Interpolated image response
First Claim
1. A method of generating a degree of response scale for a population subject to multiple levels of a perturbation, wherein a response is a representation of the multidimensional state of a population, said method comprising the steps of:
- a) determining a fingerprint of a first sample of said population subjected to a first level of perturbation, thus obtaining a low-response reference fingerprint that is a representation of the multidimensional state of a low-response population;
b) determining a fingerprint of a second sample of said population subjected to a second level of perturbation greater than said first level of perturbation, thus obtaining a high-response reference fingerprint that is a representation of the multidimensional state of a high-response population;
c) determining a set of interpolated fingerprints from said low-response reference fingerprint and said high-response reference fingerprint, wherein each interpolated fingerprint is a representation of the multidimensional state of a population exhibiting a degree of response intermediate to that of the low-response and high-response populations;
wherein said degree of response scale consists of said set of interpolated fingerprints, said low-response reference fingerprint, and said high-response reference fingerprint, each indexed by a corresponding degree of response.
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Abstract
Systems and methods are provided for characterizing a multidimensional distribution of responses from the objects in a populations subject to a perturbation. The methods enable the creation of a “degree of response” scale interpolated from non-perturbed and perturbed reference populations. The methods enables, using the interpolated degree of response scale, the quantitation of a degree of response of a test compound subject to a given level of perturbation, and enables the generation of a dose-response curve for a test compound. The methods are useful in a wide range of applications, such cellular analysis and high-content screening of compounds, as carried out in pharmaceutical research.
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Citations
18 Claims
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1. A method of generating a degree of response scale for a population subject to multiple levels of a perturbation, wherein a response is a representation of the multidimensional state of a population, said method comprising the steps of:
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a) determining a fingerprint of a first sample of said population subjected to a first level of perturbation, thus obtaining a low-response reference fingerprint that is a representation of the multidimensional state of a low-response population;
b) determining a fingerprint of a second sample of said population subjected to a second level of perturbation greater than said first level of perturbation, thus obtaining a high-response reference fingerprint that is a representation of the multidimensional state of a high-response population;
c) determining a set of interpolated fingerprints from said low-response reference fingerprint and said high-response reference fingerprint, wherein each interpolated fingerprint is a representation of the multidimensional state of a population exhibiting a degree of response intermediate to that of the low-response and high-response populations;
wherein said degree of response scale consists of said set of interpolated fingerprints, said low-response reference fingerprint, and said high-response reference fingerprint, each indexed by a corresponding degree of response. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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8. A method of analyzing the response of a test population subjected to a known level of a test perturbation, relative to a reference perturbation, wherein a response is a representation of the multidimensional state of a population, said method comprising the steps of:
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a) determining a degree of response scale by i) determining a fingerprint of a first sample of said population subjected to a first level of said reference perturbation, thus obtaining a low-response reference fingerprint that is a representation of the multidimensional state of a low-response population;
ii) determining a fingerprint of a second sample of said population subjected to a second level of said reference perturbation greater than said first level of perturbation, thus obtaining a high-response reference fingerprint that is a representation of the multidimensional state of a high-response population;
iii) determining a set of interpolated fingerprints from said low-response reference fingerprint and said high-response reference fingerprint, wherein each interpolated fingerprint is a representation of the multidimensional state of a population exhibiting a degree of response intermediate to that of the low-response and high-response populations;
wherein said degree of response scale consists of said set of interpolated fingerprints, said low-response reference fingerprint, and said high-response reference fingerprint, each indexed by a corresponding degree of response;
b) determining a fingerprint of said test population subjected to said known level of a test perturbation, thus obtaining a test fingerprint that is a representation of the multidimensional state of said test population; and
c) determining a degree of response of said test population by determining from among said degree of response scale a fingerprint most similar to said test fingerprint and identifying a degree of response corresponding to said most similar fingerprint. - View Dependent Claims (9, 10, 11, 12, 13, 14, 15, 16, 18)
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17. A method of generating a dose-response relationship for a population subjected to a perturbation, wherein a response is a representation of the multidimensional state of a population, said method comprising the steps of:
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a) determining a degree of response scale by i) determining a fingerprint of a first sample of said population subjected to a first level of perturbation, thus obtaining a low-response reference fingerprint that is a representation of the multidimensional state of a low-response population;
ii) determining a fingerprint of a second sample of said population subjected to a second level of perturbation greater than said first level of perturbation, thus obtaining a high-response reference fingerprint that is a representation of the multidimensional state of a high-response population; and
iii) determining a set of interpolated fingerprints from said low-response reference fingerprint and said high-response reference fingerprint, wherein each interpolated fingerprint is a representation of the multidimensional state of a population exhibiting a degree of response intermediate to that of the low-response and high-response populations;
wherein said degree of response scale consists of said set of interpolated fingerprints, said low-response reference fingerprint, said high-response reference fingerprint, each indexed by a corresponding degree of response;
b) determining a plurality of fingerprints of a plurality of test samples of said population, each subjected a different known level of said test perturbation, thus obtaining a test fingerprint corresponding to each of a plurality of levels of perturbation;
c) determining a degree of response for each test fingerprint by determining from among said degree of response scale a fingerprint most similar to said test fingerprint and identifying a degree of response corresponding to said most similar fingerprint;
wherein said dose-response relationship is represented by said degree of response obtained for each of said plurality of levels of perturbation.
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Specification