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1. 发明申请

US20050100939A1 System and methods for enhancing signal-to-noise ratios of microarray-based measurements 审中-公开
标题翻译：用于增强基于微阵列的测量的信噪比的系统和方法
公开(公告)号：US20050100939A1
公开(公告)日：2005-05-12
申请号：US10943752
申请日：2004-09-17
申请人： Eugeni Namsaraev , George Karlin-Neumann , Malek Faham , Maneesh Jain , Paul Hardenbol , Thomas Willis , Zhiyong Wang
发明人： Eugeni Namsaraev , George Karlin-Neumann , Malek Faham , Maneesh Jain , Paul Hardenbol , Thomas Willis , Zhiyong Wang
IPC分类号： C12Q1/68 , G01N20060101 , G01N33/48 , G01N33/50 , G06F19/00
CPC分类号： C12Q1/6837 , C12Q2563/131
摘要： The present invention provides systems and methods for large-scale genetic measurements by generating from a sample labeled target sequences whose length, orientation, label, and degree of overlap and complementarity are tailored to corresponding end-attached probes of a solid support so that signal-to-noise ratios of measurement from specifically hybridized labeled target sequences are maximized. Systems for implementing methods of the invention include a set of sample-interacting probes to produce amplicons that either each contain a segment of a target polynucleotide or an oligonucleotide tag that corresponds to a segment of a target polynucleotide, one or more solid phase supports that contain a plurality of end-attached probes, and methods of generating from sample-interacting probe amplicons from which labeled target sequences are tailored for hybridization to the solid phase supports, such as microarrays. In one aspect, labeled target sequences and end-attached probe of the solid phase supports comprise oligonucleotide tags and tag complements, respectively, selected from a minimally cross-hybridizing set.
摘要翻译：本发明提供了用于大规模遗传测量的系统和方法，所述系统和方法通过从样品标记的靶序列产生，所述样品标记的靶序列的长度，取向，标记，重叠度和互补度被量化到固体支持物的相应末端附接探针，来自特异性杂交的标记靶序列的测量的信噪比最大化。用于实施本发明方法的系统包括一组样品相互作用探针以产生扩增子，每个扩增子各含有靶多核苷酸片段或对应于靶多核苷酸片段的寡核苷酸标签，一个或多个固相载体含有多个末端连接的探针，以及从样品相互作用的探针扩增子产生的方法，其中标记的靶序列被定制用于与固相支持物例如微阵列杂交。在一个方面，固相载体的标记的靶序列和末端连接的探针分别包含选自最小交叉杂交组的寡核苷酸标签和标签互补物。

2. 发明申请

US20060019304A1 Simultaneous analysis of multiple genomes 审中-公开
标题翻译：同时分析多个基因组
公开(公告)号：US20060019304A1
公开(公告)日：2006-01-26
申请号：US11189486
申请日：2005-07-25
申请人： Paul Hardenbol , George Karlin-Neumann , Thomas Willis , Maneesh Jain , Nicholas Naclerio
发明人： Paul Hardenbol , George Karlin-Neumann , Thomas Willis , Maneesh Jain , Nicholas Naclerio
IPC分类号： C12Q1/68 , G06F19/00
CPC分类号： C12Q1/6837 , C12Q1/6858 , C12Q2537/143 , C12Q2525/161 , C12Q2533/107
摘要： The invention provides methods for multiplexing readouts from multiple hybridization-based assays that each comprise one or more hybridization or annealing steps and one or more enzymatic processing steps. In one aspect, the invention permits simultaneously analysis of a plurality of genomes by separately hybridizing a set of probes with the different genomes to form sets of probe-genome complexes in separate reaction mixtures that are combined and enzymatically treated to form amplifiable probes. From such amplifiable probes, labeled probes are produced so that for each different locus of each different genome there is a unique labeled probe, which are then specifically hybridized to their respective complements on a microarray. In another aspect, labeled oligonucleotide tags are produced from amplifiable probes. The invention is useful in applications of multiplexed hybridization-based assays for measuring characteristics of genomic samples taken from many different individuals. By conducting hybridization steps separately on samples different individuals then combining them for enzymatic processing, one takes advantage of natural reaction rate differences between hybridization reactions and enzymatic reactions to enable analysis of products of multiple assays on a single readout platform.
摘要翻译：本发明提供了用于从多个基于杂交的测定中复用读出的方法，每个测序包含一个或多个杂交或退火步骤和一个或多个酶处理步骤。一方面，本发明允许通过将一组探针与不同基因组分开杂交来同时分析多个基因组，以在组合和酶处理以形成可扩增探针的分开的反应混合物中形成探针 - 基因组复合物组。从这样的可扩增探针中产生标记的探针，使得对于每个不同基因组的每个不同基因座，存在唯一标记的探针，然后在微阵列上与其各自的互补序列特异性杂交。另一方面，标记的寡核苷酸标签由可扩增的探针产生。本发明在多基于杂交的测定用于测量从许多不同个体获取的基因组样品的特征的应用中是有用的。通过分别对样品进行杂交步骤，然后将它们组合用于酶处理，一个利用杂交反应和酶反应之间的天然反应速率差异，以使得能够在单个读出平台上分析多个测定的产物。

