Predicting hepatotoxicity using cell based assays
First Claim
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1. A method of determining whether a stimulus induces a hepatotoxic response or a pathology, the method comprising:
- (a) receiving one or more images of hepatocytes that have been exposed to a stimulus;
(b) from the images, automatically generating a plurality features characterizing the hepatocytes; and
(c) applying the plurality of features to a hepatotoxicity model or a pathology model to thereby classify the stimulus as to hepatotoxicity or pathology.
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Abstract
Cell based assays are used to assess the hepatotoxicity of a stimulus. Imaging technologies are used to analyze the effects of a stimulus on hepatocytes. Image analysis may characterize the stimulus on the basis of whether it is hepatotoxic, and if so what type of pathology is exhibited; e.g., apoptosis, necrosis, cholestasis, and/or steatosis.
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Citations
23 Claims
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1. A method of determining whether a stimulus induces a hepatotoxic response or a pathology, the method comprising:
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(a) receiving one or more images of hepatocytes that have been exposed to a stimulus;
(b) from the images, automatically generating a plurality features characterizing the hepatocytes; and
(c) applying the plurality of features to a hepatotoxicity model or a pathology model to thereby classify the stimulus as to hepatotoxicity or pathology. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 17, 18, 19)
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9. A method of generating a hepatotoxicity model or pathology model for determining whether a stimulus induces a hepatotoxic response or a pathology, the method comprising:
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(a) receiving a training set for generating the hepatotoxicity or pathology model, wherein the training set comprises phenotypic information for various stimuli some of which are known to induce hepatotoxic responses or pathology responses and others which are known to not induce hepatotoxic or pathology responses, wherein the phenotypic information for each stimulus comprises a plurality of features derived from images of the hepatocytes exposed to said stimuli; and
(b) from the training set, generating the hepatotoxicity model or pathology model for classifying stimuli as to hepatotoxicity or pathology based on at least some of the plurality of features obtained from hepatocytes treated with a stimulus to be classified by the hepatotoxicity model or pathology model. - View Dependent Claims (10, 11, 12)
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13. A computer program product comprising a machine readable medium on which is provided program instructions for determining whether a stimulus induces a hepatotoxic response or a pathology, the program instructions comprising:
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(a) code for receiving one or more images of hepatocytes that have been exposed to a stimulus;
(b) code for automatically generating, from the images, a plurality features characterizing the hepatocytes; and
(c) code for applying the plurality of features to a hepatotoxicity model or pathology model to thereby classify the stimulus as to hepatotoxicity or pathology. - View Dependent Claims (14, 15, 16)
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20. A computer program product comprising a machine readable medium on which is provide program instructions for generating a hepatotoxicity model or pathology model for determining whether a stimulus induces a hepatotoxic response or a pathology, the program instructions comprising:
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(a) code for receiving a training set for generating the hepatotoxicity or pathology model, wherein the training set comprises phenotypic information for various stimuli some of which are known to induce hepatotoxic responses or pathology responses and others which are known to not induce hepatotoxic or pathology responses, wherein the phenotypic information for each stimulus comprises a plurality of features derived from images of the hepatocytes exposed to said stimuli; and
(b) code for generating, from the training set, the hepatotoxicity model or pathology model for classifying stimuli as to hepatotoxicity or pathology based on at least some of the plurality of features obtained from hepatocytes treated with a stimulus to be classified by the hepatotoxicity model or pathology model. - View Dependent Claims (21, 22, 23)
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Specification