A null biomass if one of the component of the biomass

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An additional 3 Cited as a crucial contributor to variability of retention and poor essential gene pairs involving 6 new unique genes were found using SA. All essential pairs identified by title= per.1944 both SA and FBA are isoenzymes whose removal results in a total arrest of biomass production. Isoenzymes usually result in a higher biomass loss than relatively distant pairs (Figure 2). For the 12 isoenzymes, the deletion of the two genes in a pair is required to remove a reaction that is catalysed by both. For the remaining essential gene pairs, the reactions associated with both genes are used in parallel in the wild type, a case of metabolicplasticity [61], or the reactions from only one of the genes is used while the reaction from the other member of the pair can act as a backup, a case of metabolic redundancy [61]. Depending on the category in which an essential gene pair falls, different strategies may be required in order to target the pair [61]. From the 39 essential genes pairs, 23 represent cases of plasticity of the network and 4 cases of redundancy in the network (Additional file 1: Table S9).Distribution of predicted essential genes across pathwaysIn order to see which parts of title= fnhum.2013.00596 metabolism are more enriched with essential genes, we classified reactions into 8 functional pathway classifications (Additional file 1: Table S10). A hypergeometric test [62] for over and under-representation was performed to identify pathways enrichment in essential genes. This analysis confirmed that linear pathways, like lipid synthesis, tend to have more essential genes (25 out of 71 single gene deletions, overrepresentation p-value 1.81e-10) due to the lack of alternative ways leading to the production of biomass metabolites (Figure 3, Additional file 1: Table S11).Potential compounds binding predicted essential targetsMolecules potentially binding the proteins encoded by the 123 genes identified as potential targets on their ownLarocque et al.A null biomass if one of the component of the biomass was impossible to produce otherwise they were arbitrary attributed an effect of 5-10 since the number of reaction required to produce biomass augmented by less than 10 in every cases. The number of cases in the unlabelled sections of the pie chart is in clockwise order 1, 1, 3 and 1.We performed double gene deletions to identify potential polypharmacological targets and to target reactions that are catalyzed by isoenzymes. Based on FBA analysis, 203 gene pairs involving 69 unique genes that had small or no effect in single gene deletion were deleterious when removed in pairs. An additional 3 essential gene pairs involving 6 new unique genes were found using SA. Eight gene pairs were considered essential in both SA and FBA (Additional file 1: Table S8). Some double mutants show a synergistic effect, defined as an effect greater that an additional 1 reduction in biomass production in the double mutant than the sum of effects of each single mutant. The 39 synergistic double mutants were analysed in more detail (Additional file 1: Table S9). Thirteen of these synergistic gene combinations resulted in total abolition of biomass production in FBA or prevented the biosynthesis of at least one element of the biomass in SA, 11 had an effect between 10 and 20 and the remaining 15 had a small effect on biomass production (between 5 and 10 ).