3. 发明申请

US20060252060A1 Direct multiplex characterization of genomic DNA 审中-公开
标题翻译：基因组DNA的直接多重表征
公开(公告)号：US20060252060A1
公开(公告)日：2006-11-09
申请号：US11335174
申请日：2006-01-19
申请人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
发明人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.
摘要翻译：本发明涉及复制核酸反应的新方法，包括扩增，检测和基因分型。本发明依赖于在相应靶核酸存在下被环化的前循环探针的使用，被切割，然后扩增。

4. 发明申请

US20070264642A1 Direct multiplex characterization of genomic DNA 审中-公开
标题翻译：基因组DNA的直接多重表征
公开(公告)号：US20070264642A1
公开(公告)日：2007-11-15
申请号：US11480270
申请日：2006-06-30
申请人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
发明人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.
摘要翻译：本发明涉及多重核酸反应的新方法，包括扩增，检测和基因分型。本发明依赖于在相应靶核酸存在下被环化的前循环探针的使用，被切割，然后扩增。

5. 发明申请

US20070178479A1 Direct multiplex characterization of genomic DNA 审中-公开
公开(公告)号：US20070178479A1
公开(公告)日：2007-08-02
申请号：US11335196
申请日：2006-01-19
申请人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
发明人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.

6. 发明申请

US20060275789A1 Direct multiplex characterization of genomic DNA 审中-公开
公开(公告)号：US20060275789A1
公开(公告)日：2006-12-07
申请号：US11335175
申请日：2006-01-19
申请人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
发明人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.

7. 发明申请

US20050026180A1 Direct multiplex characterization of genomic DNA 有权
公开(公告)号：US20050026180A1
公开(公告)日：2005-02-03
申请号：US10826633
申请日：2004-04-15
申请人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
发明人： Thomas Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald Davis
IPC分类号： G01N33/53 , C07H21/02 , C07H21/04 , C12N15/09 , C12P19/34 , C12Q1/48 , C12Q1/68 , G01N33/566
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.

8. 发明授权

US06858412B2 Direct multiplex characterization of genomic DNA 有权
标题翻译：基因组DNA的直接多重表征
公开(公告)号：US06858412B2
公开(公告)日：2005-02-22
申请号：US09999362
申请日：2001-10-24
申请人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
发明人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
IPC分类号： G01N33/53 , C07H21/02 , C07H21/04 , C12N15/09 , C12P19/34 , C12Q1/48 , C12Q1/68 , G01N33/566
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.
摘要翻译：本发明涉及复制核酸反应的新方法，包括扩增，检测和基因分型。本发明依赖于在相应靶核酸存在下被环化的前循环探针的使用，被切割，然后扩增。

9. 发明申请

US20120065091A1 DIRECT MULTIPLEX CHARACTERIZATION OF GENOMIC DNA 有权
标题翻译：基因DNA的直接多重表征
公开(公告)号：US20120065091A1
公开(公告)日：2012-03-15
申请号：US13206120
申请日：2011-08-09
申请人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
发明人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
IPC分类号： C40B30/04 , C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.
摘要翻译：本发明涉及复制核酸反应的新方法，包括扩增，检测和基因分型。本发明依赖于在相应靶核酸存在下被环化的前循环探针的使用，被切割，然后扩增。

10. 发明授权

US07993880B2 Precircle probe nucleic acid amplification methods 有权
标题翻译：前置探针核酸扩增方法
公开(公告)号：US07993880B2
公开(公告)日：2011-08-09
申请号：US12709319
申请日：2010-02-19
申请人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
发明人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
IPC分类号： C12P19/34 , C07H21/02 , C07H21/04 , C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.
摘要翻译：本发明涉及复制核酸反应的新方法，包括扩增，检测和基因分型。本发明依赖于在相应靶核酸存在下被环化的前循环探针的使用，被切割，然后扩增。

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