Reply to "Do genome-scale models need exact solvers or clearer standards?".

Abstract

Mol Syst Biol. (2015) 11: 830 In their Correspondence entitled, “Do genome‐scale models need exact solvers or clearer standards?”, Ebrahim et al (2015) suggest an unnecessary dichotomy. They discuss the findings of our paper, “An exact arithmetic toolbox for a consistent and reproducible structural analysis of metabolic network models” (Chindelevitch et al , 2014), and suggest that our work highlights the need for better model encoding standards. Moreover, the authors dispute our claims that multiple previously published metabolic network models are unable to produce growth when analyzed with an exact arithmetic approach. They attribute discrepancies between their findings and ours solely to a misinterpretation of the formatting conventions used to encode these models. The authors conclude that genome‐scale metabolic network models need better standards, rather than the improvements in accuracy obtained with exact arithmetic. We argue here that improved standards and exact arithmetic are complementary advances that both benefit this field. Thus, the answer to the question posed by Ebrahim et al (2015) is “both.” In this response, we acknowledge the discrepancies in model interpretation between our approach and that of Ebrahim et al (2015), but maintain the key conclusions of our original study. Namely, a number of published metabolic network models are unable to exhibit growth even when our interpretation of these models is identical to that of Ebrahim et al (2015). We attribute the remaining differences between the results of our original study and their study to significant changes made to the models since our results were initially published. Indeed, our MONGOOSE tool provides a model verification platform, which will continue to be useful in identifying errors in model functionality, helping curators to fix them. Additionally, we demonstrate on a specific real‐model example that exact arithmetic can change the results of the analysis of genome‐scale metabolic network models. We conclude that exact arithmetic remains …