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1. 发明申请

WO2006099604A3 METHODS AND COMPOSITIONS FOR ASSAY READOUTS ON MULTIPLE ANALYTICAL PLATFORMS 审中-公开
标题翻译：用于多个分析平台测量准备的方法和组合
公开(公告)号：WO2006099604A3
公开(公告)日：2009-04-23
申请号：PCT/US2006009898
申请日：2006-03-16
申请人： COMPASS GENETICS LLC , BRENNER SYDNEY
发明人： BRENNER SYDNEY
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6816 , C12Q1/68 , C12Q2537/143 , C12Q2525/185 , C12Q2525/151 , C12Q2565/125 , C12Q2565/501
摘要： The invention provides methods and compositions for reading out the results of multiplex assays on various analytical platforms, such as microarrays, bead arrays, electrophoresis devices, and the like. An important feature of the invention includes methods for converting different sets of oligonucleotide tags used for labeling into oligonucleotide tags specific for a particular analytical platform. The invention further includes compositions comprising oligonucleotide tags having convenient properties for labeling and conversion, particularly ligation tags that employ ligation reaction specificity as well as sequence specificity in order to discriminate between tags.
摘要翻译：本发明提供用于读出多种分析平台如微阵列，珠阵列，电泳装置等的多重测定结果的方法和组合物。本发明的一个重要特征包括用于将用于标记的不同组的寡核苷酸标签转换成特定于特定分析平台的寡核苷酸标签的方法。本发明还包括包含具有方便的标记和转化性质的寡核苷酸标签的组合物，特别是使用连接反应特异性的连接标签以及序列特异性以区分标签。

2. 发明申请

WO2006086210A3 METHODS AND COMPOSITIONS FOR TAGGING AND IDENTIFYING POLYNUCLEOTIDES 审中-公开
标题翻译：用于标记和鉴定多核苷酸的方法和组合物
公开(公告)号：WO2006086210A3
公开(公告)日：2009-04-16
申请号：PCT/US2006003689
申请日：2006-02-03
申请人： COMPASS GENETICS LLC , BRENNER SYDNEY
发明人： BRENNER SYDNEY
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12N15/1065 , C12N15/1093 , C12P19/34 , C12Q1/6827 , C12Q1/6837 , Y10T436/143333 , C12Q2565/514 , C12Q2563/179 , C12Q2537/143 , C12Q2525/191
摘要： The invention provides methods and compositions for attaching oligonucleotide tags to polynucleotides for the purpose of carrying out analytical assays in parallel and for decoding the oligonucleotide tags of polynucleotides selected in such assays. Words, or subunits, of oligonucleotide tags index submixtures in successively more complex sets of submixtures (referred to herein as "tiers" of submixtures) that a polynucleotide goes through while successive words are added to a growing tag. By identifying each word of an oligonucleotide tag, a series of submixtures is identified including the first submixture that contains only a single polynucleotide, thereby providing the identity of the selected polynucleotide. The analysis of the words of an oligonucleotide tag can be carried out in parallel, e.g. by specific hybridization of the oligonucleotide tag to its tag complement on an addressable array; or such analysis can be carried out serially by successive specific hybridizations of labeled word complements, or the like.
摘要翻译：本发明提供了用于将寡核苷酸标签连接到多核苷酸的方法和组合物，用于并行进行分析测定并解码在这些测定中选择的多核苷酸的寡核苷酸标签。寡核苷酸标签的单词或亚单位在连续更复杂的一组子混合物（本文中称为“子混合物”）中指示子混合物，多核苷酸经过，而连续词被添加到生长标签中。通过鉴定寡核苷酸标签的每个单词，鉴定了一系列的亚混合物，其包括仅包含单个多核苷酸的第一个亚基混合物，从而提供所选多核苷酸的身份。寡核苷酸标签的词的分析可以并行进行，例如，通过在可寻址阵列上寡核苷酸标签与其标签补体的特异性杂交; 或者这样的分析可以通过标记的词互补体的连续特异性杂交等连续进行。

