Cytokinetics, Inc.

Daniel A Coleman

Eugeni Vaisberg

Vadim Kutsyy

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.

Characterizing biological stimuli by response curves

Image analysis methods and apparatus are used for determination of the ploidy of cells. The methods may involve segmenting an image to identify one or more discrete regions occupied by cells or nuclei, determining the presence of a particular ploidy indicator feature within the region(s), and providing a value of the indicator feature to a model that classifies cells' ploidy on the basis of the indicator feature. In some embodiments, the indicator feature is a level of DNA in a cell. In certain embodiments, the method further comprises treating one or more cells with a marker that highlights the ploidy indicator feature. In certain embodiments, the cells are treated prior to producing one or more images of the one or more cells. In certain embodiments, the ploidy indicator feature comprises DNA and the marker co-locates with DNA and provides a signal that is captured in the image. In certain embodiments, the signal comprises a fluorescent emission.

Ploidy classification method

Image analysis methods analyze images of cells and place the cells in particular cell cycle phases based upon certain features extracted from the images. The methods can also quantify the total amount of DNA in a cell based on specific features such as fluorescence intensity from fluorescent molecules that bind to DNA. Further, the methods can characterize a cell as mitotic or interphase based on chosen parameters such as the variance in intensity observed in a cell image and/or the size of a region containing DNA. In one example, image analysis methods can classify the cell into one of the following five phases: G, S, G, telophase, and an early stage mitotic phase comprised of prophase, metaphase, and anaphase.

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San Mateo, CA, United States of America

Daniel A Coleman