公开(公告)号：US08560243B2

公开(公告)日：2013-10-15

申请号：US11879161

申请日：2007-07-16

申请人： Matthew Marton ,  Roland Stoughton

发明人： Matthew Marton ,  Roland Stoughton

IPC分类号： G06F17/00 ,  G06F17/11

CPC分类号： C12Q1/6883 ,  C12Q1/025 ,  C12Q1/18 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/5005 ,  G01N33/5088 ,  G06F19/20 ,  G06F19/70

摘要： This invention provides methods for determining drug specificity, therapeutic index and effective doses for individual patients. According to the methods of the invention, graded levels of drug are applied to a biological sample or a patient. A plurality of cellular constituents are measured to determine the activity of the drug on a target pathway and at least one off-target pathway. A drug specificity is determined by comparing the target and off target activities of the drug. A therapeutic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the target pathway. A toxic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the off target pathway. Therapeutic index is the ratio of the toxic concentration over therapeutic concentration. Methods are also provided to determine an effective dose of a drug for a patient by measuring the activity of the drug on the particular patient.

摘要翻译： 本发明提供用于确定个体患者的药物特异性，治疗指数和有效剂量的方法。 根据本发明的方法，将分级药物施用于生物样品或患者。 测量多个细胞成分以确定药物在靶途径和至少一个脱靶途径上的活性。 通过比较药物的靶标和脱靶活性来确定药物特异性。 治疗浓度（或剂量）被定义为在目标途径中诱导一定反应的药物的浓度（或剂量）。 毒性浓度（或剂量）被定义为在脱靶途径中诱导某些反应的药物的浓度（或剂量）。 治疗指标是毒性浓度与治疗浓度的比值。 还提供了通过测量特定患者上的药物的活性来确定患者药物的有效剂量的方法。

公开(公告)号：US20070275407A1

公开(公告)日：2007-11-29

申请号：US11879161

申请日：2007-07-16

申请人： Matthew Marton ,  Roland Stoughton

发明人： Matthew Marton ,  Roland Stoughton

IPC分类号： C12Q1/68 ,  C12Q1/18 ,  G01N33/566

CPC分类号： C12Q1/6883 ,  C12Q1/025 ,  C12Q1/18 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/5005 ,  G01N33/5088 ,  G06F19/20 ,  G06F19/70

摘要： This invention provides methods for determining drug specificity, therapeutic index and effective doses for individual patients. According to the methods of the invention, graded levels of drug are applied to a biological sample or a patient. A plurality of cellular constituents are measured to determine the activity of the drug on a target pathway and at least one off-target pathway. A drug specificity is determined by comparing the target and off target activities of the drug. A therapeutic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the target pathway. A toxic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the off target pathway. Therapeutic index is the ratio of the toxic concentration over therapeutic concentration. Methods are also provided to determine an effective dose of a drug for a patient by measuring the activity of the drug on the particular patient.

公开(公告)号：US07254487B2

公开(公告)日：2007-08-07

申请号：US09823322

申请日：2001-04-02

申请人： Matthew Marton ,  Roland Stoughton

发明人： Matthew Marton ,  Roland Stoughton

IPC分类号： G01N33/48 ,  G01N31/00 ,  A01N37/18 ,  A01N43/04 ,  C12Q1/00 ,  C12Q1/68 ,  C12Q1/70 ,  C12P21/06

CPC分类号： C12Q1/6883 ,  C12Q1/025 ,  C12Q1/18 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/5005 ,  G01N33/5088 ,  G06F19/20 ,  G06F19/70

摘要： This invention provides methods for determining drug specificity, therapeutic index and effective doses for individual patients. According to the methods of the invention, graded levels of drug are applied to a biological sample or a patient. A plurality of cellular constituents are measured to determine the activity of the drug on a target pathway and at least one off-target pathway. A drug specificity is determined by comparing the target and off target activities of the drug. A therapeutic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the target pathway. A toxic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the off target pathway. Therapeutic index is the ratio of the toxic concentration over therapeutic concentration. Methods are also provided to determine an effective dose of a drug for a patient by measuring the activity of the drug on the particular patient.

