Characterizing biological stimuli by response curves
First Claim
1. A method of classifying a stimulus based on its associated stimulus response path in biological feature space, the method comprising:
- (a) applying a stimulus to cells;
(b) imaging the cells;
(c) deriving two or more stimulus response oaths from images of the cells;
(d) aligning two or more of the stimulus response paths on a common radius, r, from a point in biological feature space where a negative control is applied;
(e) calculating a separation distance, D, between points on two of the stimulus response paths having the common radius, r, from the negative control point; and
(f) classifying the stimulus of at least one of the stimulus response paths on the basis of the calculated value of the separation distance, D, and providing that classification for a user.
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Abstract
A method for calculating distances between stimulus response curves (e.g., dose response curves) allows classification of stimuli. The response curves show how the phenotype of one or more cells changes in response to varying levels of the stimulus. Each “point” on the curve represents quantitative phenotype or signature for cell(s) at a particular level of stimulus (e.g., dose of a therapeutic). The signatures are multivariate phenotypic representations of the cell(s). They include various features of the cell(s) obtained by image analysis. To facilitate the comparison of stimuli, distances between points on the response curves are calculated. First, the response curves may be aligned on a coordinate representing a separate distance, r, from a common point of negative control (e.g., the point where no stimulus is applied). Integration on r may be used to compute the distance between two response curves. The distance between response curves is used to classify stimuli.
66 Citations
16 Claims
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1. A method of classifying a stimulus based on its associated stimulus response path in biological feature space, the method comprising:
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(a) applying a stimulus to cells; (b) imaging the cells; (c) deriving two or more stimulus response oaths from images of the cells; (d) aligning two or more of the stimulus response paths on a common radius, r, from a point in biological feature space where a negative control is applied; (e) calculating a separation distance, D, between points on two of the stimulus response paths having the common radius, r, from the negative control point; and (f) classifying the stimulus of at least one of the stimulus response paths on the basis of the calculated value of the separation distance, D, and providing that classification for a user. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A computer program product comprising a machine readable medium on which is provided program instructions for classifying a stimulus based on its associated stimulus response path in biological feature space, the instructions comprising:
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(a) applying a stimulus to cells; (b) imaging the cells; (c) deriving two or more stimulus response paths from images of the cells; (d) aligning two or more of the stimulus response paths on a common radius, r, from a point in biological feature space where a negative control is applied; (e) calculating a separation distance, D, between points on two of the stimulus response paths having the common radius, r, from the negative control point; and (f) classifying the stimulus of at least one of the stimulus response paths on the basis of the calculated value of the separation distance, D, and providing that classification for a user. - View Dependent Claims (12, 13, 14, 15, 16)
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Specification