Significant correlations between the evolutionary rates of proteins and the average rates of their network neighbours, except for the transcription regulation network.

1<p>Spearman's rank correlation coefficient.</p

Correlation between <i>dN</i> and average <i>dN</i> of the neighbours after controlling separately for protein abundance, codon usage (CAI), or mRNA expression level; and after simultaneously controlling for all three expression measures and for protein length, gene essentiality, and network connectivity using a linear model.

1<p>Partial regression coefficient.</p>2<p>Percent of variation in <i>dN</i> explained by average neighbour <i>dN</i> independently of the other variables, and 95% confidence intervals (calculated using a relative importance measure that averages over orderings of regressors, with confidence intervals based on 1000 bootstraps <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0018288#pone.0018288-Grmping1" target="_blank">[43]</a>). This combined analysis was only performed if controlling for individual variables did not remove the correlation with <i>dN</i>.</p

Definitions of the sets used in the system of equations that describes the GlobalFit algorithm.

<p>Definitions of the sets used in the system of equations that describes the GlobalFit algorithm.</p

Comparison of experimental and predicted viability for 187 M. genitalium gene knockouts.

<p>Comparison of experimental and predicted viability for 187 M. genitalium gene knockouts.</p

Metabolite additions to the <i>E</i>. <i>coli</i> biomass reaction suggested by GlobalFit to resolve FPp.

<p>Metabolite additions to the <i>E</i>. <i>coli</i> biomass reaction suggested by GlobalFit to resolve FPp.</p

The parameters of the system of equations describing the GlobalFit algorithm.

<p>The parameters of the system of equations describing the GlobalFit algorithm.</p

Reversal of reactions of the <i>E</i>. <i>coli</i> network suggested by GlobalFit to remove FNp.

<p>Reversal of reactions of the <i>E</i>. <i>coli</i> network suggested by GlobalFit to remove FNp.</p

Removal of reactions of the <i>E</i>. <i>coli</i> network suggested by GlobalFit to correct FPp.

<p>Removal of reactions of the <i>E</i>. <i>coli</i> network suggested by GlobalFit to correct FPp.</p

Comparison of experimental and predicted viability for 1366 <i>E</i>. <i>coli</i> gene knockouts on two different minimal media.

<p>Comparison of experimental and predicted viability for 1366 <i>E</i>. <i>coli</i> gene knockouts on two different minimal media.</p

Modifications of the <i>M</i>. <i>genitalium</i> network suggested by GlobalFit based on 187 gene knockout experiments (bold font indicates conservative changes).

<p>Modifications of the <i>M</i>. <i>genitalium</i> network suggested by GlobalFit based on 187 gene knockout experiments (bold font indicates conservative changes).</p