TY - JOUR T1 - Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology A1 - Moss, Robert A1 - Grosse, Thibault A1 - Marchant, Ivanny A1 - Lassau, Nathalie A1 - Gueyffier, François A1 - Thomas, S. Randall Y1 - 2012/06/28 N2 - Author Summary As our understanding of the human body at all scales increases, the construction of a “Virtual Physiological Human” is becoming more feasible and will be an important step towards individualized diagnosis and treatment. As computational models increase in complexity to reflect this growth in understanding, analysis of these models becomes ever more complex. We present a methodology for systematically analysing the interactions between parameters and outputs of such complicated models, using the Guyton model of circulatory regulation as a case study. This model remains a landmark achievement that contributed to the development of our current understanding of blood pressure control, and we present the first comprehensive sensitivity analysis of this model. Effects of varying each parameter are explored over randomized simulations; our analysis demonstrates how to use these results to infer relationships between model parameters and the predicted physiological behaviour. Understanding these relationships is of the utmost importance for developing an optimal treatment strategy for individual patients. These results provide new insight into the multi-level interactions in the cardiovascular-renal system and will be useful to researchers wishing to use the model in pathophysiological or pharmacological settings. This methodology is applicable to current and future physiological models of arbitrary complexity. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 8 IS - 6 UR - https://doi.org/10.1371/journal.pcbi.1002571 SP - e1002571 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1002571 ER -