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    Complexity management and analysis of genomic DNA
    33.
    发明授权
    Complexity management and analysis of genomic DNA 有权
    基因组DNA的复杂性管理与分析

    公开(公告)号：US07267966B2

    公开(公告)日：2007-09-11

    申请号：US09904039

    申请日：2001-07-12

    Applicant: Shoulian Dong ,  Robert J. Lipshutz ,  David Lockhart

    Inventor： Shoulian Dong ,  Robert J. Lipshutz ,  David Lockhart

    IPC: C12P19/34 ,  C12Q1/68

    CPC classification number: C12Q1/6837 ,  C12Q1/6855 ,  C12Q1/6858 ,  C12Q2600/156 ,  Y10S977/924 ,  C12Q2531/113 ,  C12Q2525/191 ,  C12Q2521/313 ,  C12Q2563/143

    Abstract: The present invention provides for novel methods of sample preparation and analysis involving reproducibly reducing the complexity of a nucleic sample. The invention further provides for analysis of the above sample by hybridization to an array which may be specifically designed to interrogate the desired fragments for particular characteristics, such as, for example, the presence or absence of a polymorphism. The invention further provides for novel methods of using a computer system to model enzymatic reactions in order to determine experimental conditions before conducting actual experiments.

    Abstract translation: 本发明提供了重复地降低核酸样品的复杂性的样品制备和分析的新方法。 本发明进一步提供了通过与阵列的杂交来分析上述样品，所述阵列可被特别设计成询问特定特征的期望片段，例如多态性的存在或不存在。 本发明进一步提供了使用计算机系统来模拟酶反应以便在进行实际实验之前确定实验条件的新方法。

    METHODS OF GENE EXPRESSION MONITORING
    34.
    发明申请
    METHODS OF GENE EXPRESSION MONITORING 审中-公开
    基因表达监测方法

    公开(公告)号：US20060292614A1

    公开(公告)日：2006-12-28

    申请号：US11467971

    申请日：2006-08-29

    Applicant: Yanxiang Cao ,  Lubert Stryer ,  David Lockhart ,  Catherine Dulac ,  Ian Tietjen ,  Jason Rihel

    Inventor： Yanxiang Cao ,  Lubert Stryer ,  David Lockhart ,  Catherine Dulac ,  Ian Tietjen ,  Jason Rihel

    IPC: C12Q1/68

    CPC classification number: C12Q1/6809 ,  C12Q2565/501

    Abstract: The invention provides methods of monitoring expression of a plurality of genes in a cell or small population of cells. Preferred methods entail contacting an array of probes with a population of nucleic acids derived from a population of fewer than 1000 cells then determining the relative hybridization of the probes to the population of nucleic acid as a measure of the relative representation of genes from the cells. The invention further provides methods of classifying cells. These preferred methods entail determining an expression profile of each of a plurality of cells then classifying the cells in clusters determined by similarity of expression profile. The invention further provides methods of monitoring differentiation of a cell lineage. These preferred methods entail determining an expression profile of each of a plurality of cells at different differentiation stages within the lineage. These cells can then be classified into clusters determined by similarity of expression profile. The clusters can then be ordered by similarity of expression profile. A time course of expression levels for each of the plurality of genes at different stages of differentiation in the cell lineage can then be determined.

    Abstract translation: 本发明提供监测细胞或细胞群体中多种基因的表达的方法。 优选的方法需要将探针阵列与源自少于1000个细胞的群体的核酸群接触，然后确定探针与核酸群体的相对杂交，作为来自细胞的基因相对表达的量度。 本发明还提供了对细胞进行分类的方法。 这些优选方法需要确定多个细胞中的每一个的细胞的表达谱，然后通过表达谱的相似性确定的簇进行细胞分类。 本发明还提供监测细胞谱系分化的方法。 这些优选的方法需要确定谱系内不同分化阶段的多个细胞中的每一个的表达谱。 然后可以将这些细胞分类为通过表达谱的相似性确定的簇。 然后可以通过表达谱的相似性对簇进行排序。 然后可以确定细胞系中不同分化阶段的多个基因中每个基因的表达水平的时间过程。

