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

Sepsis is thought to trigger a plethora of heterogenous host responses to a systemic infection [5, 8] . We reasoned that this heterogeneity might be reflected in the inter-individual gene expression variability (standard deviation -ï€ ï³ or variance - 2 ). Considering that a) RNA copy number is a mixed Poisson (e.g. negative binomial) random variable [26] and that b) logtransformed microarray hybridization signal intensities correlate with log-transformed RNAseq copy numbers [27] . It is easy to show that the variance of log gene expression approximates the biological coefficient of variation (bcv 2 ) [20] . From the first-order Taylor expansion for variance: σ , where is the log gene expression. The mixed Poisson random variable, , where bcv 2 , also known as the overdispersion parameter, is independent of mean gene expression ( ). Thus, for ≫ 1 (for genes with a large mean RNA copy number), σ . In other words, by estimating the inter-individual log gene expression variabilities from either microarray signal intensities or RNA-seq counts we can infer approximately the biological coefficients of variations for genes' RNA copy numbers.