Patent ID: 7415359

Claim:
A method of predicting an altered physiological state of a cell comprising: (a) specifying a biochemical network of a cell; (b) simulating said network by (i) specifying the components of said network, (ii) representing interrelationships between said components in one or more mathematical equations and setting the quantitative parameters of said components, said mathematical equations including nonlinear differential equations where each such nonlinear differential equation includes the time rate of change of one or more gene products that comprise the biochemical network, and including various rate constants associated with said mathematical equations, and (iii) solving said mathematical equations to produce an initial simulated state of the cell; (c) optimizing said simulated biochemical network by determining and constraining the values of the parameters of said components by comparing experimental data regarding the value of at least one component with the value of said at least one component in said simulated biochemical network, said optimizing including comparing said simulation to at least one experimentally measured concentration time series and calculating an accuracy cost representing 2 a measure of the overall differences between the experimental data and the simulated time series; (d) perturbing the optimized simulated network by adding or deleting one or more components thereof, changing the concentration of one or more components thereof or modifying one or more mathematical equations representing interrelationships between one or more of said component, including modifying said rate constants away from their starting values; (e) solving the equations representing the perturbed network to simulate a modified state of the network, including calculating a new set of rate constants; (f) comparing said initial and modified simulated states of the network to identify the effect of said perturbation on the state of the network; (g) repeating said optimizing and said perturbing until the accuracy cost ceases to decrease by a defined increment; and (h) outputting the results of said comparison, the results of the perturbation(s) and the predicted state of the cell as perturbed to a user.