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

In this study we applied the concept of ensemble gene noise to the analysis of critically ill H1N1, CAP and sepsis patients [8, 28] . We noted a large-scale gene response in two dimensions: on the level of mean gene expression and on the level of variance (inter-individual variability). Interestingly, both responses were correlated ( Figure 1D ) and both were dependent on gene variance suggesting that the fluctuation-response might drive changes in these two parameters of gene expression co-ordinately [18] . In all three cases (H1N1, CAP and sepsis), inter-individual variability was increased for a bulk of the genes. Consequently, we only identified pathways or gene complexes for which ensemble gene noise was significantly increased for H1N1, CAP and sepsis patients as compared to healthy individuals. This suggests that inter-individual gene expression variability is a prominent driver of ensemble gene noise in these patients.