Modified fba in a production network

Abstract

A method for matching production of FBA metabolism to supply and demand within a larger production network is described herein. An objective function of FBA metabolism is modified to include an upstream supply generated in upstream sub-units, as well as a downstream demand generated within downstream sub-units in the production network. FBA metabolism and the upstream and downstream sub-units are iteratively solved with updated initial conditions, producing a time series solution to the production network.

What is claimed is: 
     
         1 . A method comprising:
 receiving an initial state dataset, the initial state dataset including information representing an initial concentration of at least one molecule within an existing cellular environment of at least one biological cell and information representing an initial net demand for at least one molecule in a plurality of sub-units, wherein the plurality of sub-units represent a plurality of biological processes external to a metabolism of the at least one biological cell;   calculating a first flux dataset based on a model and an objective function, wherein the model is configured to model the metabolism of the at least one biological cell, and wherein the objective function is configured based on a stoichiometric matrix and target values derived from the initial net demand;   generating a subsequent state dataset based on the initial state dataset and the first flux dataset, the subsequent state dataset including information representing a simulated concentration of the at least one molecule within the existing cellular environment of the at least one biological cell and information representing a subsequent net demand for the at least one molecule in the plurality of sub-units;   calculating a second flux dataset based on the model and an updated objective function, wherein the updated objective function is configured based on the objective function and target values derived from the subsequent net demand; and   calculating a difference between the first flux dataset and the second flux dataset, the calculated difference representing an outcome of a cell process of the at least one biological cell.   
     
     
         2 . The method of  claim 1 , wherein the initial net demand for the at least one molecule in the plurality of sub-units is determined based on:
 an initial rate of supply in a first sub-unit of the plurality of sub-units, the first sub-unit representing at least one biological process upstream from the metabolism of the at least one biological cell; and   an initial rate of demand in a second sub-unit of the plurality of sub-units, the second sub-unit representing at least one biological process downstream from the metabolism of the at least one biological cell.   
     
     
         3 . The method of  claim 1 , wherein the initial state dataset further includes information representing an initial concentration of at least one molecule within the plurality of sub-units. 
     
     
         4 . The method of  claim 1 , wherein the initial state dataset further includes a set of intrinsic rate parameters, the set of intrinsic rate parameters representing at least one constraint of the metabolism of the at least one biological cell. 
     
     
         5 . The method of  claim 4 , wherein the set of intrinsic rate parameters includes at least one of: a proportional rate limit, an integral rate limit, and a derivative rate limit. 
     
     
         6 . The method of  claim 1 , wherein calculating the first flux dataset based on the model and the objective function comprises subtracting the target values derived from the initial net demand from proportional flux contributions calculated based on a set of flux values. 
     
     
         7 . The method of  claim 1 , wherein calculating the second flux dataset based on the model and the updated objective function comprises subtracting the target values derived from the subsequent net demand from proportional flux contributions calculated based on a set of flux values. 
     
     
         8 . The method of  claim 1 , wherein at least one biological process of the plurality of biological processes corresponds to at least one of transcription, translation, cellular communication, cellular reproduction, and cellular transport. 
     
     
         9 . The method of  claim 1 , wherein:
 first flux dataset and the second flux dataset,   the first flux dataset is associated with a first time;   the second flux dataset is associated with a second time after the first time; and   the difference between the first flux dataset and the second flux dataset represents metabolic production over a time interval between the first time and the second time.   
     
     
         10 . The method of  claim 1 , wherein the outcome of the cell process of the at least one biological cell comprises at least one of a concentration of a molecule within a production network of the at least one biological cell. 
     
     
         11 . A non-transitory computer readable storage medium containing computer program code executable on a processor for causing the processor to perform operations, the operations comprising:
 receiving an initial state dataset, the initial state dataset including information representing an initial concentration of at least one molecule within an existing cellular environment of at least one biological cell and information representing an initial net demand for at least one molecule in a plurality of sub-units, wherein the plurality of sub-units represent a plurality of biological processes external to a metabolism of the at least one biological cell;   calculating a first flux dataset based on a model and an objective function, wherein the model is configured to model the metabolism of the at least one biological cell, and wherein the objective function is configured based on a stoichiometric matrix and target values derived from the initial net demand;   generating a subsequent state dataset based on the initial state dataset and the first flux dataset, the subsequent state dataset including information representing a simulated concentration of the at least one molecule within the existing cellular environment of the at least one biological cell and information representing a subsequent net demand for the at least one molecule in the plurality of sub-units;   calculating a second flux dataset based on the model and an updated objective function, wherein the updated objective function is configured based on the objective function and target values derived from the subsequent net demand; and   calculating a difference between the first flux dataset and the second flux dataset, the calculated difference representing an outcome of a cell process of the at least one biological cell.   
     
     
         12 . The non-transitory computer readable storage medium of  claim 11 , wherein the initial net demand for the at least one molecule in the plurality of sub-units is determined based on:
 an initial rate of supply in a first sub-unit of the plurality of sub-units, the first sub-unit representing at least one biological process upstream from the metabolism of the at least one biological cell; and   an initial rate of demand in a second sub-unit of the plurality of sub-units, the second sub-unit representing at least one biological process downstream from the metabolism of the at least one biological cell.   
     
     
         13 . The non-transitory computer readable storage medium of  claim 11 , wherein the initial state dataset further includes information representing an initial concentration of at least one molecule within the plurality of sub-units. 
     
     
         14 . The non-transitory computer readable storage medium of  claim 11 , wherein the initial state dataset further includes a set of intrinsic rate parameters, the set of intrinsic rate parameters representing at least one constraint of the metabolism of the at least one biological cell. 
     
     
         15 . The non-transitory computer readable storage medium of  claim 14 , wherein the set of intrinsic rate parameters includes at least one of: a proportional rate limit, an integral rate limit, and a derivative rate limit. 
     
     
         16 . The non-transitory computer readable storage medium of  claim 11 , wherein calculating the first flux dataset based on the model and the objective function comprises subtracting the target values derived from the initial net demand from proportional flux contributions calculated based on a set of flux values. 
     
     
         17 . The non-transitory computer readable storage medium of  claim 11 , wherein calculating the second flux dataset based on the model and the updated objective function comprises subtracting the target values derived from the subsequent net demand from proportional flux contributions calculated based on a set of flux values. 
     
     
         18 . The non-transitory computer readable storage medium of  claim 11 , wherein at least one biological process of the plurality of biological processes corresponds to at least one of transcription, translation, cellular communication, cellular reproduction, and cellular transport. 
     
     
         19 . The non-transitory computer readable storage medium of  claim 11 , wherein:
 first flux dataset and the second flux dataset,   the first flux dataset is associated with a first time;   the second flux dataset is associated with a second time after the first time; and   the difference between the first flux dataset and the second flux dataset represents metabolic production over a time interval between the first time and the second time.   
     
     
         20 . The non-transitory computer readable storage medium of  claim 11 , wherein the outcome of the cell process of the at least one biological cell comprises at least one of a concentration of a molecule within a production network of the at least one biological cell.