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In preparation for computing conserved protein interaction modules, we computed orthologous pairs of proteins in every pair of pathogens.

Then, for each of the 10000 resampled modules, we computed the median value of the correlation between its transcripts.

To compare the modules identified by an algorithm to the true modules, we computed the adjusted Rand Index [ 40].

As DME and Clique produced a large number of very similar modules, we computed for better comparability the number of distinct modules.

To determine if binding by the two TF groups and Suz12 occurs more often in certain modules we computed binding enrichment for each module.

To quantitatively assess the regulatory potential of each key TF to 8 functional modules, we computed the fold enrichment score (FES) defined by (the number of target genes within a module)/(the total number of genes within the module)/(the total number of target genes in the network)/(the total number of genes in the network).

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Similar(52)

Then for each module, we computed the proportion of module genes that could be best modeled by including the epistatic interactions.

For each such module we computed the significance of its overlap with all modules in the other three species (Methods).

For each module, we computed the phylogeny clustering of its member genes (see methods) using the K-statistics [ 41] in the picante package [ 42].

For each module, we computed enrichment scores [ 11] for the GO biological process, cellular component, and molecular function terms and for KEGG pathways.

The adjusted Rand Index can be computed by: (2) To assess the functional significance of gene modules, we first compute the enrichment of GO terms for the genes within each module.

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