摘要:
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.
摘要:
Methods, data processing apparatus and computer program products for characterising cells and the affect of treatments administered to cells are disclosed. In particular methods of identifying bi-nuclear cells are described which include capturing an image of a plurality of marked cells and processing image to obtain features of the plurality of cells. The features are analyzed to determine whether the feature is indicative of bi-nuclear cells. Those cells for which the first feature is indicative of bi-nuclear cells are identified as being bi-nuclear. Three algorithms in particular are described. A first algorithm can be used to determine the number of nuclei in an image of a nuclear component by determining the number of concave regions within the outline of the image. A second algorithm uses a measure of the amount of cytoplasmic material between a pair of nuclei to identify bi-nuclear cells. A third algorithm uses the statistics of the spatial distribution of objects to identify isolated pairs of nuclei which can be considered to be from the same cell.
摘要:
Methods, apparatus, and computer programs for investigating and characterising side effects of a treatment having an intended or on-target effect on cells are described. The method can include identifying a group of on-target cellular features of the plurality of cells which are affected by the treatment and are related to the on-target effect. A group of off-target cellular features can also be identified which are different to the on-target cellular features and which are also affected by the treatment and which are related to the side effect. A measure of the side effect based on the off-target cellular features can be obtained. The treatment can then be characterised based on the measure of the side effect. A further method involves capturing an image of the population of treated cells and deriving cellular features from the image. An on-target effect signature, which is characteristic of the on-target effect is created from cellular features relating to cellular properties involved in the intended effect. A side effect signature, which is characteristic of a side effect to the on-target effect, is created using cellular features relating to cellular properties not involved in the intended effect. On-target effect and/or side effect metrics are obtained from the signatures which can be used to characterise the treatment.
摘要:
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.
摘要:
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.
摘要:
Methods and apparatus, including computer program products, implementing and using techniques for analyzing images of cells and extraction of biologically significant features from the cell images, such as from granules representing intercellular organelles or other features in the images. In various embodiments, the extracted features can include the number of granules, the total surface area of the granules, the mean or maximum intensities of the granules, etc. These features can be determined on a cell-by cell basis, or for particular regions within a single cell, or for various groups of cells.
摘要:
According to the present invention, computer based techniques for using information technology in therapeutics or drug discovery. In an exemplary embodiment, computer based techniques for determining information about the properties of substances based upon information about structure of living or non-living cells exposed to substances are provided. Computer software according to the present invention enables researchers and/or scientists to identify promising candidates in the search for new and better medicines or treatments using, for example, a cellular informatics database.
摘要:
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.
摘要:
Methods for generating models for predicting biological activity of a stimulus test population of cells are provided. The models may be used to classify or predict the effect of stimuli on cells. In certain embodiments, the methods involve receiving data comprising values for dependent variables associated with stimuli as applied to cell populations; preparing a set of cell populations based on the data received; identifying a subset of the cell populations to be used in generating a model from data associated with the subset, wherein the model is provided to predict activity of a test population.
摘要:
Image analysis methods and apparatus are used for distinguishing live and dead cells. The methods may involve segmenting an image to identify the region(s) occupied by one or more cells and determining the presence of a particular live-dead indicator feature within the region(s). In certain embodiments, the indicator feature is a cytoskeletal component such as tubulin. In certain embodiments, the methods may involve determining the value of an indicator expression that is based on cellular components such as DNA and/or cellular protein. Prior to producing an image for analysis, cells may be treated with a marker that highlights the live-dead indicator in the image.