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

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

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Publisher:: Springer Nature
Publication Type:: Journal Article
Citation:: Crit Care, 2023, 27, (1), pp. 79
Issue Date:: 2023-03-01

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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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http://hdl.handle.net/10453/166743