摘要翻译： 本发明提供用于确定个体患者的药物特异性，治疗指数和有效剂量的方法。 根据本发明的方法，将分级药物施用于生物样品或患者。 测量多个细胞成分以确定药物在靶途径和至少一个脱靶途径上的活性。 通过比较药物的靶标和脱靶活性来确定药物特异性。 治疗浓度（或剂量）被定义为在目标途径中诱导一定反应的药物的浓度（或剂量）。 毒性浓度（或剂量）被定义为在脱靶途径中诱导某些反应的药物的浓度（或剂量）。 治疗指标是毒性浓度与治疗浓度的比值。 还提供了通过测量特定患者上的药物的活性来确定患者药物的有效剂量的方法。

公开(公告)号：US06222093B1

公开(公告)日：2001-04-24

申请号：US09222582

申请日：1998-12-28

申请人： Matthew Marton ,  Roland Stoughton

发明人： Matthew Marton ,  Roland Stoughton

IPC分类号： G01N3300

CPC分类号： C12Q1/6883 ,  C12Q1/025 ,  C12Q1/18 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/5005 ,  G01N33/5088 ,  G06F19/20 ,  G06F19/70

摘要： This invention provides methods for determining drug specificity, therapeutic index and effective doses for individual patients. According to the methods of the invention, graded levels of drug are applied to a biological sample or a patient. A plurality of cellular constituents are measured to determine the activity of the drug on a target pathway and at least one off-target pathway. A drug specificity is determined by comparing the target and off target activities of the drug. A therapeutic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the target pathway. A toxic concentration (or dose) is defined as a concentration (or dose) of the drug that induces certain response in the off target pathway. Therapeutic index is the ratio of the toxic concentration over therapeutic concentration. Methods are also provided to determine an effective dose of a drug for a patient by measuring the activity of the drug on the particular patient.

摘要翻译： 本发明提供用于确定个体患者的药物特异性，治疗指数和有效剂量的方法。 根据本发明的方法，将分级药物施用于生物样品或患者。 测量多个细胞成分以确定药物在靶途径和至少一个脱靶途径上的活性。 通过比较药物的靶标和脱靶活性来确定药物特异性。 治疗浓度（或剂量）被定义为在目标途径中诱导一定反应的药物的浓度（或剂量）。 毒性浓度（或剂量）被定义为在脱靶途径中诱导某些反应的药物的浓度（或剂量）。 治疗指标是毒性浓度与治疗浓度的比值。 还提供了通过测量特定患者上的药物的活性来确定患者药物的有效剂量的方法。

公开(公告)号：US20110171638A1

公开(公告)日：2011-07-14

申请号：US12725240

申请日：2010-03-16

申请人： Roland Stoughton ,  Ravi Kapur ,  Barb Ariel Cohen

发明人： Roland Stoughton ,  Ravi Kapur ,  Barb Ariel Cohen

IPC分类号： C12Q1/68

CPC分类号： G01N1/30 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/158 ,  C12Q2600/16 ,  G16B20/00

摘要： The present invention provides systems, apparatuses, and methods to detect the presence of fetal cells when mixed with a population of maternal cells in a sample and to test fetal abnormalities, i.e. aneuploidy. In addition, the present invention provides methods to determine when there are insufficient fetal cells for a determination and report a non-informative case. The present invention involves quantifying regions of genomic DNA from a mixed sample. More particularly the invention involves quantifying DNA polymorphisms from the mixed sample.

摘要翻译： 本发明提供了当与样品中的母体细胞群混合时检测胎儿细胞的存在并测试胎儿异常（即非整倍体）的系统，装置和方法。 此外，本发明提供了确定何时胎儿细胞不足以确定并报告非信息性病例的方法。 本发明涉及量化来自混合样品的基因组DNA的区域。 更具体地，本发明涉及从混合样品中定量DNA多态性。

公开(公告)号：US07565251B2

公开(公告)日：2009-07-21

申请号：US11303121

申请日：2005-12-12

申请人： Roland Stoughton ,  Hongyue Dai

发明人： Roland Stoughton ,  Hongyue Dai

IPC分类号： G01N33/50

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。

公开(公告)号：US20070026391A1

公开(公告)日：2007-02-01

申请号：US11398998

申请日：2006-04-06

申请人： Roland Stoughton ,  Michael Meyer ,  Daniel Shoemaker

发明人： Roland Stoughton ,  Michael Meyer ,  Daniel Shoemaker

IPC分类号： C12Q1/70 ,  C12Q1/68

CPC分类号： G01N33/569 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y15/00 ,  G01N33/54306 ,  G01N33/582 ,  G01N33/588 ,  Y02A50/52 ,  Y02A50/53 ,  Y02A50/55

摘要： The present invention provides methods for detecting a target pathogenic agent, e.g., a virus, a bacterium, and/or a toxic substance, using colocalization detection. The invention also provides methods for parallel detection of different target pathogenic agents in a sample using multiplexed labeling and colocalization detection. The invention also provides kits comprising sets of probes for detecting pathogenic agents. The invention further provides computer systems and computer program products for carrying out the method of determining degrees of colocalization.

