Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia.
Wang, Y
Huang, X
Li, F
Jia, X
Jia, N
Fu, J
Liu, S
Zhang, J
Ge, H
Huang, S
Hui, Y
Sun, C
Xiao, F
Cui, X
Luu, LDW
Qu, D
Li, J
Tai, J
- Publisher:
- Springer Nature
- Publication Type:
- Journal Article
- Citation:
- Crit Care, 2023, 27, (1), pp. 79
- Issue Date:
- 2023-03-01
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Wang, Y | |
dc.contributor.author | Huang, X | |
dc.contributor.author | Li, F | |
dc.contributor.author | Jia, X | |
dc.contributor.author | Jia, N | |
dc.contributor.author | Fu, J | |
dc.contributor.author | Liu, S | |
dc.contributor.author | Zhang, J | |
dc.contributor.author | Ge, H | |
dc.contributor.author | Huang, S | |
dc.contributor.author | Hui, Y | |
dc.contributor.author | Sun, C | |
dc.contributor.author | Xiao, F | |
dc.contributor.author | Cui, X | |
dc.contributor.author | Luu, LDW | |
dc.contributor.author | Qu, D | |
dc.contributor.author | Li, J | |
dc.contributor.author | Tai, J | |
dc.date.accessioned | 2023-03-09T01:08:23Z | |
dc.date.available | 2023-02-21 | |
dc.date.available | 2023-03-09T01:08:23Z | |
dc.date.issued | 2023-03-01 | |
dc.identifier.citation | Crit Care, 2023, 27, (1), pp. 79 | |
dc.identifier.issn | 1364-8535 | |
dc.identifier.issn | 1466-609X | |
dc.identifier.uri | http://hdl.handle.net/10453/166743 | |
dc.description.abstract | OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. CONCLUSION: The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP. | |
dc.format | Electronic | |
dc.language | eng | |
dc.publisher | Springer Nature | |
dc.relation.ispartof | Crit Care | |
dc.relation.isbasedon | 10.1186/s13054-023-04378-w | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | 11 Medical and Health Sciences | |
dc.subject.classification | Emergency & Critical Care Medicine | |
dc.subject.mesh | Child | |
dc.subject.mesh | Child, Preschool | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Blood Coagulation | |
dc.subject.mesh | C-Reactive Protein | |
dc.subject.mesh | Cell Death | |
dc.subject.mesh | Community-Acquired Infections | |
dc.subject.mesh | Metabolomics | |
dc.subject.mesh | Proteomics | |
dc.subject.mesh | Pneumonia | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Community-Acquired Infections | |
dc.subject.mesh | C-Reactive Protein | |
dc.subject.mesh | Proteomics | |
dc.subject.mesh | Cell Death | |
dc.subject.mesh | Blood Coagulation | |
dc.subject.mesh | Child | |
dc.subject.mesh | Child, Preschool | |
dc.subject.mesh | Metabolomics | |
dc.title | Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia. | |
dc.type | Journal Article | |
utslib.citation.volume | 27 | |
utslib.location.activity | England | |
utslib.for | 11 Medical and Health Sciences | |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
utslib.copyright.status | open_access | * |
dc.date.updated | 2023-03-09T01:05:31Z | |
pubs.issue | 1 | |
pubs.publication-status | Published online | |
pubs.volume | 27 | |
utslib.citation.issue | 1 |
Abstract:
OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. CONCLUSION: The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.
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