Modeling and evaluation metabolic reaction pathways and culturing cells
First Claim
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1. A method for evaluating at least one metabolic pathway and culturing cells, the method comprising:
- generating a symbolic model that represents a network comprising chemical reactions of the at least one metabolic pathway;
evaluating the symbolic model to identify a first set of precursor substrates and/or chemical reactions that are sufficient to produce a set of target products or a second set of precursor substrates and/or chemical reactions that are insufficient to produce the set of target products, wherein the symbolic model comprises a Boolean function that returns a predetermined value if the set of target compounds is produced; and
culturing cells in a medium selected based upon identification of one of the first and second sets to selectively support viability of the cells.
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Abstract
Biological and chemical systems are represented as a symbolic model. Minimal sets of elements of the system are identified from the model, for example, by automatic inference. The model can be constructed from Boolean propositions that are mapped to a binary decision diagram. The model can also be probed using a branch and bound algorithm.
28 Citations
26 Claims
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1. A method for evaluating at least one metabolic pathway and culturing cells, the method comprising:
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generating a symbolic model that represents a network comprising chemical reactions of the at least one metabolic pathway; evaluating the symbolic model to identify a first set of precursor substrates and/or chemical reactions that are sufficient to produce a set of target products or a second set of precursor substrates and/or chemical reactions that are insufficient to produce the set of target products, wherein the symbolic model comprises a Boolean function that returns a predetermined value if the set of target compounds is produced; and culturing cells in a medium selected based upon identification of one of the first and second sets to selectively support viability of the cells. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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10. A method for evaluating at least one metabolic pathway and culturing cells, the method comprising:
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representing a network of chemical reactions of the at least one metabolic pathway as a symbolic model, the model comprising elements that include compounds comprising at least substrates and products, and reactant-product relationships between compounds; determining a Boolean function from the symbolic model, wherein the Boolean function returns a predetermined value if the network produces a set of target products; evaluating the Boolean function to identify a first set of precursor substrates and/or reactant-product relationships that is sufficient to produce the set of target products and/or a second set of precursor substrates and/or reactant-product relationships that is insufficient to produce the set of target products; and culturing cells in a medium selected based upon identification of at least one of the first and second sets to selectively support viability of the cells. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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21. A method for evaluating at least one metabolic pathway and culturing cells, the method comprising:
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inferring a Boolean function from a chemical reaction network of the at least one metabolic pathway that includes relationships between compounds comprising at least substrates and products, the relationships representing chemical reactions between the compounds including precursor substrates and target products, wherein the Boolean function depends on variables, where each variable indicates a presence of at least one of the precursor substrates, and the Boolean function returns a predetermined value for every case in which at least one of the target products is formed from at least one of the precursor substrates; evaluating the Boolean function to identify a first set of precursor substrates and/or relationships that is sufficient to produce a set of target products and/or a second set of precursor substrates and/or relationships that is insufficient to produce the set of target products; and culturing cells in a medium selected based upon identification of at least one of the first and second sets to selectively support viability of the cells. - View Dependent Claims (22, 23, 24, 25, 26)
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Specification