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

• Published in: Cell reports. Medicine 2021-12, Vol.2 (12), p.100478-100478, Article 100478
• Main Authors: Wu, Junru, Vodovotz, Yoram, Abdelhamid, Sultan, Guyette, Francis X., Yaffe, Michael B., Gruen, Danielle S., Cyr, Anthony, Okonkwo, David O., Kar, Upendra K., Krishnamoorthi, Neha, Voinchet, Robert G., Billiar, Isabel M., Yazer, Mark H., Namas, Rami A., Daley, Brian J., Miller, Richard S., Harbrecht, Brian G., Claridge, Jeffrey A., Phelan, Herbert A., Zuckerbraun, Brian S., Johansson, Pär I., Stensballe, Jakob, Morrissey, James H., Tracy, Russell P., Wisniewski, Stephen R., Neal, Matthew D., Sperry, Jason L., Billiar, Timothy R.
• Format: Article
• Language: English
• Subjects: Brain Injuries, Traumatic - genetics; Brain Injuries, Traumatic - therapy; Cluster Analysis; Cohort Studies; endotype; Genomics; host response; Humans; Metabolome; metabolomics; multi-omics; outcome; PAMPer trial; Plasma; Proteome - metabolism; proteomics; systemic storm; thawed plasma; Time Factors; trauma; Treatment Outcome
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2021.100478

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. [Display omitted] An integrated longitudinal multi-omic analysis of the human response to traumaSystemic storm and massive consumption patterns are related to early mortalityUnique resolution and non-resolution signatures across multiple “omics” platformsOnly endotype 2-TBI patients with high UCHL1 levels benefit from early plasma Wu et al. report a longitudinal multi-omic analysis of the circulation in trauma patients. Cross-platform data integration reveals a massive systemic release of cellular contents (“systemic storm”) and simultaneous consumption of blood constituents. Also defined are patient endotypes that differ in outcomes and responses to early plasma administration.