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1. 发明申请

US20120071331A1 INCREASING CONFIDENCE OF ALLELE CALLS WITH MOLECULAR COUNTING 有权
标题翻译：增加对分子计数的可信度的信心
公开(公告)号：US20120071331A1
公开(公告)日：2012-03-22
申请号：US13237124
申请日：2011-09-20
申请人： James Casbon , Sydney Brenner , Robert Osborne , Conrad Lichtenstein
发明人： James Casbon , Sydney Brenner , Robert Osborne , Conrad Lichtenstein
IPC分类号： C40B20/04
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在特定序列分析配置或过程中测序的相同原始样品的相同基因组区域的单个多核苷酸分子数目的方法和组合物。在本发明的这些方面，将简并碱基区（DBR）连接到随后进行测序的起始多核苷酸分子（例如，在进行某些工艺步骤之后，例如扩增和/或富集）。存在于测序运行中的不同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，包括在基因分型应用中允许更高置信等位基因调用确定。

2. 发明授权

US08481292B2 Increasing confidence of allele calls with molecular counting 有权
标题翻译：通过分子计数增加等位基因呼叫的置信度
公开(公告)号：US08481292B2
公开(公告)日：2013-07-09
申请号：US13237124
申请日：2011-09-20
申请人： James Casbon , Sydney Brenner , Robert Osborne , Conrad Lichtenstein , Andreas Claas
发明人： James Casbon , Sydney Brenner , Robert Osborne , Conrad Lichtenstein , Andreas Claas
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04 , C07H21/00
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在特定序列分析配置或过程中测序的相同原始样品的相同基因组区域的单个多核苷酸分子数目的方法和组合物。在本发明的这些方面，将简并碱基区（DBR）连接到随后进行测序的起始多核苷酸分子（例如，在进行某些工艺步骤之后，例如扩增和/或富集）。存在于测序运行中的不同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，包括在基因分型应用中允许更高置信等位基因调用确定。

3. 发明授权

US08298767B2 Compositions and methods for intramolecular nucleic acid rearrangement 有权
标题翻译：分子内核酸重排的组合物和方法
公开(公告)号：US08298767B2
公开(公告)日：2012-10-30
申请号：US13387343
申请日：2010-08-13
申请人： Sydney Brenner , Gi Mikawa , Robert Osborne , Andrew Slatter
发明人： Sydney Brenner , Gi Mikawa , Robert Osborne , Andrew Slatter
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6874 , C12N15/1065 , C12Q1/6806 , C12Q1/6855 , C12Q1/686 , C12Q2563/179 , C12Q2537/143 , C12Q2535/122 , C12Q2525/161 , C12Q2525/155 , C12Q2525/143
摘要： Aspects of the present invention are drawn to processes for moving a region of interest in a polynucleotide from a first position to a second position with regard to a domain within the polynucleotide, also referred to as a “reflex method”. In certain embodiments, the reflex method results in moving a region of interest into functional proximity to specific domain elements present in the polynucleotide (e.g., primer sites and/or MID). Compositions, kits and systems that find use in carrying out the reflex processes described herein are also provided.
摘要翻译：本发明的方面涉及将多核苷酸中的感兴趣区域从第一位置移动到第二位置的方法，该多核苷酸相对于多核苷酸内的结构域也称为反射方法。在某些实施方案中，反射方法导致将感兴趣区域移动到存在于多核苷酸（例如，引物位点和/或MID）中的特定结构域元件的功能接近。还提供了用于实施本文所述的反射过程的组合物，试剂盒和系统。

4. 发明申请

US20120135407A1 Compositions and Methods for Intramolecular Nucleic Acid Rearrangement 有权
标题翻译：分子内核酸重排的组成和方法
公开(公告)号：US20120135407A1
公开(公告)日：2012-05-31
申请号：US13387343
申请日：2010-08-13
申请人： Sydney Brenner , Gi Mikawa , Robert Osborne , Andrew Slatter
发明人： Sydney Brenner , Gi Mikawa , Robert Osborne , Andrew Slatter
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12N15/1065 , C12Q1/6806 , C12Q1/6855 , C12Q1/686 , C12Q2563/179 , C12Q2537/143 , C12Q2535/122 , C12Q2525/161 , C12Q2525/155 , C12Q2525/143
摘要： Aspects of the present invention are drawn to processes for moving a region of interest in a polynucleotide from a first position to a second position with regard to a domain within the polynucleotide, also referred to as a “reflex method”. In certain embodiments, the reflex method results in moving a region of interest into functional proximity to specific domain elements present in the polynucleotide (e.g., primer sites and/or MID). Compositions, kits and systems that find use in carrying out the reflex processes described herein are also provided.
摘要翻译：本发明的方面涉及将多核苷酸中的感兴趣区域从关于多核苷酸内的结构域的第一位置移动至第二位置的方法，也被称为“反射方法”。在某些实施方案中，反射方法导致将感兴趣区域移动到存在于多核苷酸（例如，引物位点和/或MID）中的特定结构域元件的功能接近。还提供了用于实施本文所述的反射过程的组合物，试剂盒和系统。

5. 发明申请

US20130065793A1 Methods and Compositions for Tagging and Identifying Polynucleotides 有权
公开(公告)号：US20130065793A1
公开(公告)日：2013-03-14
申请号：US13466894
申请日：2012-05-08
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C40B40/08
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.

