Compositions and methods for modeling bacillus subtilis metabolism
First Claim
1. A computer readable medium or media, comprising:
- (a) a data structure relating a plurality of Bacillus subtilis reactants to a plurality of Bacillus subtilis reactions, wherein each of said Bacillus subtilis reactions comprises a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product, wherein at least one of said Bacillus subtilis reactions is annotated to indicate an associated gene;
(b) a gene database comprising information characterizing said associated gene;
(c) a constraint set for said plurality of Bacillus subtilis reactions, and (d) commands for determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said data representation, wherein said at least one flux distribution is predictive of a Bacillus subtilis physiological function.
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Abstract
The invention provides an in silico model for determining a Bacillus subtilis physiological function. The model includes a data structure relating a plurality of B. subtilis reactants to a plurality of B. subtilis reactions, a constraint set for the plurality of B. subtilis reactions, and commands for determining a distribution of flux through the reactions that is predictive of a B. subtilis physiological function. A model of the invention can further include a gene database containing information characterizing the associated gene or genes. A regulated B. subtilis reaction can be represented in a model of the invention by including a variable constraint for the regulated reaction. The invention further provides methods for making an in silico B. subtilis model and methods for determining a B. subtilis physiological function using a model of the invention.
201 Citations
66 Claims
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1. A computer readable medium or media, comprising:
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(a) a data structure relating a plurality of Bacillus subtilis reactants to a plurality of Bacillus subtilis reactions, wherein each of said Bacillus subtilis reactions comprises a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product, wherein at least one of said Bacillus subtilis reactions is annotated to indicate an associated gene;
(b) a gene database comprising information characterizing said associated gene;
(c) a constraint set for said plurality of Bacillus subtilis reactions, and (d) commands for determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said data representation, wherein said at least one flux distribution is predictive of a Bacillus subtilis physiological function. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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13. A computer readable medium or media, comprising:
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(a) a data structure relating a plurality of Bacillus subtilis reactants to a plurality of Bacillus subtilis reactions, wherein each of said Bacillus subtilis reactions comprises a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate-and said product, wherein at least one of said Bacillus subtilis reactions is a regulated reaction;
(b) a constraint set for said plurality of Bacillus subtilis reactions, wherein said constraint set includes a variable constraint for said regulated reaction, and (c) commands for determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said data representation, wherein said at least one flux distribution is predictive of a Bacillus subtilis physiological function. - View Dependent Claims (14, 15, 16, 17, 18, 19)
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20. A computer readable medium or media, comprising:
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(a) a data structure relating a plurality of Bacillus subtilis reactants to a plurality of Bacillus subtilis reactions, wherein each of said Bacillus subtilis reactions comprises a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product;
(b) a constraint set for said plurality of Bacillus subtilis reactions, and (c) commands for determining at least one flux distribution that minimizes or maximizes an objective function when said constraint set is applied to said data representation, wherein said at least one flux distribution is predictive of Bacillus subtilis growth.
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21. A method for predicting a Bacillus subtilis physiological function, comprising:
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(a) providing a data structure relating a plurality of Bacillus subtilis reactants to a plurality of Bacillus subtilis reactions, wherein each of said Bacillus subtilis reactions comprises a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product, wherein at least one of said Bacillus subtilis reactions is annotated to indicate an associated gene;
(b) providing a constraint set for said plurality of Bacillus subtilis reactions;
(c) providing an objective function, and (d) determining at least one flux distribution that minimizes or maximizes said objective function when said constraint set is applied to said data structure, thereby predicting a Bacillus subtilis physiological function related to said gene. - View Dependent Claims (22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44)
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45. A method for predicting a Bacillus subtilis physiological function, comprising:
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(a) providing a data structure relating a plurality of Bacillus subtilis reactants to a plurality of Bacillus subtilis reactions, wherein each of said Bacillus subtilis reactions comprises a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product, wherein at least one of said Bacillus subtilis reactions is a regulated reaction;
(b) providing a constraint set for said plurality of Bacillus subtilis reactions, wherein said constraint set includes a variable constraint for said regulated reaction;
(c) providing a condition-dependent value to said variable constraint;
(d) providing an objective function, and (e) determining at least one flux distribution that minimizes or maximizes said objective function when said constraint set is applied to said data structure, thereby predicting a Bacillus subtilis physiological function. - View Dependent Claims (46, 47, 48, 49, 50, 51)
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52. A method for predicting Bacillus subtilis growth, comprising:
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(a) providing a data structure relating a plurality of Bacillus subtilis reactants to a plurality of Bacillus subtilis reactions, wherein each of said Bacillus subtilis reactions comprises a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product;
(b) providing a constraint set for said plurality of Bacillus subtilis reactions;
(c) providing an objective function, and (d) determining at least one flux distribution that minimizes or maximizes said objective function when said constraint set is applied to said data structure, thereby predicting Bacillus subtilis growth.
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53. A method for making a data structure relating a plurality of Bacillus subtilis reactants to a plurality of Bacillus subtilis reactions in a computer readable medium or media, comprising:
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(a) identifying a plurality of Bacillus subtilis reactions and a plurality of Bacillus subtilis reactants that are substrates and products of said Bacillus subtilis reactions;
(b) relating said plurality of Bacillus subtilis reactants to said plurality of Bacillus subtilis reactions in a data structure, wherein each of said Bacillus subtilis reactions comprises a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product;
(c) determining a constraint set for said plurality of Bacillus subtilis reactions;
(d) providing an objective function;
(e) determining at least one flux distribution that minimizes or maximizes said objective function when said constraint set is applied to said data structure, and (f) if said at least one flux distribution is not predictive of a Bacillus subtilis physiological function, then adding a reaction to or deleting a reaction from said data structure and repeating step (e), if said at least one flux distribution is predictive of a Bacillus subtilis physiological function, then storing said data structure in a computer readable medium or media. - View Dependent Claims (54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65)
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66. A data structure relating a plurality of Bacillus subtilis reactants to a plurality of Bacillus subtilis reactions, wherein said data structure is produced by a process comprising:
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(a) identifying a plurality of Bacillus subtilis reactions and a plurality of Bacillus subtilis reactants that are substrates and products of said Bacillus subtilis reactions;
(b) relating said plurality of Bacillus subtilis reactants to said plurality of Bacillus subtilis reactions in a data structure, wherein each of said Bacillus subtilis reactions comprises a reactant identified as a substrate of the reaction, a reactant identified as a product of the reaction and a stoichiometric coefficient relating said substrate and said product;
(c) determining a constraint set for said plurality of Bacillus subtilis reactions;
(d) providing an objective function;
(e) determining at least one flux distribution that minimizes or maximizes said objective function when said constraint set is applied to said data structure, and (f) if said at least one flux distribution is not predictive of Bacillus subtilis physiology, then adding a reaction to or deleting a reaction from said data structure and repeating step (e), if said at least one flux distribution is predictive of Bacillus subtilis physiology, then storing said data structure in a computer readable medium or media.
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Specification