Trans-omics analysis of post-injury thromboinflammation plasma identifies endotypes and trajectories in trauma patients

Understanding and managing the complexity of trauma-induced
thromboinflammation necessitates an innovative, data-driven approach. This
study leveraged a trans-omics analysis of 759 longitudinal samples from
118 trauma patients and 97 healthy controls to illuminate molecular
endotypes and trajectories that underpin patient outcomes. We hypothesized
that unsupervised trans-omics profiling would reveal underlying clinical
differences in injured patients that may present with similar clinical
characteristics but ultimately have different outcomes. Here, we used
proteomics and metabolomics to profile longitudinal plasma samples from
trauma patients and healthy controls. Omics-based patient states were
defined to map unique pathophysiologic states encountered by trauma
patients over time. Then, patients were endotyped according to their
longitudinal trajectory through trauma omics states, and injury patterns
and outcomes were compared. Importantly, endotypes without significant
differences in injury patterns yet with different clinical outcomes were
identified. Organ failure among these similarly injured patients was
predicted with higher accuracy using omics markers over injury covariates.
Patients who presented with elevated proteosome activation, catabolism,
and superoxide formation were vulnerable to heart and lung failure, and
ALI, respectively. Additionally, hypoxia, RBC lysis, and hydrolase omics
markers out-predicted injury covariates for mortality and intensive care
across all trauma patients. Injury and outcome patterns persisted in an
independent validation cohort of 333 patients from the Trauma Activation
Protocol trial following trajectory prediction using a single, early
timepoint. This strategy aligns with our understanding that trauma
patients, despite similar clinical presentation, might harbor vastly
different biological responses and outcomes. Further, this work presents a
novel framework for personalized trauma patient treatment by mapping
patient trajectory through injury and recovery.