3. 发明申请

WO2007087262A3 SELECTIVE GENOME AMPLIFICATION 审中-公开
标题翻译：选择性基因组扩增
公开(公告)号：WO2007087262A3
公开(公告)日：2007-12-21
申请号：PCT/US2007001679
申请日：2007-01-22
申请人： COMPASS GENETICS LLC , BRENNER SYDNEY , MIKAWA GI , MACEVICZ STEPHEN C
发明人： BRENNER SYDNEY , MIKAWA GI , MACEVICZ STEPHEN C
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6855 , C12P19/34 , C12Q1/6865 , C12Q2525/301 , C12Q2525/143 , C12Q2531/143
摘要： The invention provides methods and compositions for amplifying selected polynucleotides, especially selected subsets of restriction fragments. Generally, methods of the invention are implemented by ligating adaptors containing at least one promoter sequence to such fragments under conditions that promote the formation of closed single stranded or double stranded structures, which are capable of serving as cyclical templates for transcription.
摘要翻译：本发明提供了用于扩增选择的多核苷酸，特别是选定的限制性片段子集的方法和组合物。一般而言，本发明的方法通过在促进形成闭合的单链或双链结构的条件下将含有至少一个启动子序列的衔接子连接到此类片段上来实施，所述闭合的单链或双链结构能够充当用于转录的循环模板。

4. 发明申请

WO2006086209A3 GENETIC ANALYSIS BY SEQUENCE-SPECIFIC SORTING 审中-公开
标题翻译：通过序列特异性分类进行遗传分析
公开(公告)号：WO2006086209A3
公开(公告)日：2007-09-13
申请号：PCT/US2006003688
申请日：2006-02-03
申请人： COMPASS GENETICS LLC , BRENNER SYDNEY
发明人： BRENNER SYDNEY
IPC分类号： C12Q1/68
CPC分类号： C12P19/34
摘要： The invention provides methods for sorting polynucleotides from a population based on predetermined sequence characteristics. In one aspect, the method of the invention is carried out by extending a primer annealed polynucleotides having predetermined sequence characteristics to incorporate a predetermined terminator having a capture moiety, capturing polynucleotides having extended primers by a capture agent that specifically binds to the capture moiety, and melting the captured polynucleotides from the extended primers to form a subpopulation of polynucleotides having the predetermined sequence characteristics. In another aspect, the method of the invention is carried out on a population of tagged polynucleotides so that after a subpopulation is selected, the members of the subpopulation may be simultaneously analyzed using the unique tags on the polynucleotides to convey analytical information to a hybridization array for a readout.
摘要翻译：本发明提供了基于预定序列特征从群体中分选多核苷酸的方法。在一个方面，本发明的方法是通过延长具有预定序列特征的引物退火多核苷酸来引入具有捕获部分的预定终止子，通过特异性结合捕获部分的捕获剂捕获具有延伸引物的多核苷酸，以及从扩展的引物融合捕获的多核苷酸以形成具有预定序列特征的多核苷酸亚群。在另一方面，本发明的方法是对标记的多核苷酸群体进行的，使得在选择亚群后，可以使用多核苷酸上的唯一标签同时分析亚群体的成员，以将分析信息传递到杂交阵列用于读出。

5. 发明申请

WO2005080604A2 GENETIC ANALYSIS BY SEQUENCE-SPECIFIC SORTING 审中-公开
标题翻译：通过序列特异性分类进行遗传分析
公开(公告)号：WO2005080604A2
公开(公告)日：2005-09-01
申请号：PCT/US2005004217
申请日：2005-02-10
申请人： COMPASS GENETICS LLC , BRENNER SYDNEY
发明人： BRENNER SYDNEY
IPC分类号： C12N1/08 , C12P19/34 , C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6834 , C12Q2563/131 , C12Q2525/186 , C12Q2525/161
摘要： The invention provides methods for sorting polynucleotides from a population based on predetermined sequence characteristics. In one aspect, the method of the invention is carried out by extending a primer annealed polynucleotides having predetermined sequence characteristics to incorporate a predetermined terminator having a capture moiety, capturing polynucleotides having extended primers by a capture agent that specifically binds to the capture moiety, and melting the captured polynucleotides from the extended primers to form a subpopulation of polynucleotides having the predetermined sequence characteristics. In another aspect, the method of the invention is carried out on a population of tagged polynucleotides so that after a subpopulation is selected, the members of the subpopulation may be simultaneously analyzed using the unique tags on the polynucleotides to convey analytical information to a hybridization array for a readout.
摘要翻译：本发明提供了基于预定序列特征从群体中分选多核苷酸的方法。在一个方面，本发明的方法是通过延伸具有预定序列特征的引物退火多核苷酸来引入具有捕获部分的预定终止子，通过特异性结合捕获部分的捕获剂捕获具有延伸引物的多核苷酸，以及从扩展的引物融合捕获的多核苷酸以形成具有预定序列特征的多核苷酸亚群。在另一方面，本发明的方法是对标记的多核苷酸群体进行的，使得在选择亚群后，可以使用多核苷酸上的唯一标签同时分析亚群的成员，以将分析信息传递给杂交阵列用于读出。

