Information processing method for evaluating biochemical pathway models using clinical data
First Claim
1. A method of evaluating a biochemical pathways models using clinical data, comprising the steps of:
- (a) representing the biological model within a computing system, in the form of a hierarchy of Petri nets or stochastic activity nets, wherein the nodes of the net represent biological or biochemical components, and the arcs correspond to the flow of biochemical components in the model;
(b) recording a time series of measurements of some of the biochemical components described by the model, wherein these measurements are made on samples from one or more humans or other living organisms;
(c) storing those observations as a data set in the computing system, which performs the subsequent steps as automated computations;
(d) for each time series in the stored data set, calculating the rate of change of some or all variables with respect to time, and augmenting the data set with that information;
(e) for each input to a network node, labeling the input with the expected effect of an increase in token flow at the input on each output of the node, either “
increasing”
or “
decreasing”
;
(f) comparing an observed pattern of increases and decreases of measured biochemical levels versus the expected pattern of increases and decreases in flow rates of tokens through the corresponding nodes; and
(h) marking the biochemical components for which the expected effect is an increase while the biochemical measurements show a decrease, or vice versa, wherein the marking indicates that the model does not describe the behavior of those biochemical components.
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Abstract
A method of evaluating a biochemical pathways models using clinical data, includes representing the biological model within a computing system, in the form of a hierarchy of Petri nets or stochastic activity nets, wherein the nodes of the net represent biological or biochemical components, and the arcs correspond to the flow of biochemical components in the model. A time series of measurements of some of the biochemical components described by the model are recorded and an observed pattern of relationships between inputs and outputs of the respective nodes is compared to an expected pattern of the relationships to determine whether the model describes the behavior of the biochemical components.
80 Citations
10 Claims
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1. A method of evaluating a biochemical pathways models using clinical data, comprising the steps of:
-
(a) representing the biological model within a computing system, in the form of a hierarchy of Petri nets or stochastic activity nets, wherein the nodes of the net represent biological or biochemical components, and the arcs correspond to the flow of biochemical components in the model;
(b) recording a time series of measurements of some of the biochemical components described by the model, wherein these measurements are made on samples from one or more humans or other living organisms;
(c) storing those observations as a data set in the computing system, which performs the subsequent steps as automated computations;
(d) for each time series in the stored data set, calculating the rate of change of some or all variables with respect to time, and augmenting the data set with that information;
(e) for each input to a network node, labeling the input with the expected effect of an increase in token flow at the input on each output of the node, either “
increasing”
or “
decreasing”
;
(f) comparing an observed pattern of increases and decreases of measured biochemical levels versus the expected pattern of increases and decreases in flow rates of tokens through the corresponding nodes; and
(h) marking the biochemical components for which the expected effect is an increase while the biochemical measurements show a decrease, or vice versa, wherein the marking indicates that the model does not describe the behavior of those biochemical components. - View Dependent Claims (2, 3, 4)
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5. A method of evaluating a biological model comprising the steps of:
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(a) representing the biological model within a computing system, in the form of a hierarchy of Petri nets or stochastic activity nets, wherein the nodes of the net represent biological or biochemical components, and the arcs correspond to the flow of biochemical components in the model;
(b) recording a set of measurements of some of the biochemical components described by the model, wherein these measurements are made on samples from one or more humans or other living organism patients, wherein the set of patients is divided into subsets representing patients with a disease, various diseases, and/or healthy patients;
(c) storing the measurements a data set in the computing system, which performs the subsequent steps as automated computations;
(d) for subsets of the data, calculating the change of some or all measured variables with respect to the corresponding value of that variable for healthy patients or diseased patients in a different subsets, and augmenting the data set with that information;
(e) for each input to a network node, labeling the input with the expected effect of an increase in token flow at the input on each output of the node, either “
increasing”
or “
decreasing”
;
(f) comparing the pattern of increases and decreases of measured biochemical levels in various disease states versus the expected pattern of increases and decreases in flow rates of tokens through the corresponding nodes; and
(g) marking the biochemical components for which the expected effect is an increase while the biochemical measurements show a decrease, or vice versa, the marking indicating that the model does not adequately describe the behavior of those biochemical components. - View Dependent Claims (6, 7, 8, 9, 10)
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Specification