BACKGROUND

Field of Art

This description generally relates to matching a rate of production of a set of inputs to a downstream rate of demand, and in particular to modifying an objective function of a flux balance analysis representation of the production network.

Description of the Related Art

A cell's metabolism can be represented as a set of linked reaction pathways between molecules, in which the stoichiometric coefficients of reactions function as constraints on the metabolic system's ability to generate the products of metabolism. The stoichiometric coefficients can be used as constraints in a flux balance analysis (FBA) representation of metabolism. FBA is solved for a steady state behavior of the metabolic system, producing a set of input and output fluxes at the boundaries of the metabolic system. The input flux values represent rates at which metabolism takes in reactants, while the output flux values represent rates at which metabolism supplies products.

Under conventional “pure” FBA, one assumes that the behavior modeled by FBA is a closed system, such that production and consumption of every molecule is internal to the metabolic network. Thus in conventional FBA, production matches consumption exactly, leading to a strict mass balance requirement between molecule input and output fluxes. However, pure FBA metabolism does not contain obvious control points from which to adjust production to any actual demand outside of FBA. This problem is compounded by the fact that pure FBA is time independent, such that the flux values are solved for in a single, one-time calculation, preventing time-dependent adjustment of pure FBA production to meet external demand. Conventional solutions to adjusting FBA include artificially limiting the inputs of metabolism, however this does not provide a way to match the metabolic rate to the actual demand within the cell, as reflected in the multiple sub units of the whole cell model.

SUMMARY

A production network integrates FBA metabolism with a plurality of sub-units, each of which contains its own production and consumption of molecules. Sub-units represent biological processes external to metabolism. The production of molecules within FBA metabolism is regulated by the production of inputs to metabolism within upstream sub-units, as well as the consumption of the outputs of metabolism within downstream sub-units of the production network. An objective function of FBA metabolism is modified to reflect upstream supply, downstream demand, and the existing molecule concentrations within the production network. A time series solution of the production network iteratively solves FBA metabolism with new initial conditions produced at each time step.

A method for simulating an outcome of a cell process includes receiving an initial state dataset based on initial net demand for a plurality of molecules in a plurality of sub-units representing production and consumption of molecules external to an FBA system. The method includes calculating an initial solution flux dataset by evaluating the FBA system based on a stoichiometric matrix and an objective function limited by the initial state dataset. The method includes receiving a subsequent net demand for the plurality of molecules from initial solutions to the plurality of sub-units. A subsequent state dataset is calculated based on the initial state dataset, the initial solution flux dataset and the subsequent net demand. A subsequent solution flux dataset is calculated by evaluating the FBA system with an updated objective function limited by the subsequent state dataset. An outcome of the cell process is determined, including calculating a difference between the subsequent solution flux dataset and the initial solution flux dataset.

