Mode of action screening method
AssigneeRigel Pharmaceuticals, Inc.
InventorsJohn McLaughlin, Zachary Pincus, Jim Bernstein
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Abstract
Certain aspects of this disclosure relate to a screening method. In general terms, the screening assay comprises contacting test cells with a test compound to provide contacted test cells, obtaining values for a plurality of cytological attributes of the contacted test cells, and scoring the cells using the values to provide a likelihood score for at least one of a plurality of classifiers, where the plurality of classifiers are defined using values for cytological attributes obtained from cells that have been contacted with compounds of known mode of action.
Claims20
A screening method comprising:
- a) contacting a population of test cells with a test compound to provide contacted test cells;
- b) obtaining values for a plurality of cytological attributes of said contacted test cells;
- c) determining whether the phenotype of the test cells matches the phenotype of cells that have been treated with a compound having known mode of action, wherein the determining is done by:
- (i) obtaining a set of classifiers for a plurality of compounds of known mode of action, wherein the classifiers are defined using values for said cytological attributes obtained from cells that have been contacted with compounds of known mode of action;
- and
- (ii) calculating a likelihood score indicating the likelihood that the values obtained for the contacted cells match a classifier of the set of classifiers,
- wherein an increased likelihood score increases the confidence that the phenotype of the test cells matches the phenotype of cells that have been treated with a compound having known mode of action, and
- d) identifying the test compound as having a desired mode of action, wherein said test compound has a profile of likelihood scores that is similar to that of a compound of known mode of action.
A microscopy system comprising:
- a) a device for capturing an image of a population of cells;
- and
- b) a computer, operably linked to said device, comprising programming for:
- i. analyzing said image to provide values for a plurality of cytological attributes of said cells;
- and
- ii. scoring said cells using said values to provide a likelihood score for at least one of a set of classifiers,
- wherein said set classifiers are defined using values for said cytological attributes obtained from cells that have been contacted with compounds of known mode of action and wherein the likelihood score indicates the likelihood that the values of (b)(i) match a classifier of the set of classifiers.
A method for standardizing an image of cells that are grown in a well of a multi-well culture plate, comprising:
- a) subtracting the median background pixel value of a first image of cells that are:
- i. present in a first well of said multi-well plate;
- and
- ii. contacted with a test agent,
- from the pixel values of said first image to provide a second image;
- b) dividing the pixel values of said second image by the median foreground pixel values of untreated cells in a second well of said multi-well plate, thereby providing a third image.
A method for providing a phenotypic classifier, comprising:
- a) contacting a first population of cells with a first compound having a first known mode of action to provide a first population of contacted cells;
- and
- b) contacting a second population of cells with a second compound having a second known mode of action to provide a second population of contacted cells;
- c) obtaining values for a plurality of cytological attributes of:
- i. said first population of contacted cells,
- ii. said second population of contacted cells, and
- iii. an untreated population of cells, and
- d) identifying ranges of values for each of said cytological attributes that, together, distinguish said first population of contacted cells from said second population of contacted cells and said untreated population of cells.
Dependencies are inferred from the claim text.