Suitability and utility of computational analysis tools: characterization of erythrocyte parameter variation

Systems engineering can provide insights into multivariate regulatory networks and pooling in complex biological networks that cannot be fully interpreted through experiments alone. Herein, we analyzed the use of phase planes, modal and time-lagged correlation (TLC) analyses of the human erythrocyte to explore the utility of these techniques for understanding the effect of single parameter changes on the behavior of a metabolic network. Specifically, several parameters in key regulatory steps in erythrocyte glycolysis, Rapoport-Leubering bypass, pentose phosphate pathway, adenosine metabolism, and membrane transport were perturbed. The most sensitive parameters were identified based on the steady-state metabolite concentration changes and were explored further. Modal analysis identified relevant time scales for each parameter change. These time scales were further explored using phase plane and TLC analyses. Phase plane and TLC both inferred pooling changes, while TLC also identified changes in the regulatory network structure that resulted from various parameter changes. Each method has strengths and weaknesses for exploring and gaining insight into complex biological networks.