6. 发明授权

US08318433B2 Methods and compositions for tagging and identifying polynucleotides 有权
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：US08318433B2
公开(公告)日：2012-11-27
申请号：US13425215
申请日：2012-03-20
申请人： Sydney Brenner
发明人： Sydney Brenner
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 hybridization of the oligonucleotide tag to its tag complement on an addressable array; or such analysis can be carried out serially by successive hybridizations of labeled word complements.
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的层次）中指示子混合物，多核苷酸经过，而连续的单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，通过寡核苷酸标签与可寻址阵列上的标签补体的杂交; 或者可以通过标记词互补物的连续杂交来连续进行这种分析。

7. 发明申请

US20120277107A1 Methods and Compositions for Tagging and Identifying Polynucleotides 有权
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：US20120277107A1
公开(公告)日：2012-11-01
申请号：US13425215
申请日：2012-03-20
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C40B20/04 , 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 hybridization of the oligonucleotide tag to its tag complement on an addressable array; or such analysis can be carried out serially by successive hybridizations of labeled word complements.
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的层次）中指示子混合物，多核苷酸经过，而连续的单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，通过寡核苷酸标签与可寻址阵列上的标签补体的杂交; 或者可以通过标记词互补物的连续杂交来连续进行这种分析。

8. 发明授权

US08021842B2 Nucleic acid analysis using sequence tokens 有权
标题翻译：使用序列令牌进行核酸分析
公开(公告)号：US08021842B2
公开(公告)日：2011-09-20
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 , 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.
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。

9. 发明申请

US20100136557A1 Methods and Compositions for Isolating Nucleic Acid Sequence Variants 有权
标题翻译：用于分离核酸序列变体的方法和组合物
公开(公告)号：US20100136557A1
公开(公告)日：2010-06-03
申请号：US12615051
申请日：2009-11-09
申请人： Sydney Brenner
发明人： Sydney Brenner
IPC分类号： C12Q1/68 , C12P19/34 , C12P41/00
CPC分类号： C12Q1/6827 , C12Q1/6869 , C12Q2565/537 , C12Q2533/101 , C12Q2525/186 , C12Q2531/119 , C12Q2565/514 , C12Q2535/101
摘要： The invention is drawn to isolating sequence variants of a genetic locus of interest using a modified iterative primer extension method. The nucleic acids analyzed are generally single stranded and have a reference sequence which is used as a basis for performing iterative single nucleotide extension reactions from a hybridized polymerization primer. The iterative polymerization reactions are configured such that polymerization of the strand will continue if the sequence of the nucleic acid being analyzed matches the reference sequence, whereas polymerization will be terminated if the nucleic acid being analyzed does not match the reference sequence. Nucleic acid strands that have mutations can be isolated using a variety of methods and sequenced to determine the precise identity of the mutation/polymorphism. By performing the method on both strands of the nucleic acid being analyzed, virtually all possible mutations can be identified.
摘要翻译：本发明是使用改进的迭代引物延伸方法来分离遗传基因座的序列变体。分析的核酸通常是单链的，并且具有参考序列，其用作从杂交聚合引物进行迭代单核苷酸延伸反应的基础。配置迭代聚合反应，使得如果被分析的核酸序列与参考序列匹配，则链的聚合将持续，而如果所分析的核酸与参考序列不一致则聚合将终止。可以使用多种方法分离具有突变的核酸链，并测序以确定突变/多态性的精确同一性。通过对正在分析的核酸的两条链进行该方法，实际上可以鉴定所有可能的突变。

10. 发明授权

US07635566B2 Methods and compositions for isolating nucleic acid sequence variants 有权
标题翻译：用于分离核酸序列变体的方法和组合物
公开(公告)号：US07635566B2
公开(公告)日：2009-12-22
申请号：US12163571
申请日：2008-06-27
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： C12Q1/6827 , C12Q1/6869 , C12Q2565/537 , C12Q2533/101 , C12Q2525/186 , C12Q2531/119 , C12Q2565/514 , C12Q2535/101
摘要： The invention is drawn to isolating sequence variants of a genetic locus of interest using a modified iterative primer extension method. The nucleic acids analyzed are generally single stranded and have a reference sequence which is used as a basis for performing iterative single nucleotide extension reactions from a hybridized polymerization primer. The iterative polymerization reactions are configured such that polymerization of the strand will continue if the sequence of the nucleic acid being analyzed matches the reference sequence, whereas polymerization will be terminated if the nucleic acid being analyzed does not match the reference sequence. Nucleic acid strands that have mutations can be isolated using a variety of methods and sequenced to determine the precise identity of the mutation/polymorphism. By performing the method on both strands of the nucleic acid being analyzed, virtually all possible mutations can be identified.
摘要翻译：本发明是使用改进的迭代引物延伸方法来分离遗传基因座的序列变体。分析的核酸通常是单链的，并且具有参考序列，其用作从杂交聚合引物进行迭代单核苷酸延伸反应的基础。配置迭代聚合反应，使得如果被分析的核酸序列与参考序列匹配，则链的聚合将持续，而如果所分析的核酸与参考序列不一致则聚合将终止。可以使用多种方法分离具有突变的核酸链，并测序以确定突变/多态性的精确同一性。通过对正在分析的核酸的两条链进行该方法，实际上可以鉴定所有可能的突变。

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