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

We noted in the introduction that due to a fluctuation-response a statistical inference of DGE might be biased towards genes with a high inter-individual variability, i.e. "noisy" genes ( Figure S1 ) [18, 19] . However, the same applies to ensemble gene noise ( Figure S4 ). This imposes a certain problem to the interpretation of both DGE and ensemble gene noise. On one hand, it can be suggested that large deviations in expression of genes and ensembles, which are naturally prone to high fluctuations, might not be causative for a disease, as an organism is already adapted to such variations. On the other hand, these genes/ensembles themselves might play an important adaptive role [41] and their over-response could lead to a disease. At the moment it seems difficult to come to a resolution between these two possibilities, but they . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 should be considered, specifically in identification of pharmaceutical targets: genes or gene ensembles (pathways, protein complexes).