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95 条记录 (耗时 0.064 秒)

    Nucleic acid analysis using sequence tokens
    41.
    发明授权
    Nucleic acid analysis using sequence tokens 有权

    公开(公告)号：US08445205B2

    公开(公告)日：2013-05-21

    申请号：US13211113

    申请日：2011-08-16

    申请人： Sydney Brenner

    发明人： Sydney Brenner

    IPC分类号： C12Q1/68 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04

    CPC分类号： C12Q1/6837 ,  C12Q1/6827 ,  C12Q2563/179 ,  C12Q2537/113 ,  C12Q2525/186

    摘要： The present invention provides methods and compositions for tagging nucleic acid sequence fragments, e.g., a set of nucleic acid sequence fragments from a single genome, with one or more unique members of a collection of oligonucleotide tags, or sequence tokens, which, in turn, can be identified using a variety of readout platforms. As a general rule, a given sequence token is used once and only once in any tag sequence. In addition, the present invention also provides methods for using the sequence tokens to efficiently determine variations in nucleotide sequences in the associated nucleic acid sequence fragments.

    BASE-BY-BASE MUTATION SCREENING
    43.
    发明申请
    BASE-BY-BASE MUTATION SCREENING 审中-公开
    基本的基本移植筛选

    公开(公告)号：US20120245041A1

    公开(公告)日：2012-09-27

    申请号：US13501209

    申请日：2010-10-29

    申请人： Sydney Brenner ,  Gi Mikawa

    发明人： Sydney Brenner ,  Gi Mikawa

    IPC分类号： C40B20/04

    CPC分类号： C12Q1/6827 ,  C12Q1/6858 ,  C12Q2537/1373 ,  C12Q2535/125 ,  C12Q2525/125

    摘要： Aspects of the present invention are drawn to screening assays for isolating polynucleotides having a sequence variation or mutation. Embodiments of the screening assays include generating a population of polynucleotide duplexes having 5′ overhang regions on one strand of the duplex (the “template” or “bottom strand”) followed by isolating polynucleotide duplexes from the mixture that have one or more mismatched base at the 3′ end of the other strand of the duplex (the “test” or “top” strand).

    摘要翻译： 本发明的方面涉及用于分离具有序列变异或突变的多核苷酸的筛选试验。 筛选测定的实施方案包括产生在双链体（“模板”或“底部链”）的一条链上具有5'突出端区域的多核苷酸双链体群体，随后从具有一个或多个错配碱基的混合物中分离多核苷酸双链体 双链的另一条链的3'末端（“测试”或“顶部”链）。

    NUCLEIC ACID ANALYSIS USING SEQUENCE TOKENS
    44.
    发明申请
    NUCLEIC ACID ANALYSIS USING SEQUENCE TOKENS 有权
    使用序列昆虫的核酸分析

    公开(公告)号：US20100216125A1

    公开(公告)日：2010-08-26

    申请号：US12428229

    申请日：2009-04-22

    申请人： Sydney Brenner

    发明人： Sydney Brenner

    IPC分类号： C12Q1/68 ,  C12P19/34 ,  C12M1/34

    CPC分类号： C12Q1/6837 ,  C12Q1/6827 ,  C12Q2563/179 ,  C12Q2537/113 ,  C12Q2525/186

    摘要： The present invention provides methods and compositions for tagging nucleic acid sequence fragments, e.g., a set of nucleic acid sequence fragments from a single genome, with one or more unique members of a collection of oligonucleotide tags, or sequence tokens, which, in turn, can be identified using a variety of readout platforms. As a general rule, a given sequence token is used once and only once in any tag sequence. In addition, the present invention also provides methods for using the sequence tokens to efficiently determine variations in nucleotide sequences in the associated nucleic acid sequence fragments.

