Discovery of pharmaceutically-targetable pathways and prediction of survivorship for pneumonia and sepsis patients from the view point of ensemble gene noise

Tristan de Jong; Victor Guryev; Yury M. Moshkin

. CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.10.035717 doi: bioRxiv preprint Indeed, it has been established that the activity of the Complex I is decreased and correlates with the severity of sepsis [30] . Complex I is the first set of enzymes of the respiratory chain and it is the entry point for most electrons into the electron transport chain [31] . Interestingly, however, in case of the Complex I inhibition or deregulation, methylene blue (MB) can bypass it by acting as alternative redox mediator in the electron transport chain, thus, restoring mitochondrial respiration [32, 33] (Figure 2D ). MB is also considered to be a promising therapeutic in treatment of septic shock [34, 35] . Thus, ensemble gene noise might provide a simple yet powerful explanatory shortcut, from the expression of thousands of genes to the function of gene ensembles and possible pharmaceutical targets.