Modelling of biochemical pathways

A computational method of investigating the effect of a test substance on a biochemical pathway comprising:

• storing a set of mathematical expressions which are effective to calculate values representing pre-selected metabolite concentrations in a pre-selected, reference biochemical pathway from an initial value representing the measured concentration of one metabolite in said reference biochemical pathway
• storing a set of values representing measured concentrations of the metabolites in a second biochemical pathway containing the same metabolites as the reference pathway;
• using said mathematical expressions to calculate a predicted value of concentration of at least one said metabolite in said second biochemical pathway from an initial value representing the measured concentration of one metabolite in said second pathway;
• comparing said predicted values with corresponding values representing measured metabolite concentration to obtain a comparison relationship;
• modifying at least some of the expressions so as to match predicted values calculated therefrom to the values representing measured metabolite concentrations of the second biochemical pathway, thereby providing a set of expressions modelling said second pathway;
• treating a biochemical pathway with at least one test substance to provide a third biochemical pathway containing the same metabolites as the reference and second pathways and thereafter assaying a test sample thereof to measure the concentration of at least one metabolite lying within the third biochemical pathway;
• storing values representing said measured concentrations in said third pathway;
• using said mathematical expressions to calculate a predicted value of concentration of at least one metabolites in the third pathway from a value representing the measured concentration of one other metabolite in said third pathway;
• comparing at least one said predicted value with the corresponding value representing the measured metabolite concentration in said third pathway to obtain a comparison relationship;
• and
• deriving a quality measure of the match between two biochemical pathways on the basis of the comparison relationship.

A method of creating a computational representation of a biochemical pathway comprising a first metabolite and a plurality of further metabolites whose concentrations are directly or indirectly dependent on the concentration of the first metabolite, by steps of

• choosing a set of mathematical expressions for calculating predicted values representing concentrations of said further metabolites from an initial value representing a measured concentration of the first metabolite in an embodiment of the biochemical pathway;
• modifying at least some of the expressions so as to match the calculated values to a set of reference values representing measured concentrations in the embodiment of the biochemical pathway;
• and
• storing the expressions in memory.

A computational method of investigating a biochemical pathway comprising:

• storing a set of values representing measured concentrations of a set of metabolites in a biochemical pathway under investigation;
• calculating a predicted value of concentration of at least one metabolite in said pathway from an initial value representing the measured concentration of one other metabolite in said pathway under investigation;
• comparing one or more predicted values with corresponding values representing the measured metabolite concentrations to obtain a comparison relationship;
• and
• deriving a quality measure of the match between the biochemical pathway under investigation and another biochemical pathway containing these metabolites on the basis of the comparison relationship.

A computational investigative method comprising:

• storing a set of mathematical expressions which are effective to calculate values representing pre-selected metabolite concentrations in a pre-selected, reference biochemical pathway from an initial value representing the measured concentration of one metabolite in said reference biochemical pathway;
• storing a set of values representing measured concentrations of the metabolites in a second biochemical pathway containing the same metabolites as the reference pathway;
• using said mathematical expressions to calculate a predicted value of concentration of at least one said metabolite in said second biochemical pathway from an initial value representing the measured concentration of one metabolite in said second pathway;
• comparing one or more said predicted values with corresponding values representing measured metabolite concentrations to obtain a comparison relationship;
• and
• deriving a quality measure of the match between two biochemical pathways on the basis of the comparison relationship.

A computational investigative method for a biochemical pathway comprising a first metabolite and a plurality of further metabolites whose concentrations are directly or indirectly dependent on the concentration of the first metabolite, comprising steps of

• choosing a set of mathematical expressions for calculating predicted values representing concentrations of said further metabolites from an initial value representing a measured concentration of the first metabolite in a reference biochemical pathway;
• modifying at least some of the expressions so as to match the calculated values to a set of reference values representing measured concentrations in the reference biochemical pathway;
• and
• storing the expressions in memory;
• storing a set of values representing measured concentrations of the metabolites in a second biochemical pathway containing the same metabolites as the reference pathway;
• using said mathematical expressions to calculate predicted values of concentration of a plurality of said metabolites in the second pathway from an initial value representing the measured concentration of one metabolite in said second pathway;
• comparing predicated values with the corresponding values representing measured metabolite concentrations in said second pathway to obtain a comparison relationship;
• and
• deriving a quality measure of the match between said second biochemical pathway and the pre-selected, reference biochemical pathway on the basis of the comparison relationship.

A computer memory product having stored thereon at least one digital file, said memory product comprising computer readable memory and said stored digital file or files constituting a computer program for investigating a biochemical pathway comprising

• (a) code selected from the group consisting of:
• code representing a set of mathematical expressions which are effective to calculate values representing pre-selected concentrations of metabolites in a pre-selected reference biochemical pathway from an initial value representing the measured concentration of one metabolite in said reference biochemical pathway;
• code effective to receive input of and store mathematical expressions, code effective to receive input and store selection from among a collection of stored expressions, and combinations thereof;
• plus
• b) code adapted to perform the following steps when the program is run on a data processing system:
• receive input of and store a set of values representing measured metabolite concentrations in a biochemical pathway;
• use said mathematical expressions to calculate a predicted value of concentration of at least one metabolite in a pathway from an initial value representing the measured concentration of one metabolite in said pathway;
• compare one or more said predicted values with corresponding values representing the measured metabolite concentrations to obtain a comparison relationship;
• derive a quality measure of the match between two biochemical pathways on the basis of the comparison relationship;
• and
• display or output said quality measure.