Reaction enrichment analysis

Hypergeometric enrichment was used to obtain HumanGEM subsystems[25] (S2 Dataset) which are overrepresented in the altered set of reactions. Briefly, the enriched reaction list obtained from above was used to conduct a two-tailed hypergeometric test. Here, adjusted p-value was used to obtain the pathways showing significant representation based on the constituent altered reactions.

Here, P(X = k) is the probability that we find k reactions just by chance in a given subsystem. K is the total number of reactions belonging to a given subsystem, N is the total number of reactions in the model and n is the total number of reactions that show altered flux as calculated by differential flux analysis. For each subsystem in the model, we conducted a hypergeometric enrichment test for overrepresentation. If P(X = k)<0.05, then it is likely that the over-representation of the subsystem is due to the high number of altered reactions in the pathway rather than by chance. The resulting p-values for pathways were again subjected to multiple-hypothesis correction using Benjamini-Hochberg method using False Discovery Rate (FDR) with α = 0.05. From this, we were able to obtain the pathways in the HumanGEM model which are most affected by the infection.