001     178091
005     20211215112321.0
024 7 _ |a 10.1186/s13073-020-00823-5
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024 7 _ |a pmc:PMC7805430
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037 _ _ |a DKFZ-2021-03098
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Aschenbrenner, Anna C
|b 0
245 _ _ |a Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.
260 _ _ |a London
|c 2021
|b BioMed Central
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
|b journal
|m journal
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system.In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings.Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo01.inet.dkfz-heidelberg.de
650 _ 7 |a Blood transcriptomics
|2 Other
650 _ 7 |a COVID-19
|2 Other
650 _ 7 |a Co-expression analysis
|2 Other
650 _ 7 |a Drug repurposing
|2 Other
650 _ 7 |a Granulocytes
|2 Other
650 _ 7 |a Molecular disease phenotypes
|2 Other
650 _ 7 |a Neutrophils
|2 Other
650 _ 7 |a Stratification
|2 Other
650 _ 7 |a Transcriptome
|2 Other
650 _ 7 |a Antiviral Agents
|2 NLM Chemicals
650 _ 7 |a RNA
|0 63231-63-0
|2 NLM Chemicals
650 _ 2 |a Antiviral Agents: therapeutic use
|2 MeSH
650 _ 2 |a COVID-19: drug therapy
|2 MeSH
650 _ 2 |a COVID-19: pathology
|2 MeSH
650 _ 2 |a COVID-19: virology
|2 MeSH
650 _ 2 |a Case-Control Studies
|2 MeSH
650 _ 2 |a Down-Regulation
|2 MeSH
650 _ 2 |a Drug Repositioning
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Neutrophils: cytology
|2 MeSH
650 _ 2 |a Neutrophils: immunology
|2 MeSH
650 _ 2 |a Neutrophils: metabolism
|2 MeSH
650 _ 2 |a Phenotype
|2 MeSH
650 _ 2 |a Principal Component Analysis
|2 MeSH
650 _ 2 |a RNA: blood
|2 MeSH
650 _ 2 |a RNA: chemistry
|2 MeSH
650 _ 2 |a RNA: metabolism
|2 MeSH
650 _ 2 |a Sequence Analysis, RNA
|2 MeSH
650 _ 2 |a Severity of Illness Index
|2 MeSH
650 _ 2 |a Transcriptome
|2 MeSH
650 _ 2 |a Up-Regulation
|2 MeSH
700 1 _ |a Mouktaroudi, Maria
|b 1
700 1 _ |a Krämer, Benjamin
|b 2
700 1 _ |a Oestreich, Marie
|b 3
700 1 _ |a Antonakos, Nikolaos
|b 4
700 1 _ |a Nuesch-Germano, Melanie
|b 5
700 1 _ |a Gkizeli, Konstantina
|b 6
700 1 _ |a Bonaguro, Lorenzo
|b 7
700 1 _ |a Reusch, Nico
|b 8
700 1 _ |a Baßler, Kevin
|b 9
700 1 _ |a Saridaki, Maria
|b 10
700 1 _ |a Knoll, Rainer
|b 11
700 1 _ |a Pecht, Tal
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700 1 _ |a Kapellos, Theodore S
|b 13
700 1 _ |a Doulou, Sarandia
|b 14
700 1 _ |a Kröger, Charlotte
|b 15
700 1 _ |a Herbert, Miriam
|b 16
700 1 _ |a Holsten, Lisa
|b 17
700 1 _ |a Horne, Arik
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700 1 _ |a Gemünd, Ioanna D
|b 19
700 1 _ |a Rovina, Nikoletta
|b 20
700 1 _ |a Agrawal, Shobhit
|b 21
700 1 _ |a Dahm, Kilian
|b 22
700 1 _ |a van Uelft, Martina
|b 23
700 1 _ |a Drews, Anna
|b 24
700 1 _ |a Lenkeit, Lena
|b 25
700 1 _ |a Bruse, Niklas
|b 26
700 1 _ |a Gerretsen, Jelle
|b 27
700 1 _ |a Gierlich, Jannik
|b 28
700 1 _ |a Becker, Matthias
|b 29
700 1 _ |a Händler, Kristian
|b 30
700 1 _ |a Kraut, Michael
|b 31
700 1 _ |a Theis, Heidi
|b 32
700 1 _ |a Mengiste, Simachew
|b 33
700 1 _ |a De Domenico, Elena
|b 34
700 1 _ |a Schulte-Schrepping, Jonas
|b 35
700 1 _ |a Seep, Lea
|b 36
700 1 _ |a Raabe, Jan
|b 37
700 1 _ |a Hoffmeister, Christoph
|b 38
700 1 _ |a ToVinh, Michael
|b 39
700 1 _ |a Keitel, Verena
|b 40
700 1 _ |a Rieke, Gereon
|b 41
700 1 _ |a Talevi, Valentina
|b 42
700 1 _ |a Skowasch, Dirk
|b 43
700 1 _ |a Aziz, N Ahmad
|b 44
700 1 _ |a Pickkers, Peter
|b 45
700 1 _ |a van de Veerdonk, Frank L
|b 46
700 1 _ |a Netea, Mihai G
