Multi-omic analysis in injured humans: Patterns align with outcomes and treatment responses

Junru Wu; Yoram Vodovotz; Sultan Abdelhamid; Francis X Guyette; Michael B Yaffe; Danielle S Gruen; Anthony Cyr; David O Okonkwo; Upendra K Kar; Neha Krishnamoorthi; Robert G Voinchet; Isabel M Billiar; Mark H Yazer; Rami A Namas; Brian J Daley; Richard S Miller; Brian G Harbrecht; Jeffrey A Claridge; Herbert A Phelan; Brian S Zuckerbraun; Pär I Johansson; Jakob Stensballe; James H Morrissey; Russell P Tracy; Stephen R Wisniewski; Matthew D Neal; Jason L Sperry; Timothy R Billiar; PAMPer study group

doi:10.1016/j.xcrm.2021.100478

Multi-omic analysis in injured humans: Patterns align with outcomes and treatment responses

Junru Wu, Yoram Vodovotz, Sultan Abdelhamid, Francis X Guyette, Michael B Yaffe, Danielle S Gruen, Anthony Cyr, David O Okonkwo, Upendra K Kar, Neha Krishnamoorthi, Robert G Voinchet, Isabel M Billiar, Mark H Yazer, Rami A Namas, Brian J Daley, Richard S Miller, Brian G Harbrecht, Jeffrey A Claridge, Herbert A Phelan, Brian S ZuckerbraunPär I Johansson, Jakob Stensballe, James H Morrissey, Russell P Tracy, Stephen R Wisniewski, Matthew D Neal, Jason L Sperry, Timothy R Billiar, PAMPer study group

55 Citationer (Scopus)

Abstract

Trauma is a leading cause of death and morbidity worldwide. Here, we present the analysis of a longitudinal multi-omic dataset comprising clinical, cytokine, endotheliopathy biomarker, lipidome, metabolome, and proteome data from severely injured humans. A "systemic storm" pattern with release of 1,061 markers, together with a pattern suggestive of the "massive consumption" of 892 constitutive circulating markers, is identified in the acute phase post-trauma. Data integration reveals two human injury response endotypes, which align with clinical trajectory. Prehospital thawed plasma rescues only endotype 2 patients with traumatic brain injury (30-day mortality: 30.3 versus 75.0%; p = 0.0015). Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) was identified as the most predictive circulating biomarker to identify endotype 2-traumatic brain injury (TBI) patients. These response patterns refine the paradigm for human injury, while the datasets provide a resource for the study of critical illness, trauma, and human stress responses.

Originalsprog	Engelsk
Artikelnummer	100478
Tidsskrift	Cell reports. Medicine
Vol/bind	2
Udgave nummer	12
Sider (fra-til)	100478
Antal sider	23
ISSN	2666-3791
DOI	https://doi.org/10.1016/j.xcrm.2021.100478
Status	Udgivet - 21 dec. 2021

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Wu, J., Vodovotz, Y., Abdelhamid, S., Guyette, F. X., Yaffe, M. B., Gruen, D. S., Cyr, A., Okonkwo, D. O., Kar, U. K., Krishnamoorthi, N., Voinchet, R. G., Billiar, I. M., Yazer, M. H., Namas, R. A., Daley, B. J., Miller, R. S., Harbrecht, B. G., Claridge, J. A., Phelan, H. A., ... PAMPer study group (2021). Multi-omic analysis in injured humans: Patterns align with outcomes and treatment responses. Cell reports. Medicine, 2(12), 100478. Artikel 100478. https://doi.org/10.1016/j.xcrm.2021.100478

Wu, J, Vodovotz, Y, Abdelhamid, S, Guyette, FX, Yaffe, MB, Gruen, DS, Cyr, A, Okonkwo, DO, Kar, UK, Krishnamoorthi, N, Voinchet, RG, Billiar, IM, Yazer, MH, Namas, RA, Daley, BJ, Miller, RS, Harbrecht, BG, Claridge, JA, Phelan, HA, Zuckerbraun, BS, Johansson, PI , Stensballe, J, Morrissey, JH, Tracy, RP, Wisniewski, SR, Neal, MD, Sperry, JL, Billiar, TR & PAMPer study group 2021, 'Multi-omic analysis in injured humans: Patterns align with outcomes and treatment responses', Cell reports. Medicine, bind 2, nr. 12, 100478, s. 100478. https://doi.org/10.1016/j.xcrm.2021.100478

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abstract = "Trauma is a leading cause of death and morbidity worldwide. Here, we present the analysis of a longitudinal multi-omic dataset comprising clinical, cytokine, endotheliopathy biomarker, lipidome, metabolome, and proteome data from severely injured humans. A {"}systemic storm{"} pattern with release of 1,061 markers, together with a pattern suggestive of the {"}massive consumption{"} of 892 constitutive circulating markers, is identified in the acute phase post-trauma. Data integration reveals two human injury response endotypes, which align with clinical trajectory. Prehospital thawed plasma rescues only endotype 2 patients with traumatic brain injury (30-day mortality: 30.3 versus 75.0%; p = 0.0015). Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) was identified as the most predictive circulating biomarker to identify endotype 2-traumatic brain injury (TBI) patients. These response patterns refine the paradigm for human injury, while the datasets provide a resource for the study of critical illness, trauma, and human stress responses.",

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AU - Gruen, Danielle S

AU - Cyr, Anthony

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AU - Namas, Rami A

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AU - Claridge, Jeffrey A

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AU - Zuckerbraun, Brian S

AU - Johansson, Pär I

AU - Stensballe, Jakob

AU - Morrissey, James H

AU - Tracy, Russell P

AU - Wisniewski, Stephen R

AU - Neal, Matthew D

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AU - Billiar, Timothy R

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Multi-omic analysis in injured humans: Patterns align with outcomes and treatment responses

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