Changes in network functionality. A large fractional appearance of a reaction > 자유게시판

Changes in network functionality. A large fractional appearance of a reaction does not only indicate its increased utilization, but also the activation of related processes, which result in an increased contribution of this reaction to the overall number of EFMs.yjNResultsw j ?vj (Inner)subject tomaximizej=Time- and condition-specific minimal operating networksvjNSij ?vj = 0 j D j Nsubject to yj = 0, 1,j=1 NFor both, cold and heat stress, the minimal networks include 416 to 427 metabolites interconnected by 480 to 486 reactions. The biomass Staurosporine production, as a result of the constraint from the minimization approach, ranges mol between 0.98 ?10-5 and 4.99 ?10-5 g W -hr .Comparison to networks extracted from MADEcj ?vi fminj=0 vj vmax ?yj , j 0 vj vmax , j j D(Outer),We compare the sets of reactions included in the timeand condition-specific networks extracted by both AdaM and MADE. We find that on average 66.6 of reactions are shared between the extracted networks over all time points and conditions, with larger average overlap for the?Topfer et al. BMC Systems Biology 2012, 6:148 http://www.biomedcentral.com/1752-0509/6/Page 5 ofheat condition of 67.2 (percentages with respect to the smaller network, i.e., the network extracted by AdaM). In addition, we determine the expected value of the overlap between the networks extracted by MADE and a random set of reactions of the same size as the networks extracted from our approach. By considering 1000 repetitions, we find this value to be 52.3 , thus confirming the similarity between the two approaches. The results are summarized in Tables 1 and 2.EFM-based characterization of adaptabilityTable 2 Comparison of the network overlap for the timeand condition-dependent minimal networks between AdaM and MADETime in min 10 20 30 40 50 60 70 average Cold 62.8 66.7 67.8 63.8 62.0 69.0 70.6 66.1 Heat 62.6 68.5 69.8 68.3 67.9 63.2 70.2 67.2 52.3 RandomThe number of EFMs in the minimal networks ranges between 1060 and 9582, which is small compared to other metabolic network models of similar size [13,18]. The extracted networks include only putatively active reactions and no inactive alternative pathways, and thus capture a specific metabolic state of low flexibility. In the following, the sets of EFMs are analyzed with respect to: (1) robustness to variations in the network extraction process, (2) stress adaptation of the network as a whole, and (3) the transitional behavior of individual reaction.Robustness of the optimization approachGiven is the overlap in of reactions included in the networks extracted by our approach PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16989806 and by MADE with respect to the smaller network. The average value for all time-dependent cold- and heat-shock specific networks are significantly higher than the values for a randomly drawn set of reactions of the same size.We investigate the robustness of the approach with respect to: (1) threshold variations for the optimization approach and (2) slightly suboptimal networks. To address the first aspect, we repeat the network minimization for three different thresholds to distinguish between dispensable and indispensable reactions. In addition, we examine three different values of minimal biomass production (i.e., 1 , 10 and 20 of the optimal biomass in the original network). To compare the results, we use the intersection of reactions in the minimal networks for each time point. The average overlap of reactions is 94.4 for cold and 94.3 for heat.