6. 发明申请

WO2006081222A2 ISOTHERMAL DNA AMPLIFICATION 审中-公开
标题翻译：同位素DNA扩增
公开(公告)号：WO2006081222A2
公开(公告)日：2006-08-03
申请号：PCT/US2006002391
申请日：2006-01-23
申请人： COMPASS GENETICS LLC , BRENNER SYDNEY , MIKAWA GI
发明人： BRENNER SYDNEY , MIKAWA GI
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12P19/34 , C12Q1/6865 , C12Q2565/537 , C12Q2525/301
摘要： The present invention provides for amplification of one or more polynucleotides by multi-staged linear amplifications using one or more RNA polymerases. At each stage RNA transcripts are accumulated at a linear rate, so that multiple stages provide for faster than linear transcript accumulation. In one aspect, the invention provides for polynucleotide amplification by ligating hairpin adaptors to an end of polynucleotides wherein the hairpin adaptors each contain a promoter sequence oriented so that transcription proceeds in the direction of the loop of the hairpin adaptor. Upon transcription through such loop region and to the complementary strand a replicate is made of the promoter sequence as well as the polynucleotide, thereby permitting exponential amplification upon reverse transcription, second strand synthesis, and repetition of the above cycle. Preferably such amplification is carried out under isothermal reaction conditions.
摘要翻译：本发明通过使用一种或多种RNA聚合酶的多级线性扩增来提供一种或多种多核苷酸的扩增。在每个阶段，RNA转录物以线性速率累积，使得多个阶段提供比线性转录物积累更快的阶段。在一个方面，本发明通过将发夹衔接子连接到多核苷酸的末端来提供多核苷酸扩增，其中发夹衔接子各自含有取向的启动子序列，使得转录沿发夹衔接子的环的方向进行。在通过这种环区转录和互补链时，由启动子序列以及多核苷酸重复，从而允许逆转录，第二链合成和上述循环的重复进行指数扩增。优选地，这种扩增在等温反应条件下进行。

7. 发明申请

WO2007087312A2 MOLECULAR COUNTING 审中-公开
标题翻译：分子计数
公开(公告)号：WO2007087312A2
公开(公告)日：2007-08-02
申请号：PCT/US2007001796
申请日：2007-01-22
申请人： COMPASS GENETICS LLC , MACEVICZ STEPHEN C , BRENNER SYDNEY
发明人： BRENNER SYDNEY
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6816 , C12Q2565/125 , C12Q2525/185 , C12Q2525/151 , C12Q2565/501 , C12Q2537/143
摘要： The invention provides methods and compositions for counting molecules in a sample, wherein each molecule is labeled with a unique oligonucleotide tag. Such tags are amplified and identified rather than the molecules themselves; that is, the problem of counting molecules is converted into the problem of counting tags. In one aspect of the invention, molecules to be counted are labeled by sampling. That is, conjugates are formed between the molecules to be counted and oligonucleotide tags of a very large set, or repertoire. After conjugation, a sample of conjugates is taken that is sufficiently small so that substantially every molecule has a unique oligonucleotide tag. Counting of different tags may be accomplished in a variety of ways. In one aspect, different tags may be counted by carrying out a series of sorting steps to generate successively less complex mixtures in which tags are enumerated using length-encoded "metric" tags. In another aspect, different tags may be counted by directly sequencing a sample of tags using any one of several different sequencing methodologies.
摘要翻译：本发明提供了用于计数样品中分子的方法和组合物，其中每个分子用唯一的寡核苷酸标签进行标记。这些标签被扩增和鉴定，而不是分子本身; 也就是说，将分子计数的问题转化为计数标签的问题。在本发明的一个方面，待计数的分子通过取样进行标记。也就是说，在要计数的分子和非常大的集合或所有组成部分的寡核苷酸标签之间形成缀合物。缀合后，取出足够小的缀合物样品，使得基本上每个分子都具有唯一的寡核苷酸标签。不同标签的计数可以以各种方式实现。在一个方面，可以通过执行一系列分类步骤来计算不同的标签，以生成使用长度编码的“度量”标签来枚举标签的连续不太复杂的混合。在另一方面，可以使用几种不同的测序方法中的任何一种直接对标签样品进行排序来计数不同的标签。

