Pre-mRNA processing entropy in a mouse model of trauma

Abstract

PurposeNext generation sequencing has expanded our understanding of many disease processes, including trauma and critical illness. Many studies focus identifying a small set of genes or proteins that are aberrantly expressed. Our objective was to determine whether global differences in pre-mRNA processing entropy, or disorder, could offer novel insights in the setting of critical illness. MethodsWe used an established murine model of trauma that consisted of hemorrhagic shock and cecal ligation and puncture. In our first experiment mice exposed to trauma were compared to controls. In our second experiment, survival 14 days after exposure to trauma was studied. Using deep RNA sequencing we determined entropy values for every pre-mRNA processing event identified. We then used principal component analysis (PCA) to conduct unsupervised classification of the data. ResultsMice exposed to trauma separated from controls using PCA. Similarly, mice that did not survive 14 days post exposure clustered closely together on PCA. ConclusionOur results suggest that there is a substantial difference in global pre-mRNA processing entropy in mice exposed to trauma vs. controls, and that pre-mRNA processing entropy may be helpful in predicting mortality. The method introduced here is easily transferrable to other disease processes and samples.