STAT, MAPK/mTOR, and NF-κB immune signaling networks and the mobilization of the renin-angiotensin and hemostasis systems.
Gaudilli¨¨re Brice、Meyerowitz Justin G.、Rumer Kristen K.、Aghaeepour Nima、Boyd Scott D.、Nolan Garry P.、Gillard Joshua、Chen Han、Manohar Monali、Fitzpatrick Jessica、Artandi Maja、Chang Iris、Chinthrajah R. Sharon、Warren Christopher M.、Wittman Rich、Ganio Edward A.、Han Xiaoyuan、Mukherjee Nilanjan、Nadeau Kari C.、Feyaerts Dorien、Ferrer Sergio Iv¨￠n Vald¨|s、Angst Martin S.、Tsai Amy S.、Tsai Eileen S.、Stelzer Ina A.、Pinsky Benjamin A.、H¨|dou Julien、Gaudilli¨¨re Dyani K.、Jiang Sizun、Verdonk Franck、Furman David、Ando Kazuo、Peterson Laura S.、Snow Theo T.、Dhondalay Gopal K.R.、Do Evan、Kelly J. Daniel、McIlwain David R.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine||Department of Biomedical Informatics, Stanford University School of MedicineDepartment of Pathology, Stanford University School of Medicine||Sean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford UniversityDepartment of Pathology, Stanford University School of Medicine||Department of Microbiology and Immunology, Stanford University School of MedicineSection Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences||Radboud Center for Infectious DiseasesDepartment of Pathology, Stanford University School of Medicine||Department of Microbiology and Immunology, Stanford University School of MedicineSean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford UniversitySean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford UniversityDepartment of Primary Care and Population Health, Stanford University School of MedicineSean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford UniversitySean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford University||Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University||Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford UniversitySean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford UniversityDepartment of Primary Care and Population Health, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine||Department of Biomedical Sciences, University of the Pacific, Arthur A. Dugoni School of DentistryDepartment of Pathology, Stanford University School of Medicine||Department of Microbiology and Immunology, Stanford University School of MedicineSean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford University||Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Stanford University||Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford UniversityDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDepartamento de Neurolog¨aa, Instituto Nacional de Ciencias M¨|dicas y Nutrici¨?n Salvador Zubir¨￠nDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDepartment of Pathology, Stanford University School of Medicine||Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDivision of Plastic & Reconstructive Surgery, Department of Surgery, Stanford University School of MedicineDepartment of Pathology, Stanford University School of Medicine||Department of Microbiology and Immunology, Stanford University School of MedicineDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineBuck Artificial Intelligence Platform, the Buck Institute for Research on Aging||Stanford 1000 Immunomes Project, Stanford University School of Medicine||Austral Institute for Applied Artificial Intelligence, Institute for Research in Translational Medicine (IIMT), Universidad Austral, CONICETDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of MedicineDivision of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of MedicineSean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford UniversitySean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford UniversitySean N Parker Center for Allergy and Asthma Research, Stanford University Department of Medicine, Stanford UniversityDepartment of Epidemiology and Biostatistics, UCSF||Institute of Global Health Sciences, UCSF||F.I. Proctor Foundation, UCSFDepartment of Pathology, Stanford University School of Medicine||Department of Microbiology and Immunology, Stanford University School of Medicine
医学研究方法基础医学生物科学研究方法、生物科学研究技术
Gaudilli¨¨re Brice,Meyerowitz Justin G.,Rumer Kristen K.,Aghaeepour Nima,Boyd Scott D.,Nolan Garry P.,Gillard Joshua,Chen Han,Manohar Monali,Fitzpatrick Jessica,Artandi Maja,Chang Iris,Chinthrajah R. Sharon,Warren Christopher M.,Wittman Rich,Ganio Edward A.,Han Xiaoyuan,Mukherjee Nilanjan,Nadeau Kari C.,Feyaerts Dorien,Ferrer Sergio Iv¨￠n Vald¨|s,Angst Martin S.,Tsai Amy S.,Tsai Eileen S.,Stelzer Ina A.,Pinsky Benjamin A.,H¨|dou Julien,Gaudilli¨¨re Dyani K.,Jiang Sizun,Verdonk Franck,Furman David,Ando Kazuo,Peterson Laura S.,Snow Theo T.,Dhondalay Gopal K.R.,Do Evan,Kelly J. Daniel,McIlwain David R..Integrated plasma proteomic and single-cell immune signaling network signatures demarcate mild, moderate, and severe COVID-19[EB/OL].(2025-03-28)[2025-07-16].https://www.biorxiv.org/content/10.1101/2021.02.09.430269.点此复制
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