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

Cell Rep Med. 2021 Dec 21;2(12):100478. doi: 10.1016/j.xcrm.2021.100478.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Brain Injuries, Traumatic / genetics*
  • Brain Injuries, Traumatic / therapy*
  • Cluster Analysis
  • Cohort Studies
  • Genomics*
  • Humans
  • Metabolome
  • Plasma
  • Proteome / metabolism
  • Time Factors
  • Treatment Outcome

Substances

  • Proteome