The Molecular Atlas And Its Application For Trauma Patients By Multi-omics

Objectives: We aimed to build a temporal landscape by plasma multiomics in critically injured humans and reveal the application in early risk prediction and endotype identification.Methods: We analyzed a six-layer multi-omics dataset of trauma patients that includes clinical,cytokine,endotheliopathy biomarkers,lipidome,metabolome and proteome longitudinal information.Integrated clustering analysis were applied to identify the molecular patterns of trauma patients in hyperacute phase and 24 h or 72 h after admission.Machine learning methods were used to screen the prognostic biomarkers and.Unsupervised clustering was used to generate the endotypes by using the key patterns and molecules.Mutli-modal analysis including machine learning based dimension reduction,clustering,regression and prediction was used to analyze the dataset.All analysis were conducted in R software(v3.6.0).Results: The landscape of lipidome,metabolome and proteome in trauma patients were highly associated with the outcome.Integrated analysis reavealed a “Systemic Storm” pattern with release of 1061 markers together with a pattern suggestive of the “Massive Consumption” of 892 constitutive circulating markers in the hyper-acute phase post-trauma.Machine learning method screened and validated phosphatidylethanolamines(PE(18:0＿18:1)、PE(16:0＿22:6))elevated in patients with persistent critical illness and levels as prognostic biomarkers for worsen outcomes in trauma(AUC=0.873).Data integration yielded two human injury response endotypes,which aligned with clinical trajectory(HR:2.20;95%Cl:1.32-3.67,p=0.002).Prehospital allogeneic thawed plasma rescued only endotype 2 patients(“Systemic storm”)with traumatic brain injury(30d mortality: 30.3% vs.75.0%,p=0.0015).UCHL1 was identified as the most predictive circulating biomarker for patients most likely to benefit from early plasma treatment(AUC=0.915).Conclusions:(1)The multi-organ regulated “Systemic Storm” was the key host response in trauma patients;(2)Phospholipids can significantly improve the accuracy for prognosis prediction in critically injure humans;(3)The endotypes from molecular atlas could guide the use of thawed plasma in prehospital setting for trauma patients.These findings refine the paradigm of the human trauma response and can be used to guide further work on mechanistic study and clinical application.30 figures,3 tables,112 references...