Francis MairetPlease use the format "First name initials family name" as in "Marie S. Curie, Niels H. D. Bohr, Albert Einstein, John R. R. Tolkien, Donna T. Strickland"
<p>Cells modulate their metabolism according to environmental conditions. A major challenge to better understand metabolic regulation is to identify, from the hundreds or thousands of molecules, the key metabolites where the re-orientation of fluxes occurs. Here, a method called ISIS (for In Silico Identification of Switches) is proposed to locate these nodes in a metabolic network, based on the analysis of a set of flux vectors (obtained e.g. by parsimonious flux balance analysis with different inputs). A metabolite is considered as a switch if the fluxes at this point are redirected in a different way when conditions change. The soundness of ISIS is shown with four case studies, using both core and genome-scale metabolic networks of <em>Escherichia coli</em>, <em>Saccharomyces cerevisiae</em> and the diatom<em> Phaeodactylum tricornutum</em>. Through these examples, we show that ISIS can identify hot-spots where fluxes are reoriented. Additionally, switch metabolites are deeply involved in post-translational modification of proteins, showing their importance in cellular regulation. In <em>P. tricornutum</em>, we show that Erythrose 4-phosphate is an important switch metabolite for mixotrophy suggesting the importance of this metabolite in the non-oxidative pentose phosphate pathway to orchestrate the flux variations between glycolysis, the Calvin cycle and the oxidative pentose phosphate pathway when the trophic mode changes. Finally, a comparison between ISIS and reporter metabolites identified with transcriptomic data confirms the key role of metabolites such as L-glutamate or L-aspartate in the yeast response to nitrogen input variation. Overall, ISIS opens up new possibilities for studying cellular metabolism and regulation, as well as potentially for developing metabolic engineering.</p>
