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1. 发明申请

US20090034822A1 Methods and Apparatus for Characterising Cells and Treatments 审中-公开
标题翻译：用于表征细胞和治疗的方法和装置
公开(公告)号：US20090034822A1
公开(公告)日：2009-02-05
申请号：US12130850
申请日：2008-05-30
申请人： Daniel A. Coleman , Ge Cong , Aibing Rao , Eugeni A. Vaisberg
发明人： Daniel A. Coleman , Ge Cong , Aibing Rao , Eugeni A. Vaisberg
IPC分类号： G06K9/00
CPC分类号： G06K9/0014 , G06T7/0012 , G06T2207/30024
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.
摘要翻译：公开了用于表征细胞的方法，数据处理装置和计算机程序产品以及对细胞施用的治疗的影响。描述了特定的识别双核细胞的方法，其包括捕获多个标记细胞的图像和处理图像以获得多个细胞的特征。分析特征以确定特征是否表示双核细胞。第一特征指示双核细胞的那些细胞被鉴定为双核的。具体描述三种算法。可以使用第一算法来确定图像轮廓内的凹区域的数量来确定核分量的图像中的核的数量。第二种算法使用一对核之间的细胞质材料的量的量度来识别双核细胞。第三种算法使用对象的空间分布的统计来识别可以被认为来自相同小区的孤立的核对。

2. 发明授权

US07151847B2 Image analysis of the golgi complex 失效
公开(公告)号：US07151847B2
公开(公告)日：2006-12-19
申请号：US09792012
申请日：2001-02-20
申请人： Eugeni A. Vaisberg , Ge Cong , Hsien-Hsun Wu
发明人： Eugeni A. Vaisberg , Ge Cong , Hsien-Hsun Wu
IPC分类号： G06K9/00
CPC分类号： G06K9/0014 , G01N15/1475 , G01N2015/1006 , G01N2015/1472 , G01N2015/149 , G06K9/00127
摘要： Methods, code and apparatus analyze cell images to automatically identify and characterize the Golgi complex in individual cells. This is accomplished by first locating the cells in the image and defining boundaries of those cells that subsume some or all of the Golgi complex of those cells. The Golgi complex in the images typically have intensity values corresponding to the concentration of a Golgi component in the cell (e.g. a polysaccharide associated with the Golgi complex). The method/system then analyzes the Golgi components of the image (typically on a pixel-by-pixel basis) to mathematically characterize the Golgi complex of individual cells. This mathematical characterization represents phenotypic information about the cells' Golgi complex and can be used to classify cells. From this information, mechanism of action and other important biological information can be deduced.

3. 发明授权

US06956961B2 Extracting shape information contained in cell images 有权
公开(公告)号：US06956961B2
公开(公告)日：2005-10-18
申请号：US09792013
申请日：2001-02-20
申请人： Ge Cong , Eugeni A. Vaisberg
发明人： Ge Cong , Eugeni A. Vaisberg
IPC分类号： G01N15/00 , G01N15/14 , G06K9/00 , G06T1/40 , G06T5/00 , G06T5/30 , G06T7/00
CPC分类号： G06K9/0014 , G01N15/14 , G01N2015/0065 , G01N2015/1497 , G06T7/0012 , G06T7/12 , G06T7/155 , G06T7/62 , G06T7/66 , G06T2207/10056 , G06T2207/20044 , G06T2207/20152 , G06T2207/30024
摘要： Methods and apparatus are provided for the analysis of images of cells and extraction biologically-significant shape-related features from the cell images. The extracted features may be correlated with particular conditions induced by biologically-active agents with which cells have been treated, thereby enabling the automated analysis of cells based on cell shape parameters. In particular, the invention provides methods for segmentation of cells in an image using a combination of a reference component image data and cell shape-indicative marker image data in a watershed technique. Further, the invention provides a skeletonization and skeleton analysis technique for extracting biologically-relevant features from cell shapes.

4. 发明授权

US07269278B2 Extracting shape information contained in cell images 失效
标题翻译：提取细胞图像中包含的形状信息
公开(公告)号：US07269278B2
公开(公告)日：2007-09-11
申请号：US11165914
申请日：2005-06-24
申请人： Ge Cong , Eugeni A. Vaisberg
发明人： Ge Cong , Eugeni A. Vaisberg
IPC分类号： G06K9/00 , G06K9/34
CPC分类号： G06K9/0014 , G01N15/14 , G01N2015/0065 , G01N2015/1497 , G06T7/0012 , G06T7/12 , G06T7/155 , G06T7/62 , G06T7/66 , G06T2207/10056 , G06T2207/20044 , G06T2207/20152 , G06T2207/30024
摘要： Methods and apparatus are provided for the analysis of images of cells and extraction biologically-significant shape-related features from the cell images. The extracted features may be correlated with particular conditions induced by biologically-active agents with which cells have been treated, thereby enabling the automated analysis of cells based on cell shape parameters. In particular, the invention provides methods for segmentation of cells in an image using a combination of a reference component image data and cell shape-indicative marker image data in a watershed technique. Further, the invention provides a skeletonization and skeleton analysis technique for extracting biologically-relevant features from cell shapes.
摘要翻译：提供了方法和装置，用于细胞图像的分析和从细胞图像提取生物学显着的形状相关特征。提取的特征可以与由细胞已被处理的生物活性剂诱导的特定条件相关，从而使得能够基于细胞形状参数自动分析细胞。具体地，本发明提供了使用分水岭技术中的参考分量图像数据和细胞形状指示标记图像数据的组合来分割图像中的细胞的方法。此外，本发明提供了用于从细胞形状提取生物相关特征的骨架化和骨架分析技术。

5. 发明授权

US07218764B2 Ploidy classification method 失效
标题翻译：倍性分类法
公开(公告)号：US07218764B2
公开(公告)日：2007-05-15
申请号：US11097451
申请日：2005-04-01
申请人： Eugeni A. Vaisberg , Daniel A. Coleman
发明人： Eugeni A. Vaisberg , Daniel A. Coleman
IPC分类号： G06K9/00
CPC分类号： G01N33/5005
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.
摘要翻译：图像分析方法和装置用于确定细胞的倍性。所述方法可以包括分割图像以识别由单元或核占据的一个或多个离散区域，确定区域内特定倍性指示符特征的存在，以及将指示符特征的值提供给将细胞分类的模型在指标特征的基础上进行倍性。在一些实施方案中，指示剂特征是细胞中的DNA水平。在某些实施方案中，所述方法还包括用突出所述倍性指示物特征的标记物处理一个或多个细胞。在某些实施方案中，在产生一个或多个细胞的一个或多个图像之前处理细胞。在某些实施方案中，倍性指示物特征包括DNA，并且标记物与DNA共定位并提供在图像中捕获的信号。在某些实施例中，信号包括荧光发射。

6. 发明授权

US06876760B1 Classifying cells based on information contained in cell images 有权
标题翻译：根据细胞图像中包含的信息对细胞进行分类
公开(公告)号：US06876760B1
公开(公告)日：2005-04-05
申请号：US09729754
申请日：2000-12-04
申请人： Eugeni A. Vaisberg , Daniel A. Coleman
发明人： Eugeni A. Vaisberg , Daniel A. Coleman
IPC分类号： G06K9/00 , G06T5/00 , G06T7/60
CPC分类号： G06K9/0014 , G06T7/11 , G06T7/60 , G06T2207/10056 , G06T2207/10064 , G06T2207/30024
摘要： 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: G1, S, G2, telophase, and an early stage mitotic phase comprised of prophase, metaphase, and anaphase.
摘要翻译：图像分析方法基于从图像提取的特征，分析细胞的图像并将细胞置于特定的细胞周期阶段。该方法还可以基于特异性特征（例如来自结合DNA的荧光分子的荧光强度）来量化细胞中DNA的总量。此外，所述方法可以基于所选择的参数（例如在细胞图像中观察到的强度变化）和/或含有DNA的区域的大小来表征细胞作为有丝分裂或间期。在一个实例中，图像分析方法可以将细胞分为以下五个阶段之一：G1，S，G2，端粒酶，以及由前期，中期和后期组成的早期有丝分裂期。

7. 发明授权

US06738716B1 Database system for predictive cellular bioinformatics 有权
公开(公告)号：US06738716B1
公开(公告)日：2004-05-18
申请号：US09718766
申请日：2000-11-21
申请人： James H. Sabry , Cynthia L. Adams , Eugeni A. Vaisberg , Anne M. Crompton
发明人： James H. Sabry , Cynthia L. Adams , Eugeni A. Vaisberg , Anne M. Crompton
IPC分类号： G01N3348
CPC分类号： G06K9/00127 , C12M41/36 , C12M41/46 , G06F19/24 , G06T7/0012 , G06T2207/30024 , Y10S707/99933 , Y10S707/99934 , Y10S707/99936
摘要： A system for acquiring knowledge from cellular information. The system has a database comprising a database management module (“DBMS”). The system also has a variety of modules, including a population module coupled to the DBMS for categorizing and storing a plurality of features (e.g., cell size, distance between cells, cell population, cell type) from an image acquisition device into the database. The system has a translation module coupled to the DBMS for defining a descriptor from a set of selected features from the plurality of features. In a specific embodiment, the descriptor is for a known or unknown compound, e.g., drug. A prediction module is coupled to the DBMS for selecting one of a plurality of a descriptors from known and unknown compounds from the database based upon a selected descriptor from a selected compound. The selected compound may be one that is useful for treatment of human beings or the like.

8. 发明授权

US06615141B1 Database system for predictive cellular bioinformatics 失效
标题翻译：用于预测细胞生物信息学的数据库系统
公开(公告)号：US06615141B1
公开(公告)日：2003-09-02
申请号：US09718704
申请日：2000-11-21
申请人： James H. Sabry , Cynthia L. Adams , Eugeni A. Vaisberg , Anne M. Crompton
发明人： James H. Sabry , Cynthia L. Adams , Eugeni A. Vaisberg , Anne M. Crompton
IPC分类号： G01N3348
CPC分类号： G06K9/00127 , C12M41/36 , C12M41/46 , G06F19/24 , G06T7/0012 , G06T2207/30024 , Y10S707/99933 , Y10S707/99934 , Y10S707/99936
摘要： A system for acquiring knowledge from cellular information. The system has a database comprising a database management module (“DBMS”). The system also has a variety of modules, including a population module coupled to the DBMS for categorizing and storing a plurality of features (e.g., cell size, distance between cells, cell population, cell type) from an image acquisition device into the database. The system has a translation module coupled to the DBMS for defining a descriptor from a set of selected features from the plurality of features. In a specific embodiment, the descriptor is for a known or unknown compound, e.g., drug. A prediction module is coupled to the DBMS for selecting one of a plurality of a descriptors from known and unknown compounds from the database based upon a selected descriptor from a selected compound. The selected compound may be one that is useful for treatment of human beings or the like.
摘要翻译：用于从蜂窝信息获取知识的系统。该系统具有包括数据库管理模块（“DBMS”）的数据库。该系统还具有各种模块，包括耦合到DBMS的群模块，用于从图像采集设备将多个特征（例如，小区大小，小区之间的距离，小区群，小区类型）分类和存储到数据库中。该系统具有耦合到DBMS的翻译模块，用于从多个特征的一组选定特征中定义描述符。在具体实施方案中，描述符是用于已知或未知的化合物，例如药物。预测模块耦合到DBMS，用于基于来自所选化合物的所选择的描述符从数据库中选择来自已知和未知化合物的多个描述符之一。所选择的化合物可以是可用于治疗人类等的化合物。

9. 发明授权

US07657076B2 Characterizing biological stimuli by response curves 失效
标题翻译：通过响应曲线表征生物刺激
公开(公告)号：US07657076B2
公开(公告)日：2010-02-02
申请号：US11186143
申请日：2005-07-20
申请人： Eugeni A. Vaisberg , Donald R. Oestreicher , Cynthia L. Adams
发明人： Eugeni A. Vaisberg , Donald R. Oestreicher , Cynthia L. Adams
IPC分类号： G06K9/00 , G06K9/20 , G06K9/36 , G06F19/00
CPC分类号： G06K9/6253 , G06F19/70 , G06K9/00127
摘要： A method for generating stimulus response curves (e.g., dose response curves) shows how the phenotype of one or more cells change in response to varying levels of the stimulus. Each “point” on the curve represents quantitative phenotype for cell(s) at a particular level of stimulus (e.g., dose of a therapeutic). The quantitative phenotypes are multivariate phenotypic representations of the cell(s). They include various features of the cell(s) obtained by image analysis. Such features often include basic parameters obtained from images (e.g., cell shape, nucleus area, Golgi texture) and/or biological characterizations derived from the basic parameters (e.g., cell cycle state, mitotic index, etc.). The stimulus response curves may be compared to allow classification of stimuli and identify subtle differences in related stimuli. To facilitate the comparison, it may be desirable to present the response curves in a principal component space.
摘要翻译：用于产生刺激响应曲线（例如，剂量反应曲线）的方法示出了一种或多种细胞的表型如何响应于刺激的不同水平而改变。曲线上的每个“点”表示在特定刺激水平（例如治疗剂的剂量）下的细胞的定量表型。定量表型是细胞的多变量表型表达。它们包括通过图像分析获得的细胞的各种特征。这些特征通常包括从基本参数（例如细胞周期状态，有丝分裂指数等）导出的图像（例如，细胞形状，细胞核区域，高尔基体织构）和/或生物学表征获得的基本参数。可以比较刺激反应曲线以允许刺激分类并识别相关刺激的微妙差异。为了便于比较，可能期望在主要分量空间中呈现响应曲线。

10. 发明授权

US07246012B2 Characterizing biological stimuli by response curves 失效
标题翻译：通过响应曲线表征生物刺激
公开(公告)号：US07246012B2
公开(公告)日：2007-07-17
申请号：US10892450
申请日：2004-07-16
申请人： Vadim Kutsyy , Daniel A. Coleman , Eugeni A. Vaisberg
发明人： Vadim Kutsyy , Daniel A. Coleman , Eugeni A. Vaisberg
IPC分类号： G06K9/00 , G01N33/48
CPC分类号： G06K9/6274 , G06K9/00147 , G06K9/00536
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.
摘要翻译：用于计算刺激响应曲线（例如，剂量响应曲线）之间的距离的方法允许对刺激进行分类。响应曲线显示了一种或多种细胞的表型如何响应刺激的不同水平而改变。曲线上的每个“点”表示特定刺激水平（例如，治疗剂的剂量）的细胞的定量表型或特征。签名是细胞的多变量表型表达。它们包括通过图像分析获得的细胞的各种特征。为了促进刺激的比较，计算响应曲线上的点之间的距离。首先，响应曲线可以在表示来自负控制的公共点（例如，不施加刺激的点）的单独距离r的坐标上对准。可以使用r上的积分来计算两个响应曲线之间的距离。响应曲线之间的距离用于对刺激进行分类。

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