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 R. Cyr, David O. Okonkwo, Upendra K. Kar, Neha Krishnamoorthi, Robert Voinchet, Isabel M. Billiar, Mark H. Yazer, Rami A. Namas, Brian J. Daley, Richard S. Miller, Brian G. Harbrecht, Jeffrey A. Claridge, Herbert 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
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.