Metabolic phenotyping
First Claim
1. A method of generating models with which to characterise selected aspects of a metabolic phenotype of subjects without dosing a test substance to those subjects or with which to predict, without dosing, the post-dose responses of subjects where those responses are dependent on metabolic phenotype, the method comprising:
- obtaining pre-dose data relating to a plurality of subjects before dosing with a dosing substance;
obtaining post-dose data relating to the plurality of subjects after dosing with the dosing substance; and
correlating inter-subject variation in the pre-dose data with inter-subject variation in the post-dose data, and generating a pre-to-post-dose predictive model on the basis of the observed correlation.
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Abstract
A method of generating models with which to characterise selected aspects of the metabolic phenotype of subjects without dosing a test substance to those subjects or with which to predict, without dosing, the post-dose responses of subjects where those responses are dependent on metabolic phenotype, the method comprising: obtaining pre-dose data relating to a plurality of subjects before dosing with a dosing substance; obtaining post-dose data relating to the plurality of subjects after dosing with the dosing substance; and correlating inter-subject variation in the pre-dose data with inter-subject variation in the post-dose data, and generating a pre-to-post-dose predictive model on the basis of the observed correlation. The models may be used to determine selected aspects of the metabolic phenotype of a subject or to predict, without dosing, the post-dose responses of subjects. This is achieved by analysing data relating to the un-dosed subject in relation to a model describing the correlation of pre-dose and post-dose data relating to a plurality of subjects when dosed with a particular substance which challenges the biochemical transformation or pathway of interest; and generating, according to the predetermined criteria of the model, a numerical measure or classification describing the metabolic phenotype of the un-dosed subject.
42 Citations
58 Claims
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1. A method of generating models with which to characterise selected aspects of a metabolic phenotype of subjects without dosing a test substance to those subjects or with which to predict, without dosing, the post-dose responses of subjects where those responses are dependent on metabolic phenotype, the method comprising:
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obtaining pre-dose data relating to a plurality of subjects before dosing with a dosing substance;
obtaining post-dose data relating to the plurality of subjects after dosing with the dosing substance; and
correlating inter-subject variation in the pre-dose data with inter-subject variation in the post-dose data, and generating a pre-to-post-dose predictive model on the basis of the observed correlation. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 29, 30, 31, 32, 33, 35, 36, 37, 38, 40, 41, 42, 43, 44, 45, 46, 47, 49, 50, 51, 52, 53, 55, 56, 57, 58)
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17. A method of determining selected aspects of the metabolic phenotype of a subject, the method comprising:
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analysing data relating to an un-dosed subject in relation to a model describing the correlation of pre-dose and post-dose data relating to a plurality of subjects dosed with a particular substance which challenges the biochemical transformation or pathway of interest;
generating, according to a predetermined criteria of the model, a numerical measure or classification describing the metabolic phenotype of the un-dosed subject. - View Dependent Claims (18, 19, 20)
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21. A method of predicting a reaction of a subject to a dosing substance, the method comprising:
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analysing data relating to an un-dosed subject in relation to a model characterising the correlation of pre-dose and post-dose data relating to a plurality of subjects dosed with the particular dosing substance; and
generating, according to the predetermined criteria of the model, a numerical or class prediction for the expected response of the un-dosed subject if it were to be dosed with the dosing substance. - View Dependent Claims (22, 23, 24, 25, 26, 27, 28, 34, 39, 54)
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48. Apparatus for response prediction and/or for metabolic phenotyping, the apparatus comprising:
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one or more models, each model modelling the correlation of pre-dose and post-dose data relating to a plurality of subjects dosed with a particular dosing substance;
a processor for analysing data relating to an un-dosed subject in relation to at least one of the models and thereby determining one or more aspects of the metabolic phenotype of the un-dosed subject or predicting its responses to dosing according to the model(s) employed.
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Specification