Method For Predicting Biological Systems Responses
First Claim
1. A method for predicting the biological systems effects of a test substance comprising:
- a) providing a battery of cells to be treated;
b) incubating the cells with the test substance;
c) acquiring images of cells within the battery;
d) analyzing the images to measure or detect cellular features indicative of cellular functional classes;
e) creating a response profile comprising at least 6 of the cellular features; and
f) comparing the response profile of the test substance to a database of response profiles for substances with known biological systems effects;
wherein the extent of correlation between the response profile of the test substance to the database of response profiles for substances with known biological systems effects indicates the probability that the test substance will exhibit a biological systems effect in a living cell, tissue or organism.
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Abstract
The inventive method employs a “systems biology” approach to predicting biological responses resulting from exposure to the test substance. In one embodiment, the invention provides an automated method for predicting the biological systems effects of a test substance. In another embodiment, the invention provides a method for constructing a knowledgebase (or database) of response profiles for reference substances with known biological systems effects. In another embodiment, the invention provides a set of protocols and software tools used to carry out the profiling. Another embodiment of the invention is a panel of reagents and protocols required for generating response profiles, either to create an knowledgebase, or to use with an existing knowledgebase and informatics software to profile substance physiological effects. Another embodiment of the invention is a database of physiological profiles.
134 Citations
48 Claims
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1. A method for predicting the biological systems effects of a test substance comprising:
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a) providing a battery of cells to be treated; b) incubating the cells with the test substance; c) acquiring images of cells within the battery; d) analyzing the images to measure or detect cellular features indicative of cellular functional classes; e) creating a response profile comprising at least 6 of the cellular features; and f) comparing the response profile of the test substance to a database of response profiles for substances with known biological systems effects;
wherein the extent of correlation between the response profile of the test substance to the database of response profiles for substances with known biological systems effects indicates the probability that the test substance will exhibit a biological systems effect in a living cell, tissue or organism. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41)
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2. A method for constructing a database of response profiles for reference substances with known biological systems effects comprising:
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a) providing a battery of cells to be treated; b) incubating the cells with the a first reference substance; c) acquiring images of cells within the battery; d) analyzing the images to measure or detect cellular features indicative of cellular functional classes; e) creating a response profile comprising at least 6 of the cellular features; f) adding the response profile for the first reference substance to the database; and g) optionally repeating steps a-f substituting a second reference substance for the first reference substance. - View Dependent Claims (48)
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42. A kit comprising one or more reagents and instructions for employing the reagents to assay a battery of cells in accordance with a protocol involving
a) incubating a battery of cells with a test or reference substance; -
b) acquiring images of cells within the battery; c) analyzing the images to measure or detect cellular features d) indicative of cellular functional classes; and e) creating a response profile comprising at least 6 of the cellular features. - View Dependent Claims (43, 44, 45, 46, 47)
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Specification