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 estimated the dispersions for whole blood log gene expressions in CAP and sepsis patients (8826 genes), and H1N1 infected patients (7240 genes) from the two data sets GSE65682 and GSE21802 respectively (for a detailed description of cohorts see original studies and Methods) [8, 11, 28] . For CAP and sepsis patients we also accounted for age, including it as a random variable in the Generalized Additive Model for Location, Scale and Shape (GAMLSS) [29] , see Methods. On average, the dispersions in log gene expressions in CAP, sepsis and H1N1 patients were significantly higher as compared to healthy individuals ( Figure 1A ). To that, for CAP patents' dispersions in log gene expressions were significantly higher for deceased patients as compared to those survived. Likewise, for H1N1 patients, dispersions in log gene expressions further increased in the late phase of infection ( Figure 1A ). For sepsis patients, on average dispersions in log gene expressions were comparable between survived and deceased patients for all analysed genes ( Figure 1A ). However, for genes for which dispersions changed significantly between healthy individuals and sepsis patients (Bonferroni adjusted p ≤ 0.05), their dispersions on average were higher in the deceased patients as compared to the survived (p < 0.001). Together, these suggest that host response to infection increases the biological coefficients of variations in genes' RNA copy numbers (as σ ) and substantiates heterogeneity in the pathogenesis of sepsis [8] from the gene expression perspective.