|b 47
700 1 _ |a Schultze, Joachim L
|b 48
700 1 _ |a Kox, Matthijs
|b 49
700 1 _ |a Breteler, Monique M B
|b 50
700 1 _ |a Nattermann, Jacob
|b 51
700 1 _ |a Koutsoukou, Antonia
|b 52
700 1 _ |a Giamarellos-Bourboulis, Evangelos J
|b 53
700 1 _ |a Ulas, Thomas
|0 0000-0002-9785-4197
|b 54
700 1 _ |a Initiative, German COVID-19 Omics
|b 55
|e Collaboration Author
700 1 _ |a Altmüller, Janine
|b 56
700 1 _ |a Angelov, Angel
|b 57
700 1 _ |a Bals, Robert
|b 58
700 1 _ |a Bartholomäus, Alexander
|b 59
700 1 _ |a Becker, Anke
|b 60
700 1 _ |a Bitzer, Michael
|b 61
700 1 _ |a Bonifacio, Ezio
|b 62
700 1 _ |a Bork, Peer
|b 63
700 1 _ |a Casadei, Nicolas
|b 64
700 1 _ |a Clavel, Thomas
|b 65
700 1 _ |a Colome-Tatche, Maria
|b 66
700 1 _ |a Diefenbach, Andreas
|b 67
700 1 _ |a Dilthey, Alexander
|b 68
700 1 _ |a Fischer, Nicole
|b 69
700 1 _ |a Förstner, Konrad
|b 70
700 1 _ |a Franzenburg, Sören
|b 71
700 1 _ |a Frick, Julia-Stefanie
|b 72
700 1 _ |a Gabernet, Gisela
|b 73
700 1 _ |a Gagneur, Julien
|b 74
700 1 _ |a Ganzenmüller, Tina
|b 75
700 1 _ |a Göpel, Siri
|b 76
700 1 _ |a Goesmann, Alexander
|b 77
700 1 _ |a Hain, Torsten
|b 78
700 1 _ |a Heimbach, André
|b 79
700 1 _ |a Hummel, Michael
|b 80
700 1 _ |a Iftner, Angelika
|b 81
700 1 _ |a Iftner, Thomas
|b 82
700 1 _ |a Janssen, Stefan
|b 83
700 1 _ |a Kalinowski, Jörn
|b 84
700 1 _ |a Kallies, René
|b 85
700 1 _ |a Kehr, Birte
|b 86
700 1 _ |a Keller, Andreas
|b 87
700 1 _ |a Kim-Hellmuth, Sarah
|b 88
700 1 _ |a Klein, Christoph
|b 89
700 1 _ |a Kohlbacher, Oliver
|b 90
700 1 _ |a Köhrer, Karl
|b 91
700 1 _ |a Korbel, Jan
|b 92
700 1 _ |a Kühnert, Denise
|b 93
700 1 _ |a Kurth, Ingo
|b 94
700 1 _ |a Landthaler, Markus
|b 95
700 1 _ |a Li, Yang
|b 96
700 1 _ |a Ludwig, Kerstin
|b 97
700 1 _ |a Makarewicz, Oliwia
|b 98
700 1 _ |a Marz, Manja
|b 99
700 1 _ |a McHardy, Alice
|b 100
700 1 _ |a Mertes, Christian
|b 101
700 1 _ |a Nöthen, Markus
|b 102
700 1 _ |a Nürnberg, Peter
|b 103
700 1 _ |a Ohler, Uwe
|b 104
700 1 _ |a Ossowski, Stephan
|b 105
700 1 _ |a Overmann, Jörg
|b 106
700 1 _ |a Pfeffer, Klaus
|b 107
700 1 _ |a Poetsch, Anna R
|b 108
700 1 _ |a Pühler, Alfred
|b 109
700 1 _ |a Rajewsky, Nikolaus
|b 110
700 1 _ |a Ralser, Markus
|b 111
700 1 _ |a Rieß, Olaf
|b 112
700 1 _ |a Ripke, Stephan
|b 113
700 1 _ |a Nunes da Rocha, Ulisses
|b 114
700 1 _ |a Rosenstiel, Philip
|b 115
700 1 _ |a Saliba, Antoine-Emmanuel
|b 116
700 1 _ |a Sander, Leif Erik
|b 117
700 1 _ |a Sawitzki, Birgit
|b 118
700 1 _ |a Schiffer, Philipp
|b 119
700 1 _ |a Schneider, Wulf
|b 120
700 1 _ |a Schulte, Eva-Christina
|b 121
700 1 _ |a Schultze, Joachim L
|b 122
700 1 _ |a Sczyrba, Alexander
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700 1 _ |a Singh, Yogesh
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700 1 _ |a Sonnabend, Michael
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700 1 _ |a Stegle, Oliver
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700 1 _ |a Stoye, Jens
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700 1 _ |a Theis, Fabian
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700 1 _ |a Vehreschild, Janne
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700 1 _ |a Vogel, Jörg
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700 1 _ |a von Kleist, Max
|b 131
700 1 _ |a Walker, Andreas
|b 132
700 1 _ |a Walter, Jörn
|b 133
700 1 _ |a Wieczorek, Dagmar
|b 134
700 1 _ |a Winkler, Sylke
|b 135
700 1 _ |a Ziebuhr, John
|b 136
773 _ _ |a 10.1186/s13073-020-00823-5
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