    Methods of enzymatic discrimination enhancement and surface bound double-stranded DNA
    35.
    发明申请
    Methods of enzymatic discrimination enhancement and surface bound double-stranded DNA 审中-公开
    酶鉴别增强方法和表面结合双链DNA

    公开(公告)号：US20060292579A1

    公开(公告)日：2006-12-28

    申请号：US11176012

    申请日：2005-07-05

    Applicant: David Lockhart ,  Mark Chee ,  Dirk Vetter ,  Martin Digglemann

    Inventor： David Lockhart ,  Mark Chee ,  Dirk Vetter ,  Martin Digglemann

    IPC: C12Q1/68

    CPC classification number: C12N15/1093 ,  B01J19/0046 ,  B01J2219/00529 ,  B01J2219/00608 ,  B01J2219/00612 ,  B01J2219/00626 ,  B01J2219/0063 ,  B01J2219/00659 ,  B01J2219/00722 ,  C07B2200/11 ,  C07H21/00 ,  C12Q1/6827 ,  C12Q1/683 ,  C12Q1/6837 ,  C12Q1/6874 ,  C40B40/06 ,  C40B80/00 ,  G01N33/5308 ,  G01N33/551

    Abstract: Methods for discriminating between fully complementary hybrids and those that differ by one or more base pairs and libraries of unimolecular, double-stranded oligonucleotides on a solid support. In one embodiment, the present invention provides methods of using nuclease treatment to improve the quality of hybridization signals on high density oligonucleotide arrays. In another embodiment, the present invention provides methods of using ligation reactions to improve the quality of hybridization signals on high density oligonucleotide arrays. In yet another embodiment, the present invention provides libraries of unimolecular or intermolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.

    Abstract translation: 用于区分完全互补的杂交体与通过一个或多个碱基对不同的那些的方法和在固体支持物上的单分子双链寡核苷酸的文库。 在一个实施方案中，本发明提供了使用核酸酶处理来提高高密度寡核苷酸阵列上杂交信号质量的方法。 在另一个实施方案中，本发明提供了使用连接反应来提高高密度寡核苷酸阵列上杂交信号质量的方法。 在另一个实施方案中，本发明提供了在固体支持物上的单分子或分子间双链寡核苷酸的文库。 这些文库在药物发现中可用于筛选许多生物样品，用于双链寡核苷酸与肽，蛋白质，药物和RNA之间的特异性相互作用。 在相关方面，本发明提供了在固体支持物上的构象限制探针的文库。 使用双链寡核苷酸作为脚手架，探针的运动和灵活性受到限制。 探针也可用于与药物发现和诊断相关的各种筛选程序。 本发明还提供了制备和筛选上述文库的方法。

    Complexity management and anaylysis of genomic data
    36.
    发明申请
    Complexity management and anaylysis of genomic data 审中-公开
    基因组数据的复杂性管理和分析

    公开(公告)号：US20060063158A1

    公开(公告)日：2006-03-23

    申请号：US10942364

    申请日：2004-09-16

    Applicant: Shoulian Dong ,  Robert Lipshutz ,  David Lockhart

    Inventor： Shoulian Dong ,  Robert Lipshutz ,  David Lockhart

    IPC: C12Q1/68

    CPC classification number: C12Q1/6837 ,  C12Q1/6855 ,  C12Q1/6858 ,  C12Q2600/156 ,  Y10S977/924 ,  C12Q2531/113 ,  C12Q2525/191 ,  C12Q2521/313 ,  C12Q2563/143

    Abstract: The present invention provides for novel methods of sample preparation and analysis involving reproducibly reducing the complexity of a nucleic sample. The invention further provides for analysis of the above sample by hybridization to an array which may be specifically designed to interrogate the desired fragments for particular characteristics, such as, for example, the presence or absence of a polymorphism. The invention further provides for novel methods of using a computer system to model enzymatic reactions in order to determine experimental conditions before conducting actual experiments.

    Abstract translation: 本发明提供了重复地降低核酸样品的复杂性的样品制备和分析的新方法。 本发明进一步提供了通过与阵列的杂交来分析上述样品，所述阵列可被特别设计成询问特定特征的期望片段，例如多态性的存在或不存在。 本发明进一步提供了使用计算机系统来模拟酶反应以便在进行实际实验之前确定实验条件的新方法。

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