Illustration of presented flux balance approach to predict life cycle specific metabolism. Given the gene expression data (blue table) flux distributions (red arrows) within the shown example metabolic network (blue arrows) can be inferred for time points t1 and t2 as depicted in (A). However, neither flux direction nor flux strength can be deduced from gene expression alone (indicated by question marks next to flux arrows). The set of all possible flux distributions that are consistent with the gene expression data can be reduced by knowledge about target fluxes such as biomass production (i). Reactions that are not supported by genome annotation might represent errors in the network assembly. Therefore it is desirable to prevent the usage of such reactions in calculated flux distributions (ii). An enzyme or a transporter that is able to process different metabolites does not necessarily convert all substrates at same rates. If one reaction product is not converted further by subsequent enzymes, it accumulates and as a consequence the net production rate is close to zero, even if the gene is expressed and substrate is available (iii). The flux solution space can be narrowed down further when assuming that biomass production is achieved with a minimal amount of nutrients (iv), which are of varying availability (v). Gene products can be present within a cell, even when the gene transcript is not detectable, as proteins appear later than the corresponding mRNA and protein degradation might be delayed compared to mRNA degradation. Considering proteins to be present whose transcript was detectable during a previous time point (vi) presumably reflects the actual cellular status better than taking only the current transcription snapshot into account. The flux distribution calculated by our flux balance approach, which incorporates all these issues, is shown in (B).
Huthmacher et al. BMC Systems Biology 2010 4:120 doi:10.1186/1752-0509-4-120