    摘要翻译： 本发明提供了用于标记核酸序列片段的方法和组合物，例如，来自单个基因组的一组核酸序列片段，与寡核苷酸标签或序列标记的集合的一个或多个唯一成员， 可以使用各种读出平台来识别。 作为一般规则，给定的序列令牌在任何标签序列中使用一次且仅一次。 此外，本发明还提供了使用序列令牌有效地确定相关核酸序列片段中的核苷酸序列变异的方法。

    Multiplexed analytical platform
    45.
    发明授权
    Multiplexed analytical platform 有权
    复用分析平台

    公开(公告)号：US07365179B2

    公开(公告)日：2008-04-29

    申请号：US10934617

    申请日：2004-09-02

    申请人： Sydney Brenner

    发明人： Sydney Brenner

    IPC分类号： C12N15/11 ,  C07H21/04

    CPC分类号： C12Q1/6837 ,  C12Q2563/179

    摘要： The invention provides a system and reagents for carrying out multiplexed analytical measurements using the hybridization of oligonucleotide tags to addressable solid phase supports to obtain simultaneous readouts from hundreds to tens of thousands of reactions. In one aspect of the invention, analyte interaction moieties, such as oligonucleotide probes, are produced that are each labeled with a unique synthesis tag constructed from a set of two-nucleotide “words.” During or after an assay, the synthesis tags are converted to hybridization tags that are used in the readout step. Hybridization tags are constructed to maximize discrimination in the readout. Hybridization tags of the invention are preferably constructed from oligonucleotide “words” selected from a minimally cross-hybridizing set using combinatorial synthesis techniques. In a further aspect, discrimination in the readout is enhanced by employing hybridization tags that are constructed with words having the “comma-less” property and by minimizing or eliminating extraneous nucleic acids associated with the hybridization tag during a readout step.

    摘要翻译： 本发明提供了一种系统和试剂，用于使用寡核苷酸标签与可寻址固相载体的杂交来进行多重分析测量，以获得从数百到数万个反应的同时读数。 在本发明的一个方面，产生分析物相互作用部分，例如寡核苷酸探针，每个标记有由一组两核苷酸“单词”构成的唯一合成标签。 在测定期间或之后，将合成标签转化为在读出步骤中使用的杂交标签。 构建杂交标签以最大化读出中的区分。 本发明的杂交标签优选由使用组合合成技术的从最小交叉杂交组中选出的寡核苷酸“词”构建。 在另一方面，通过使用由具有“无逗号”性质的词组构成的杂交标签，以及通过在读出步骤期间最小化或消除与杂交标签相关的外来核酸来增强阅读中的鉴别。

    Solid phase selection of differentially expressed genes
    48.
    发明授权
    Solid phase selection of differentially expressed genes 有权
    差异表达基因的固相选择

    公开(公告)号：US06511802B1

    公开(公告)日：2003-01-28

    申请号：US09227694

    申请日：1999-01-08

    申请人： Glenn Albrecht ,  Sydney Brenner ,  Robert B. DuBridge

    发明人： Glenn Albrecht ,  Sydney Brenner ,  Robert B. DuBridge

    IPC分类号： C12Q168

    CPC分类号： C12Q1/6834 ,  C12N15/1096 ,  C12Q1/6809 ,  C12Q2565/518 ,  C12Q2521/313 ,  C12Q2525/191

    摘要： The invention provides a method and materials for monitoring and isolating differentially expressed genes. In accordance with the method of the invention, differently labeled populations of DNAs from sources to be compared are competitively hybridized with reference DNA cloned on solid phase supports, e.g. microparticles, to provide a differential expression library which, in the preferred embodiment, may be manipulated by fluorescence-activated cell sorting (FACS). Monitoring the relative signal intensity of the different fluorescent labels on the microparticles permits quantitative analysis of expression levels relative to the reference DNA. The invention also provides a method for identifying and isolating rare genes. Populations of microparticles having relative signal intensities of interest can be isolated by FACS and the attached DNAs identified by sequencing, such as with massively parallel signature sequencing (MPSS), or with conventional DNA sequencing protocols.

