Development of a biomarker prediction model for post-trauma multiple organ failure/dysfunction syndrome based on the blood transcriptome.

Abstract

Multiple organ failure/dysfunction syndrome (MOF/MODS) is a major cause of mortality and morbidity among severe trauma patients. Current clinical practices entail monitoring physiological measurements and applying clinical score systems to diagnose its onset. Instead, we aimed to develop an early prediction model for MOF outcome evaluated soon after traumatic injury by performing machine learning analysis of genome-wide transcriptome data from blood samples drawn within 24h of traumatic injury. We then compared its performance to baseline injury severity scores and detection of infections. Buffy coat transcriptome and linked clinical datasets from blunt trauma patients from the Inflammation and the Host Response to Injury Study ("Glue Grant") multi-center cohort were used. According to the inclusion/exclusion criteria, 141 adult (age ≥ 16years old) blunt trauma patients (excluding penetrating) with early buffy coat (≤ 24h since trauma injury) samples were analyzed, with 58 MOF-cases and 83 non-cases. We applied the Least Absolute Shrinkage and Selection Operator (LASSO) and eXtreme Gradient Boosting (XGBoost) algorithms to select features and develop models for MOF early outcome prediction. The LASSO model included 18 transcripts (AUROC [95% CI]: 0.938 [0.890-0.987] (training) and 0.833 [0.699-0.967] (test)), and the XGBoost model included 41 transcripts (0.999 [0.997-1.000] (training) and 0.907 [0.816-0.998] (test)). There were 16 overlapping transcripts comparing the two panels (0.935 [0.884-0.985] (training) and 0.836 [0.703-0.968] (test)). The biomarker models notably outperformed models based on injury severity scores and sex, which we found to be significantly associated with MOF (APACHEII + sex-0.649 [0.537-0.762] (training) and 0.493 [0.301-0.685] (test); ISS + sex-0.630 [0.516-0.744] (training) and 0.482 [0.293-0.670] (test); NISS + sex-0.651 [0.540-0.763] (training) and 0.525 [0.335-0.714] (test)). The accurate assessment of MOF from blood samples immediately after trauma is expected to aid in improving clinical decision-making and may contribute to reduced morbidity, mortality and healthcare costs. Moreover, understanding the molecular mechanisms involving the transcripts identified as important for MOF prediction may eventually aid in developing novel interventions.