Simulations networked activity using dynamics-based constraints on reusable network component

Abstract

Techniques for simulating networks using dynamics-based constraints are disclosed.

What is claimed is: 
     
         1 . A system for using a simulator to generate metabolite time course data comprising:
 one or more data processors; and   a non-transitory computer readable storage medium containing instructions which, when executed on the one or more data processors, cause the one or more data processors to perform actions including:
 defining one or more modules within a biological system based on corresponding biological functions; 
 defining a set of reactions for the one or more modules within the biological system, wherein the set of reactions indicate how various molecules are consumed and produced through at least a portion of a life cycle of the biological system, and wherein each reaction of the set of reactions identifies stoichiometry indicative of one or more metabolites that are consumed, one or more metabolites that are produced and, for each consumed and produced metabolite, a coefficient indicating a relative amount that is consumed or produced; 
 identifying one or more additional constraints for the set of reactions; 
 defining an objective function for the set of reactions based on the stoichiometries of the set of reactions; and 
 executing a simulation using the set of reactions, the one or more additional constraints, and the objective function to generate the metabolite time course data for a given time point. 
   
     
     
         2 . The system of  claim 1 , wherein the actions further include:
 determining an availability value for each metabolite related to the set of reactions, wherein executing the simulation includes determining, for each reaction of the set of reactions, a flux of the reaction based on the availability values, the one or more additional constraints, and the objective function; and   updating a centralized availability value for each metabolite based on the identified fluxes.   
     
     
         3 . The system of  claim 2 , wherein the fluxes indicate a number of times that each reaction of the set of reactions were performed in the simulation in accordance with the availability values, the one or more additional constraints, and the objective function. 
     
     
         4 . The system of  claim 1 , wherein the set of reactions further identify one or more enzymes, one or more cofactors, one or more characteristics that are required for a reaction to occur, one or more characteristics that affects a probability of the reaction occurring, one or more properties of the reaction, or any combination thereof. 
     
     
         5 . The system of  claim 1 , wherein the one or more additional constraints include a flux lower bound and/or a flux upper bound to limit a flux, a quantity of a consumed or produced metabolite, a kinetic constant, a rate of production or decay of a component, an enzyme concentration or activity, a compartment size, a concentration of an external metabolite, or any combination thereof. 
     
     
         6 . The system of  claim 1 , wherein the actions further include, for a subsequent time point:
 identifying one or more additional constraints for the set of reactions;   defining an objective function for the set of reactions based on the stoichiometries of the set of reactions; and   executing a simulation using the set of reactions, the one or more additional constraints, and the objective function to generate the metabolite time course data for the subsequent time point.   
     
     
         7 . The system of  claim 1 , wherein the objective function identifies one or more metrics that are to be maximized and/or minimized when identifying a solution. 
     
     
         8 . A computer-implemented method comprising:
 defining one or more modules within a biological system based on corresponding biological functions;   defining a set of reactions for the one or more modules within the biological system, wherein the set of reactions indicate how various molecules are consumed and produced through at least a portion of a life cycle of the biological system, and wherein each reaction of the set of reactions identifies stoichiometry indicative of one or more metabolites that are consumed, one or more metabolites that are produced and, for each consumed and produced metabolite, a coefficient indicating a relative amount that is consumed or produced;   identifying one or more additional constraints for the set of reactions;   defining an objective function for the set of reactions based on the stoichiometries of the set of reactions; and   executing a simulation using the set of reactions, the one or more additional constraints, and the objective function to generate the metabolite time course data for a given time point.   
     
     
         9 . The computer-implemented method of  claim 8 , further comprising:
 determining an availability value for each metabolite related to the set of reactions, wherein executing the simulation includes determining, for each reaction of the set of reactions, a flux of the reaction based on the availability values, the one or more additional constraints, and the objective function; and   updating a centralized availability value for each metabolite based on the identified fluxes.   
     
     
         10 . The computer-implemented method of  claim 9 , wherein the fluxes indicate a number of times that each reaction of the set of reactions were performed in the simulation in accordance with the availability values, the one or more additional constraints, and the objective function. 
     
     
         11 . The computer-implemented method of  claim 8 , wherein the set of reactions further identify one or more enzymes, one or more cofactors, one or more characteristics that are required for a reaction to occur, one or more characteristics that affects a probability of the reaction occurring, one or more properties of the reaction, or any combination thereof. 
     
     
         12 . The computer-implemented method of  claim 8 , wherein the one or more additional constraints include a flux lower bound and/or a flux upper bound to limit a flux, a quantity of a consumed or produced metabolite, a kinetic constant, a rate of production or decay of a component, an enzyme concentration or activity, a compartment size, a concentration of an external metabolite, or any combination thereof. 
     
     
         13 . The computer-implemented method of  claim 8 , further comprising, for a subsequent time point:
 identifying one or more additional constraints for the set of reactions;   defining an objective function for the set of reactions based on the stoichiometries of the set of reactions; and   executing a simulation using the set of reactions, the one or more additional constraints, and the objective function to generate the metabolite time course data for the subsequent time point.   
     
     
         14 . The computer-implemented method of  claim 8 , wherein the objective function identifies one or more metrics that are to be maximized and/or minimized when identifying a solution. 
     
     
         15 . A computer-program product tangibly embodied in a non-transitory machine-readable storage medium, including instructions configured to cause one or more data processors to perform actions including:
 defining one or more modules within a biological system based on corresponding biological functions;   defining a set of reactions for the one or more modules within the biological system, wherein the set of reactions indicate how various molecules are consumed and produced through at least a portion of a life cycle of the biological system, and wherein each reaction of the set of reactions identifies stoichiometry indicative of one or more metabolites that are consumed, one or more metabolites that are produced and, for each consumed and produced metabolite, a coefficient indicating a relative amount that is consumed or produced;   identifying one or more additional constraints for the set of reactions;   defining an objective function for the set of reactions based on the stoichiometries of the set of reactions; and   executing a simulation using the set of reactions, the one or more additional constraints, and the objective function to generate the metabolite time course data for a given time point.   
     
     
         16 . The computer-program product of  claim 15 , wherein the actions further include:
 determining an availability value for each metabolite related to the set of reactions, wherein executing the simulation includes determining, for each reaction of the set of reactions, a flux of the reaction based on the availability values, the one or more additional constraints, and the objective function; and   updating a centralized availability value for each metabolite based on the identified fluxes.   
     
     
         17 . The computer-program product of  claim 16 , wherein the fluxes indicate a number of times that each reaction of the set of reactions were performed in the simulation in accordance with the availability values, the one or more additional constraints, and the objective function. 
     
     
         18 . The computer-program product of  claim 15 , wherein the set of reactions further identify one or more enzymes, one or more cofactors, one or more characteristics that are required for a reaction to occur, one or more characteristics that affects a probability of the reaction occurring, one or more properties of the reaction, or any combination thereof. 
     
     
         19 . The computer-program product of  claim 15 , wherein the one or more additional constraints include a flux lower bound and/or a flux upper bound to limit a flux, a quantity of a consumed or produced metabolite, a kinetic constant, a rate of production or decay of a component, an enzyme concentration or activity, a compartment size, a concentration of an external metabolite, or any combination thereof. 
     
     
         20 . The computer-program product of  claim 15 , wherein the actions further include, for a subsequent time point:
 identifying one or more additional constraints for the set of reactions;   defining an objective function for the set of reactions based on the stoichiometries of the set of reactions; and   executing a simulation using the set of reactions, the one or more additional constraints, and the objective function to generate the metabolite time course data for the subsequent time point.