    摘要翻译： 本发明提供了用于监测和分离差异表达基因的方法和材料。 根据本发明的方法，来自待比较来源的不同标记的DNA群体与克隆在固相载体上的参考DNA竞争性杂交，例如， 微粒，以提供在优选实施方案中可以通过荧光激活细胞分选（FACS）操纵的差异表达文库。 监测微粒上不同荧光标记的相对信号强度允许相对于参照DNA的表达水平进行定量分析。 本发明还提供了鉴定和分离稀有基因的方法。 具有感兴趣的相对信号强度的微粒的群体可以通过FACS和通过测序鉴定的所连接的DNA进行分离，例如通过大规模并行签名测序（MPSS）或常规DNA测序方案。

    Measurement of gene expression profiles in toxicity determination
    49.
    发明授权
    Measurement of gene expression profiles in toxicity determination 有权
    毒性测定中基因表达谱的测定

    公开(公告)号：US06228589B1

    公开(公告)日：2001-05-08

    申请号：US09269911

    申请日：2000-02-28

    申请人： Sydney Brenner

    发明人： Sydney Brenner

    IPC分类号： C12Q168

    CPC分类号： C07H21/00 ,  C12N15/1065 ,  C12N15/1072 ,  C40B40/00

    摘要： A method is provided for assessing the toxicity of a compound in a test organism by measuring gene expression profiles of selected tissues. Gene expression profiles are measured by massively parallel signature sequencing of cDNA libraries constructed from mRNA extracted from the selected tissues. Gene expression profiles provide extensive information on the effects of administering a compound to a test organism in both acute toxicity tests and in prolonged and chronic toxicity tests.

    摘要翻译： 提供了一种通过测量所选组织的基因表达谱来评估化合物在测试生物体中的毒性的方法。 通过从所选择的组织提取的mRNA构建的cDNA文库的大规模平行特征测序来测量基因表达谱。 基因表达谱提供了关于在急性毒性试验和长期和慢性毒性试验中给予化合物对测试生物体的作用的广泛信息。

    Kits for DNA sequencing by stepwise ligation and cleavage
    50.
    发明授权
    Kits for DNA sequencing by stepwise ligation and cleavage 失效
    通过逐步连接和切割进行DNA测序的试剂盒

    公开(公告)号：US5831065A

    公开(公告)日：1998-11-03

    申请号：US712011

    申请日：1996-09-11

    申请人： Sydney Brenner

    发明人： Sydney Brenner

    IPC分类号： C12Q1/68 ,  C07H21/04 ,  C12P19/34

    CPC分类号： C12Q1/6869 ,  C12Q1/6862 ,  C12Q1/6874 ,  Y10S435/81

    摘要： The invention provides a method of nucleic acid sequence analysis based on repeated cycles of ligation to and cleavage of probes at the terminus of a target polynucleotide. At each such cycle one or more terminal nucleotides are identified and one or more nucleotides are removed from the end of the target polynucleotide, such that further cycles of ligation and cleavage can take place. At each cycle the target sequence is shortened by one or more nucleotides until the nucleotide sequence of the target polynucleotide is determined. The method obviates electrophoretic separation of similarly sized DNA fragments and eliminates the difficulties associated with the detection and analysis of spatially overlapping bands of DNA fragments in a gel, or like medium. The invention further obviates the need to generate DNA fragments from long single stranded templates with a DNA polymerase.

    摘要翻译： 本发明提供了基于在靶多核苷酸的末端连接和切割探针的重复循环的核酸序列分析方法。 在每个这样的循环中，鉴定一个或多个末端核苷酸并从靶多核苷酸的末端去除一个或多个核苷酸，从而可以进一步进行连接和切割循环。 在每个循环中，靶序列缩短一个或多个核苷酸，直到确定靶多核苷酸的核苷酸序列。 该方法避免了类似大小的DNA片段的电泳分离，并消除了与凝胶或类似培养基中的DNA片段的空间重叠带的检测和分析相关的困难。 本发明进一步避免了用DNA聚合酶从长单链模板产生DNA片段的需要。