Quantification of the Effects of Perturbations on Biological Samples
First Claim
1. A method of profiling the effect of a perturbation relative to the effect of another perturbation on biological samples, comprising:
- subjecting each of at least first and second biological samples to a perturbation;
extracting multiple numerical features from the at least first and second biological samples after perturbation;
classifying the multiple numerical features extracted from each perturbed biological sample using a multivariate classification algorithm;
determining a multivariate profile of the effect a perturbation relative to the effect of another perturbation from the multivariate classification.
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Abstract
A multivariate, automated and scalable method for extracting profiles from images to quantify the effects of perturbations on biological samples. Morphological features are determined from images of treated (perturbed) and control (unperturbed) biological samples, and multivariate classification, for example, using a separating decision hyperplane, is used to separate the distribution of measured feature data into control and treated groups. This classification may be used to determine a magnitude of the effect of the particular perturbation under study. A practical application is high-throughput image-based drug screening, wherein the effects of many different compounds, each applied at different doses and for different exposure times, may be profiled to, for example, characterize compound activities and to identify dose-dependent multiphasic drug responses, or to determine and classify the biological effects of new compounds.
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Citations
54 Claims
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1. A method of profiling the effect of a perturbation relative to the effect of another perturbation on biological samples, comprising:
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subjecting each of at least first and second biological samples to a perturbation; extracting multiple numerical features from the at least first and second biological samples after perturbation; classifying the multiple numerical features extracted from each perturbed biological sample using a multivariate classification algorithm; determining a multivariate profile of the effect a perturbation relative to the effect of another perturbation from the multivariate classification. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18)
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19. A method of profiling the effect of a perturbation at a plurality of levels relative to the effect of a reference perturbation on biological samples, comprising:
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subjecting a plurality of biological samples to a plurality of levels of a perturbation to produce a plurality of perturbed biological samples; subjecting a biological sample to a reference perturbation to produce a reference perturbed biological sample; extracting multiple numerical features from each of the perturbed biological samples; classifying the multiple numerical features extracted from each perturbed biological sample using a multivariate classification algorithm; and determining a plurality of multivariate profiles from the multivariate classification. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36)
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37. A method of profiling an effect on cells of a plurality of perturbations each at a plurality of levels relative to the effect of a reference perturbation, comprising:
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subjecting a plurality of populations of cells to a plurality of perturbations each at a plurality of levels to produce a plurality of perturbed cell populations; subjecting a population of cells to a reference perturbation to produce a reference perturbed cell population; extracting multiple numerical features from each of the perturbed cell populations; determining a plurality of separating hyperplanes, each being between the features extracted from a respective perturbed cell population and features extracted from the reference perturbed cell population; determining a normal vector and classification accuracy score for each hyperplane; and determining a plurality of multivariate profiles from the normal vectors. - View Dependent Claims (38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54)
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Specification