摘要翻译： 本发明提供了使用共定位检测来检测靶病原体，例如病毒，细菌和/或有毒物质的方法。 本发明还提供了使用多重标记和共定位检测在样品中并行检测不同靶病原体的方法。 本发明还提供了包括用于检测病原体的探针组的试剂盒。 本发明还提供了用于执行确定共定位度的方法的计算机系统和计算机程序产品。

公开(公告)号：US20060190191A1

公开(公告)日：2006-08-24

申请号：US11303121

申请日：2005-12-12

申请人： Roland Stoughton ,  Hongyue Dai

发明人： Roland Stoughton ,  Hongyue Dai

IPC分类号： 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.

公开(公告)号：US06859735B1

公开(公告)日：2005-02-22

申请号：US09374565

申请日：1999-08-13

申请人： Roland Stoughton ,  Stephen H. Friend

发明人： Roland Stoughton ,  Stephen H. Friend

IPC分类号： G01N33/53 ,  C12N15/09 ,  C12Q1/02 ,  C12Q1/04 ,  C12Q1/68 ,  G06F19/12 ,  G01N33/48 ,  C12P21/06 ,  G06G7/48

CPC分类号： G06F19/12 ,  C12Q1/025 ,  G01N33/5041

摘要： The present invention provides methods and computer systems for identifying and representing the biological pathways of drug action on a cell The present invention also provides methods and computer systems for assessing the significance of the identified representation and for verifying that the identified pathways are actual pathway of drug action. The present invention also provides methods and computer systems for drug development based on the methods for identifying biological pathways of drug action, and methods and computer systems for representing the biological pathways involved in the effect of an environmental change upon a cell.

摘要翻译： 本发明提供用于鉴定和表示药物作用于细胞的生物学途径的方法和计算机系统本发明还提供了用于评估所鉴定的表现的重要性并用于验证所鉴定的途径是药物的实际途径的方法和计算机系统 行动。 本发明还提供了用于鉴定药物作用的生物学途径的方法的用于药物开发的方法和计算机系统，以及用于表示涉及环境变化对细胞的影响的生物学途径的方法和计算机系统。

公开(公告)号：US06132969A

公开(公告)日：2000-10-17

申请号：US99722

申请日：1998-06-19

申请人： Roland Stoughton ,  Richard M. Karp

发明人： Roland Stoughton ,  Richard M. Karp

IPC分类号： G01N33/50 ,  C12N15/09 ,  C12Q1/06 ,  C12Q1/68 ,  C12R1/865 ,  G01N33/15 ,  G06F19/12 ,  C12Q1/00 ,  G01N33/53 ,  G06F17/00

CPC分类号： G06F19/12

摘要： The present invention provides methods and systems for testing and confirming how well a network model represents a biological pathway in a biological system. The network model comprises a network of logical operators relating input cellular constituents (e.g., mRNA or protein abundances) to output classes of cellular constituents, which are affected by the pathway in the biological system. The methods of this invention provide, first, for choosing complete and efficient experiments for testing the network model which compare relative changes in the biological system in response to perturbations of the network. The methods also provide for determining an overall goodness of fit of the network model to biological system by: predicting from the network model how output classes behave in response to the chosen experiments, finding measures of relative change of cellular constituents actually observed in the chosen experiments, finding goodnesses of fit of each observed cellular constituent to an output class with which the cellular constituent has the strongest correlation, and determining an overall goodness of fit of the network model from the individual goodnesses of fit of each observed cellular constituent. Additionally, these methods provide for testing the significance of the overall goodness of fit according to a nonparametric statistical test using an empirically determined distribution of possible goodnesses of fit. This invention also provides for computer systems for carrying out the computational steps of these methods.

摘要翻译： 本发明提供用于测试和确认网络模型在生物系统中代表生物学途径的方式和系统。 网络模型包括将输入细胞成分（例如，mRNA或蛋白质丰度）与输出生物系统中途径影响的细胞成分类型相关联的逻辑运算器网络。 本发明的方法首先提供用于选择用于测试网络模型的完整和有效的实验，该网络模型响应于网络的扰动来比较生物系统中的相对变化。 该方法还提供了通过以下方式来确定网络模型对生物系统的整体拟合度：从网络模型预测输出类型如何响应于所选择的实验而行为，找到在所选实验中实际观察到的细胞成分的相对变化的度量 将每个观察到的细胞成分适合于细胞成分具有最强相关性的输出类别，并根据每个观察到的细胞成分的拟合优度确定网络模型的整体拟合度。 此外，这些方法提供了使用经验确定的可能的适合度的分布来根据非参数统计检验测试整体拟合度的重要性。 本发明还提供了用于执行这些方法的计算步骤的计算机系统。