G relevant experimental information. We hope that in addition to being

We hope that in addition to being a tool to aggregate existing knowledge, iMLTC806cdf will prove to be valuable as a nucleation point in developing our understanding of this important human pathogen driving the generation of new experimental hypotheses.The analysis of a metabolic network in isolation in the Ts she or he fights all through the game (anything that gives absence of other relevant processes present in the organism poses its own problems. acetobutylicum network [26] indicates that both bacteria share the same metabolic core. Existing differences in reactions and associated genes may explain the differences obtained while comparing the effects of deleted genes and reactions. The different media utilized for both bacteria may also cause some differences. The comparison with experimental results for B. subtillis [47] was used as validation due to the absence of experimental results for the gene essentiality in C. difficile. While essential differences exist between the two organisms, a large degree of conservation is also present. Therefore one should expect that a large number of genes conserve their essentiality across these two species. The high level of accuracy (according to functional or sequence homology) between the experimental results and our predictions serves as a validation of iMLTC806cdf as a mature draft metabolic network and increases our confidence in the list of predicted essential genes. One important difference between the metabolism of C. difficile and B. subtilis is that the later can use oxygen to produce energy while the former cannot. Therefore, predicted essential C. difficile genes involved in fermentation such as pykF or ackA are not essential in B. subtilis. Other genes such as fabH, CD1966 and ribC are only present in one copy in C. difficile while more than one gene catalyses the same reactions in B. subtilis [71], explaining why such genes are non-essential in the latter.Larocque et al. BMC Systems Biology 2014, 8:117 http://www.biomedcentral.com/1752-0509/8/Page 12 ofSome genes whose inactivation is deleterious in v.G relevant experimental information. We hope that in addition to being a tool to aggregate existing knowledge, iMLTC806cdf will prove to be valuable as a nucleation point in developing our understanding of this important human pathogen driving the generation of new experimental hypotheses.The analysis of a metabolic network in isolation in the absence of other relevant processes present in the organism poses its own problems. For example, the effect of metabolites (such as pyridoxine and biotin) [37] involved in nonmetabolic processes could not be simulated. Likewise, methionine added to minimal media greatly increases growth in vitro [36] but the addition of methionine to the minimal media in iMLTC806cdf increases biomass by less than 1 . Methionine is mostly used in the bacteria as S-adenosyl methionine involved in the biosynthesis of cofactors and vitamins which are not directly involved in biomass synthesis and have an effect that cannot be simulated in the metabolic network [70]. While the removal of methionine produced a qualitatively correct outcome, the loss of biomass in the network when removing methionine from the minimal medium is only due to the additional reactions required to produce enough methionine as required for biomass production. The case of pantothenate, the only essential vitamin with a clear metabolic effect title= journal.pone.0158910 is unique, as its essentiality is strain-dependant.