8. 发明申请

WO2005026686A2 MULTIPLEXED ANALYTICAL PLATFORM 审中-公开
标题翻译：多重分析平台
公开(公告)号：WO2005026686A2
公开(公告)日：2005-03-24
申请号：PCT/US2004028728
申请日：2004-09-02
申请人： COMPASS GENETICS LLC , BRENNER SYDNEY
发明人： BRENNER SYDNEY
IPC分类号： C12M1/34 , C12Q1/68 , G01N20060101 , G01N
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. hi 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。另一方面，通过使用由具有“无逗号”性质的单词构建的杂交标签并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读出中的鉴别。

9. 发明申请

WO2012038839A2 INCREASING CONFIDENCE OF ALLELE CALLS WITH MOLECULAR COUNTING 审中-公开
标题翻译：利用分子计数提高ALLELE呼叫的信心
公开(公告)号：WO2012038839A2
公开(公告)日：2012-03-29
申请号：PCT/IB2011003160
申请日：2011-09-20
申请人： POPULATION GENETICS TECH LTD , CASBON JAMES , BRENNER SYDNEY , OSBORNE ROBERT , LICHTENSTEIN CONRAD
发明人： CASBON JAMES , BRENNER SYDNEY , OSBORNE ROBERT , LICHTENSTEIN CONRAD
IPC分类号： C12N15/09
CPC分类号： C12Q1/6855 , C12N15/1065 , C12Q1/6869 , C12Q1/6886 , C12Q1/70 , G06F19/18 , C12Q2525/179 , C12Q2525/191 , C12Q2545/101
摘要： Aspects of the present invention include methods and compositions for determining the number of individual polynucleotide molecules originating from the same genomic region of the same original sample that have been sequenced in a particular sequence analysis configuration or process. In these aspects of the invention, a degenerate base region (DBR) is attached to the starting polynucleotide molecules that are subsequently sequenced (e.g., after certain process steps are performed, e.g., amplification and/or enrichment). The number of different DBR sequences present in a sequencing run can be used to determine/estimate the number of different starting polynucleotides that have been sequenced. DBRs can be used to enhance numerous different nucleic acid sequence analysis applications, including allowing higher confidence allele call determinations in genotyping applications.
摘要翻译：本发明的方面包括用于确定源自相同原始样本的相同基因组区域的单个多核苷酸分子的数量的方法和组合物，所述原始样本已经在特定序列分析构造或过程中测序。在本发明的这些方面，将简并碱基区（DBR）连接到随后测序的起始多核苷酸分子上（例如在进行某些处理步骤后，例如扩增和/或富集）。测序运行中存在的不同DBR序列的数目可用于确定/估计已测序的不同起始多核苷酸的数目。 DBR可用于增强许多不同的核酸序列分析应用，包括允许在基因分型应用中进行更高可信度的等位基因呼叫测定。

10. 发明申请

WO2011107887A2 METHODS FOR REPLICATING POLYNUCLEOTIDES WITH SECONDARY STRUCTURE 审中-公开
标题翻译：用二级结构代替多核苷酸的方法
公开(公告)号：WO2011107887A2
公开(公告)日：2011-09-09
申请号：PCT/IB2011000830
申请日：2011-02-28
申请人： POPULATION GENETIC TECHNOLOGIES LTD , BRENNER SYDNEY , OSBORNE ROBERT , SLATTER ANDREW
发明人： BRENNER SYDNEY , OSBORNE ROBERT , SLATTER ANDREW
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6848 , C12Q1/6853 , C12Q2537/143 , C12Q2525/161 , C12Q2525/143
摘要： Aspects of the present invention are drawn to processes for replicating polynucleotide sequences having secondary structure(s) that reduce or inhibit the replication process. Compositions, kits and systems that find use in carrying out the replication processes described herein are also provided.
摘要翻译：本发明的方面涉及用于复制具有减少或抑制复制过程的二级结构的多核苷酸序列的方法。还提供了用于实施本文所述的复制过程的组合物，试剂盒和系统。

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