@article{5c1715ea591d44c587a0c7c16f43c01f,
title = "Multi-omic analysis in injured humans: Patterns align with outcomes and treatment responses",
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.",
keywords = "PAMPer trial, endotype, host response, metabolomics, multi-omics, outcome, proteomics, systemic storm, thawed plasma, trauma",
author = "{PAMPer study group} and Junru Wu and Yoram Vodovotz and Sultan Abdelhamid and Guyette, {Francis X.} and Yaffe, {Michael B.} and Gruen, {Danielle S.} and Anthony Cyr and Okonkwo, {David O.} and Kar, {Upendra K.} and Neha Krishnamoorthi and Voinchet, {Robert G.} and Billiar, {Isabel M.} and Yazer, {Mark H.} and Namas, {Rami A.} and Daley, {Brian J.} and Miller, {Richard S.} and Harbrecht, {Brian G.} and Claridge, {Jeffrey A.} and Phelan, {Herbert A.} and Zuckerbraun, {Brian S.} and Johansson, {P{\"a}r I.} and Jakob Stensballe and Morrissey, {James H.} and Tracy, {Russell P.} and Wisniewski, {Stephen R.} and Neal, {Matthew D.} and Sperry, {Jason L.} and Billiar, {Timothy R.}",
note = "Funding Information: This work was supported by US Army Medical Research and Materiel Command ( W81XWH-12-2-0023 to J.L.S.) and National Institutes of Health ( R35-GM-127027 to T.R.B.; R35GM119526 and R01HL141080 to M.D.N.; UM1HL120877 to J.H.M. and S.R.W. with sub-award to M.D.N.). We acknowledge the contribution of collaborators involved in PAMPer study for the clinical data collection. We acknowledge the contribution of the TACTIC team for proteomic data collection. J.W. was supported by Xiangya Medical School, Changsha, China. Funding Information: This work was supported by US Army Medical Research and Materiel Command (W81XWH-12-2-0023 to J.L.S.) and National Institutes of Health (R35-GM-127027 to T.R.B.; R35GM119526 and R01HL141080 to M.D.N.; UM1HL120877 to J.H.M. and S.R.W. with sub-award to M.D.N.). We acknowledge the contribution of collaborators involved in PAMPer study for the clinical data collection. We acknowledge the contribution of the TACTIC team for proteomic data collection. J.W. was supported by Xiangya Medical School, Changsha, China. Conceptualization, J.W. and T.R.B.; methodology, J.W. Y.V. and D.J.G.; software, J.W.; validation, J.W. S.A. and R.A.N.; formal analysis, J.W. S.A. N.K. R.G.V. and I.M.B.; investigation, J.W. D.S.G. A.C. P.I.J. J.S. and D.O.O.; resources, J.L.S. F.X.G. M.D.N. J.H.M. R.P.T. M.H.Y. B.J.D. R.S.M. B.G.H. J.A.C. H.A.P. S.R.W. B.S.Z. and T.R.B.; data curation, J.W. J.L.S. and R.A.N.; writing ? original draft, J.W. and T.R.B.; writing ? review & editing, J.W. Y.V. S.A. F.X.G. M.B.Y. D.O.O. M.D.N. J.L.S. and T.R.B.; visualization, J.W.; supervision, Y.V. M.D.N. J.L.S. and T.R.B.; project administration, J.W. U.K.K. J.H.M. M.D.N. J.L.S. and T.R.B.; funding acquisition, M.D.N. J.L.S. and T.R.B. Y.V. is co-founder and a stakeholder in Immunetrics. H.A.P. is a consultant for Avita Medical and Spectral MD. M.D.N. holds an equity stake in Haima Therapeutics. He has received research support and/or honoraria from Haemonetics, Instrumentation Laboratories, and Janssen Pharmaceuticals. T.R.B. is a stakeholder in Immunetrics. Other authors declare no conflict of interests. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = dec,
day = "21",
doi = "10.1016/j.xcrm.2021.100478",
language = "English",
volume = "2",
journal = "Cell Reports Medicine",
issn = "2666-3791",
number = "12",
}