Sökning: WFRF:(Carapito Raphael)
> (2022) >
Identification of d...
Identification of driver genes for critical forms of COVID-19 in a deeply phenotyped young patient cohort
-
- Carapito, Raphael (författare)
- Univ Strasbourg, Transplantex NG,Plateforme GENOMAX, Inst Themat Interdisciplinaire ITI Med Precis Str, Fac Med,UMR S 1109,INSERM,Lab ImmunoRhumatol Mol, F-67085 Strasbourg, France.;Nouvel Hop Civil, Serv Immunol Biol, Pole Biol, Plateau Tech Biol, F-67091 Strasbourg, France.;Federat Hosp Univ FHU OMICARE, Ctr Rech Immunol & Hematol, Federat Med Translat Strasbourg FMTS, F-67085 Strasbourg, France.
-
- Pin, Elisa (författare)
- KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
-
- Nilsson, Peter (författare)
- KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab
-
visa fler...
-
- Chittenden, Thomas W. (författare)
- Genuity Sci, Genuity AI Res Inst, Boston, MA 02114 USA.;Harvard Med Sch, Boston Childrens Hosp, Div Genet & Genom, Boston, MA 02115 USA.
-
- Bahram, Seiamak (författare)
- Univ Strasbourg, Transplantex NG,Plateforme GENOMAX, Inst Themat Interdisciplinaire ITI Med Precis Str, Fac Med,UMR S 1109,INSERM,Lab ImmunoRhumatol Mol, F-67085 Strasbourg, France.;Nouvel Hop Civil, Serv Immunol Biol, Pole Biol, Plateau Tech Biol, F-67091 Strasbourg, France.;Federat Hosp Univ FHU OMICARE, Ctr Rech Immunol & Hematol, Federat Med Translat Strasbourg FMTS, F-67085 Strasbourg, France.
-
visa färre...
-
Univ Strasbourg, Transplantex NG,Plateforme GENOMAX, Inst Themat Interdisciplinaire ITI Med Precis Str, Fac Med,UMR S 1109,INSERM,Lab ImmunoRhumatol Mol, F-67085 Strasbourg, France;Nouvel Hop Civil, Serv Immunol Biol, Pole Biol, Plateau Tech Biol, F-67091 Strasbourg, France.;Federat Hosp Univ FHU OMICARE, Ctr Rech Immunol & Hematol, Federat Med Translat Strasbourg FMTS, F-67085 Strasbourg, France. Affinitets-proteomik (creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2022
- 2022
- Engelska.
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 14:628
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://hal.archives...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- The drivers of critical coronavirus disease 2019 (COVID-19) remain unknown. Given major confounding factors such as age and comorbidities, true mediators of this condition have remained elusive. We used a multi-omics analysis combined with artificial intelligence in a young patient cohort where major comorbidities were excluded at the onset. The cohort included 47 "critical" (in the intensive care unit under mechanical ventilation) and 25 "non-critical" (in a non-critical care ward) patients with COVID-19 and 22 healthy individuals. The analyses included whole-genome sequencing, whole-blood RNA sequencing, plasma and blood mononuclear cell proteomics, cytokine profiling, and high-throughput immunophenotyping. An ensemble of machine learning, deep learning, quantum annealing, and structural causal modeling were used. Patients with critical COVID-19 were characterized by exacerbated inflammation, perturbed lymphoid and myeloid compartments, increased coagulation, and viral cell biology. Among differentially expressed genes, we observed up-regulation of the metalloprotease ADAM9. This gene signature was validated in a second independent cohort of 81 critical and 73 recovered patients with COVID-19 and was further confirmed at the transcriptional and protein level and by proteolytic activity. Ex vivo ADAM9 inhibition decreased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake and replication in human lung epithelial cells. In conclusion, within a young, otherwise healthy, cohort of individuals with COVID-19, we provide the landscape of biological perturbations in vivo where a unique gene signature differentiated critical from non-critical patients. We further identified ADAM9 as a driver of disease severity and a candidate therapeutic target.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas