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    Methods of diagnosing disease states using gene expression profiles
    35.
    发明授权
    Methods of diagnosing disease states using gene expression profiles 失效
    使用基因表达谱诊断疾病状态的方法

    公开(公告)号：US06973388B2

    公开(公告)日：2005-12-06

    申请号：US09783474

    申请日：2001-02-14

    申请人： Stephen H. Friend ,  Roland Stoughton

    发明人： Stephen H. Friend ,  Roland Stoughton

    IPC分类号： G01D1/16 ,  A01N43/04 ,  A01N61/00 ,  C07H21/04 ,  C12M20060101 ,  C12M1/34 ,  C12M3/00 ,  C12N15/09 ,  C12P21/06 ,  C12Q1/02 ,  C12Q1/68 ,  G01N33/48 ,  G01N33/53 ,  G01N37/00 ,  G06G7/48

    CPC分类号： C12Q1/6886 ,  C12Q2600/156 ,  C12Q2600/158

    摘要： The present invention provides methods for monitoring disease states in a subject, as well as methods for monitoring the levels of effect of therapies upon a subject having one or more disease states. The methods involve: (i) measuring abundances of cellular constituents in a cell from a subject to obtain a diagnostic profile, (ii) measuring abundances of cellular constituents in a cell of one or more analogous subjects to obtain perturbation response profiles which correlate to a particular disease or therapy, and (iii) determining the interpolated perturbation response profile or profiles which best fit the diagnostic profile. In other aspects, the invention also provides a computer system capable of performing the methods of the invention, databases comprising perturbation response profiles for one or more diseases and/or therapies, and kits for determining levels of disease states and/or therapeutic effects according to the methods of the invention.

    摘要翻译： 本发明提供了用于监测受试者的疾病状态的方法，以及用于监测治疗对具有一种或多种疾病状态的受试者的疗效水平的方法。 所述方法包括：（i）测量来自受试者的细胞中的细胞成分的丰度以获得诊断特征，（ii）测量一个或多个类似受试者的细胞中细胞成分的丰度，以获得与a相关的扰动反应曲线 特定疾病或治疗，以及（iii）确定最适合诊断特征的内插扰动响应曲线或轮廓。 在其他方面，本发明还提供一种能够执行本发明的方法的计算机系统，包括用于一种或多种疾病和/或治疗的扰动反应概况的数据库，以及用于确定根据本发明的疾病状态和/或治疗效果水平的试剂盒 本发明的方法。

    Statistical combining of cell expression profiles
    36.
    发明申请
    Statistical combining of cell expression profiles 失效
    细胞表达谱的统计学结合

    公开(公告)号：US20050164273A1

    公开(公告)日：2005-07-28

    申请号：US11042654

    申请日：2005-01-24

    申请人： Roland Stoughton ,  Hongyue Dai

    发明人： Roland Stoughton ,  Hongyue Dai

    IPC分类号： G01N33/53 ,  C12N15/09 ,  C12Q1/68 ,  G01N33/48 ,  G01N33/566 ,  G01N33/58 ,  G01N37/00 ,  G06F17/18 ,  G06F19/20 ,  G01N33/50 ,  G06F19/00

    CPC分类号： G06F19/20 ,  C12Q1/6837 ,  Y10T436/10

    摘要： A method for fluorophore bias removal in microarray experiments in which the fluorophores used in microarray experiment pairs are reversed. Further, a method for calculating the individual errors associated with each measurement made in nominally repeated microarray experiments. This error measurement is optionally coupled with rank based methods in order to determine a probability that a cellular constituent is up or down regulated in response to a perturbation. Finally, a method for determining the confidence in the weighted average of the expression level of a cellular constituent in nominally repeated microarray experiments.

    摘要翻译： 用于微阵列实验对中的荧光团的微阵列实验中的荧光团偏置去除方法是相反的。 此外，一种用于计算与名义上重复的微阵列实验中进行的每个测量相关联的各个错误的方法。 该误差测量可选地与基于秩的方法耦合，以便确定响应于扰动的细胞成分向上或向下调节的概率。 最后，在名义上重复的微阵列实验中确定细胞成分的表达水平的加权平均的置信度的方法。

    Methods for using-co-regulated genesets to enhance detection and classification of gene expression patterns
    37.
    发明授权
    Methods for using-co-regulated genesets to enhance detection and classification of gene expression patterns 失效
    使用共同调控的基因组的方法来增强基因表达模式的检测和分类

    公开(公告)号：US06468476B1

    公开(公告)日：2002-10-22

    申请号：US09428427

    申请日：1999-10-27

    申请人： Stephen H. Friend ,  Roland Stoughton ,  Yudong He

    发明人： Stephen H. Friend ,  Roland Stoughton ,  Yudong He

    IPC分类号： G01N1500

    CPC分类号： G06F19/24 ,  C12Q1/6809 ,  C12Q1/6834 ,  G01N33/6803 ,  G06F19/20

    摘要： The present invention provides methods for enhanced detection of biological response patterns. In one embodiment of the invention, genes are grouped into basis genesets according to the co-regulation of their expression. Expression of individual genes within a geneset is indicated with a single gene expression value for the geneset by a projection process. The expression values of genesets, rather than the expression of individual genes, are then used as the basis for comparison and detection of biological response with greatly enhanced sensitivity. In another embodiment of the invention, biological responses are grouped according to the similarity of their biological profile. The methods of the invention have many useful applications, particularly in the fields of drug development and discovery. For example, the methods of the invention may be used to compare biological responses with greatly enhanced sensitivity. The biological responses that may be compared according to these methods include responses to single perturbations, such as a biological response to a mutation or temperature change, as well as graded perturbations such as titration with a particular drug. The methods are also useful to identify cellular constituents, particularly genes, associated with a particular type of biological response. Further, the methods may also be used to identify perturbations, such as novel drugs or mutations, which effect one or more particular genesets. The methods may still further be used to remove experimental artifacts in biological response data.

    摘要翻译： 本发明提供了用于增强生物反应模式检测的方法。 在本发明的一个实施方案中，根据其表达的共调节将基因分组成基因基因组。 个体基因在基因组中的表达用投影过程的基因表达值表示。 然后将基因的表达值，而不是单个基因的表达值作为比较和检测生物反应的基础，大大提高敏感性。 在本发明的另一个实施方案中，生物反应根据其生物学特征的相似性进行分组。本发明的方法具有许多有用的应用，特别是在药物开发和发现领域。 例如，本发明的方法可用于比较具有极大增强的灵敏度的生物反应。 可以根据这些方法比较的生物反应包括对单一扰动的反应，例如对突变或温度变化的生物反应，以及分级扰动，例如用特定药物滴定。 所述方法还可用于鉴定与特定类型的生物反应相关的细胞成分，特别是基因。 此外，所述方法还可用于鉴定影响一个或多个特定基因组的扰动，例如新型药物或突变。 这些方法还可以进一步用于去除生物反应数据中的实验伪影。

    Methods of determining protein activity levels using gene expression profiles
    38.
    发明授权
    Methods of determining protein activity levels using gene expression profiles 失效
    使用基因表达谱确定蛋白质活性水平的方法

    公开(公告)号：US06324479B1

    公开(公告)日：2001-11-27

    申请号：US09303082

    申请日：1999-04-30

    申请人： Stephen H. Friend ,  Roland Stoughton

    发明人： Stephen H. Friend ,  Roland Stoughton

    IPC分类号： G01N3348

    CPC分类号： C07K14/4702 ,  A61K38/00

    摘要： The present invention provides methods for determining the level of protein activity in a cell by: (i) measuring abundances of cellular constituents in a cell in which the activity of a specific protein is to be determined so that a diagnostic profile is thus obtained; (ii) measuring abundances of cellular constituents that occur in a cell in response to perturbations in the activity of said protein to obtain response profiles and interpolating said response profiles to generate response curves; and (iii) determining a protein activity level at which the response profile extracted from the response curves best fits the measured diagnostic profile, according to some objective measure. In alternative embodiments, the present invention also provides methods for identifying individuals having genetic mutations or polymorphisms that disrupt protein activity, and methods for identifying drug activity in vivo by determining the activity levels of proteins which interact with said drugs.

    摘要翻译： 本发明提供了通过以下步骤确定细胞中蛋白质活性水平的方法：（i）测量要确定特定蛋白质的活性的细胞中细胞成分的丰度，从而获得诊断特征; （ii）测量在细胞中发生的细胞成分的丰度以响应所述蛋白质的活动中的扰动以获得反应谱并内插所述响应谱以产生响应曲线; 和（iii）根据一些客观的测定，确定从响应曲线提取的反应曲线最适合测量的诊断谱的蛋白质活性水平。 在替代实施方案中，本发明还提供了用于鉴定具有破坏蛋白质活性的遗传突变或多态性的个体的方法，以及通过测定与所述药物相互作用的蛋白质的活性水平来鉴定体内药物活性的方法。

    Computer system and method for determining a number of primary targets of a drug
    39.
    发明授权
    Computer system and method for determining a number of primary targets of a drug 失效
    用于确定药物的主要靶标数目的计算机系统和方法

    公开(公告)号：US06300078B1

    公开(公告)日：2001-10-09

    申请号：US09693642

    申请日：2000-10-20

    申请人： Stephen H. Friend ,  Roland Stoughton

    发明人： Stephen H. Friend ,  Roland Stoughton

    IPC分类号： C12Q168

    CPC分类号： G01N33/50 ,  C12Q1/6809 ,  G01N33/5041 ,  G06F19/18 ,  G06F19/20

    摘要： This invention relates to methods and systems for characterizing the actions of drugs in cells. In particular, the invention provides methods for identifying multiple primary targets through which a drug, drug candidate, or other compound of interest acts on a cell. Thus, the invention also relates to methods for drug development based on the disclosed methods for identifying multiple primary targets of a drug. The methods of the invention involve: (i) measuring responses of cellular constituents to graded exposures of the cell to a drug of interest; (ii) identifying an “inflection concentration” of the drug for each cellular constituent measured; and (iii) identifying “expression sets” of cellular constituents from the distribution of the inflection drug concentrations. Each expression set corresponds to a particular primary target of the drug. The invention also provides computer systems which identify multiple targets of a drug by executing the disclosed methods.

    摘要翻译： 本发明涉及用于表征细胞中药物作用的方法和系统。 特别地，本发明提供了用于鉴定药物，候选药物或其它感兴趣的化合物通过其作用于细胞的多个主要靶标的方法。 因此，本发明还涉及基于所公开的用于鉴定药物的多个主要靶标的方法的用于药物开发的方法。 本发明的方法涉及：（i）测量细胞成分对细胞分级暴露于感兴趣的药物的反应; （ii）确定所测量的每种细胞成分的药物的“转折浓度”; 和（iii）从转折药物浓度的分布中鉴定细胞成分的“表达组”。 每个表达集对应于药物的特定主要靶标。 本发明还提供了通过执行所公开的方法来鉴定药物的多个靶标的计算机系统。

    Methods of monitoring disease states and therapies using gene expression profiles
    40.
    发明授权
    Methods of monitoring disease states and therapies using gene expression profiles 失效

    公开(公告)号：US06218122B1

    公开(公告)日：2001-04-17

    申请号：US09334328

    申请日：1999-06-16

    申请人： Stephen H. Friend ,  Roland Stoughton

    发明人： Stephen H. Friend ,  Roland Stoughton

    IPC分类号： C12Q168

    CPC分类号： C12Q1/6886 ,  C12Q2600/156 ,  C12Q2600/158

    摘要： The present invention provides methods for monitoring disease states in a subject, as well as methods for monitoring the levels of effect of therapies upon a subject having one or more disease states. The methods involve: (i) measuring abundances of cellular constituents in a cell from a subject so that a diagnostic profile is obtained, (ii) measuring abundances of cellular constituents in a cell of one or more analogous subjects so that perturbation response profiles are obtained which correlate to a particular disease or therapy, and (iii) determining the interpolated perturbation response profile or profiles which best fit the diagnostic profile according to some objective measure. In other aspects, the invention also provides a computer system capable of performing the methods of the invention, data bases comprising perturbation response profiles for one or more diseases and/or therapies, and kits for determining levels of disease states and/or therapeutic effects according to the methods of the invention.