S reaction to convert two molecules of fructose-6-phosphate and one molecule of 3PGA [19,31]. The coupling between the pentose phosphate pathway and catabolic processes is also apparent in the enrichment of GO terms in cluster 4. Here, the two considered reactions are only present in the extracted networks for the last time points. One of these reactions, phosphoglycerate mutase, takes part in glycolysis, which together with glucose consumption is reduced under low temperatures, especially in the early time points after stress [30]. Under heat stress, cluster 2 consists of profiles where the reactions are initially used, then excluded from the network, and finally reintroduced. Over-representation analysis demonstrates that catabolic processes involving amino acids, glyoxylate and coenzymes are enriched. Interestingly, the reactions in this cluster are also grouped together in cluster 2 under cold stress. However, it appears that after initial usage of the glycine cleavage system under heat stress, it is transiently shut down in a manner opposite of that under cold stress. Cluster 5 includes ammonium exchange which is downregulated after application of heat stress. This is in line with the catabolic processes observed in cluster 2, suggesting that protein synthesis is present to support maintenance of cell vitality without the need to sustain growth. In addition, cluster 3 under heat stress has a high overlap with cluster 3 under cold stress. However, the patternsof fractional appearance, as already observed for cluster 2, show a different temporal behavior. We therefore suggest the hypothesis that although same biological processes are involved in adaptation to temperature stresses, the temporal usage in terms of (in)activation may slightly differ. The activation pattern of these processes may further amplify the effect of genes specific to cold/heat stress.DiscussionHere we proposed a novel approach to investigate adaptation of metabolism upon external perturbation. Based on experimental data we determine time- and conditionspecific minimal networks for which sets of EFMs can be calculated. These sets are used to determine the fractional appearance profiles of reactions. This integrative profile combines information from transcriptomics data, the underlying network structure, and biologically meaningful flux distributions in a quasi steady-state; thus it includes information which transcriptomics data would never be able to reveal on their own. The fractional appearance of reactions has already been investigated with respect to the concept of robustness [13]. Here we demonstrate that expanding this concept to the time domain facilitates the distinction Capivasertib of two types of patterns–flat and fluctuating. In light of the differences as well as the overlap between the concepts of robustness and adaptability, the reactions exhibiting fluctuating patterns are the first candidates that drive the adaptation of the system upon perturbation. Moreover, like transcript data, the fractional appearance profiles can also be subjected to clustering and enrichment analyses (with respect to a chosen ontology). With the help of these analyses, our approach allows the identification PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/17139194 of adaptation-related processes. It must be noted that our proposed approach extracts network for individual time points, without accounting for their dependency in the time domain. However, since the weighting of the reactions is conducted by using data which already embed the.
