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1. 发明申请

WO2012116331A3 METHODS AND SYSTEMS FOR HAPLOTYPE DETERMINATION 审中-公开
标题翻译：用于HAPLOTYPE测定的方法和系统
公开(公告)号：WO2012116331A3
公开(公告)日：2013-03-07
申请号：PCT/US2012026623
申请日：2012-02-24
申请人： ILLUMINA INC , FAN JIAN-BING , FISHER JEFFREY S , KAPER FIONA
发明人： FAN JIAN-BING , FISHER JEFFREY S , KAPER FIONA
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12Q1/6809 , C12Q1/6827 , C12Q1/6851 , C12Q1/6858 , C12Q2565/50
摘要： Embodiments of the present disclosure provide methods and systems for determining the haplotype of a biological sample. Particular embodiments provide methods for long range haplotyping of a genome.
摘要翻译：本公开的实施方案提供了用于确定生物样品的单体型的方法和系统。具体实施方案提供了用于基因组的长范围单倍型的方法。

2. 发明申请

WO2004007755A9 MULTIPLEX NUCLEIC ACID REACTIONS 审中-公开
标题翻译：多重核酸反应
公开(公告)号：WO2004007755A9
公开(公告)日：2004-05-06
申请号：PCT/US0322171
申请日：2003-07-15
申请人： ILLUMINA INC , CHEE MARK , FAN JIAN-BING , GUNDERSON KEVIN
发明人： CHEE MARK , FAN JIAN-BING , GUNDERSON KEVIN
IPC分类号： C12Q1/68 , C12Q
CPC分类号： C12Q1/6858 , C12Q2563/179 , C12Q2563/149 , C12Q2535/125
摘要： The invention is directed to a variety of multiplexing methods used to amplify and/or genotype a variety of samples simultaneously. The invention provides a method of detecting a target sequence. The method consists of: (a) contacting a first and second probe with a target sequence under conditions where complementary probes form a hybridization complex with the target sequence, the first probe comprising an upstream universal priming site and a target specific sequence, the second probe comprising a downstream universal priming site and a target-specific sequence, wherein one of the first or second probes comprise an adapter sequence; (b) extending the first or second probe of the hybridization complex to form a modified probe; (c) amplifying the modified probe to form an amplicon, and (d) detecting the amplicon. A method of detecting the relative amounts of two or more target sequences is also provided. The method consists of (a) contacting a first and a second probe with first and second target sequences in an initial population under conditions where complementary probes form a hybridization complex with the target sequences, the first and second probes comprising a universal priming site, an adapter sequence and a target-specific sequence; (b) linearly amplifying the first and second probes forming the hybridization complex to produce first and second amplicons having distinctive adapter sequences, and (c) determining a relative amount of the first and second amplicons distinguishable by the adapter sequence, wherein the relative amount of the amplicons is indicative of the relative amounts of the first and second target sequences in the initial population. Further provided is a method of amplifying a target sequence to produce a signal within a dynamic range of a detection assay. The method consists of: (a) hybridizing a target-specific probe having an upstream universal priming site (UUP), a downstream universal priming site (DUP) and an adapter sequence with a set of differential primers, the set of differential primers comprising an upstream primer and first and second downstream primers, the second downstream primer having a lower Tm compared to the upstream primer and the first downstream primer; (b) amplifying the probe with the set of differential primers for two or more cycles of enzymatic polymerization; (c) increasing hybridization stringency to suppress hybridization of the second downstream primer, and (d) amplifying the probe from the upstream and the first downstream primers of the set for at least one cycle of enzymatic polymerization, wherein differential signals of amplicons produced from amplification of the first or the second downstream primers fall within a dynamic range of a detection assay.
摘要翻译：本发明涉及用于同时扩增和/或基因型多种样品的各种复用方法。本发明提供一种检测靶序列的方法。该方法包括：（a）在互补探针与靶序列形成杂交复合物的条件下使第一和第二探针与靶序列接触，第一探针包含上游通用引发位点和靶特异性序列，第二探针包括下游通用引发位点和靶特异性序列，其中所述第一或第二探针中的一个包含衔接子序列; （b）扩增杂交复合物的第一或第二探针以形成修饰的探针; （c）扩增经修饰的探针以形成扩增子，和（d）检测扩增子。还提供了检测两个或多个靶序列的相对量的方法。该方法包括（a）在互补探针与靶序列形成杂交复合物的条件下，在初始群体中使第一和第二探针与第一和第二靶序列接触，第一和第二探针包含通用引发位点，衔接子序列和目标特异性序列; （b）线性扩增形成杂交复合物的第一和第二探针以产生具有不同衔接序列的第一和第二扩增子，和（c）确定由衔接子序列可区分的第一和第二扩增子的相对量，其中相对量扩增子表示初始群体中第一和第二靶序列的相对量。还提供了扩增靶序列以在检测测定的动态范围内产生信号的方法。该方法包括：（a）将具有上游通用引物位点（UUP），下游通用引物位点（DUP）和衔接子序列的靶特异性探针与一组差异引物杂交，所述差异引物组包含上游引物和第一和第二下游引物，所述第二下游引物与上游引物和第一下游引物相比具有较低的Tm; （b）用该组差异引物扩增探针两个或多个酶促聚合循环; （c）增加杂交严格性以抑制第二下游引物的杂交，和（d）从酶的聚合的至少一个循环的上游和第一个下游引物扩增探针，其中扩增产生的扩增子的差异信号的第一或第二下游引物落在检测测定的动态范围内。

3. 发明申请

WO2007050777A3 METHODS AND COMPOSITIONS FOR DIAGNOSING LUNG CANCER WITH SPECIFIC DNA METHYLATION PATTERNS 审中-公开
标题翻译：用特异性DNA甲基化模式诊断肺癌的方法和组合物
公开(公告)号：WO2007050777A3
公开(公告)日：2008-02-14
申请号：PCT/US2006041821
申请日：2006-10-25
申请人： ILLUMINA INC , FAN JIAN-BING , BIBIKOVA MARINA
发明人： FAN JIAN-BING , BIBIKOVA MARINA
IPC分类号： G01N33/48
CPC分类号： C12Q1/6827 , C12Q1/6886 , C12Q2600/112 , C12Q2600/118 , C12Q2600/154 , C12Q2600/16 , C12Q2523/125
摘要： The present invention provides a method for identification of differentially methylated genomic CpG dinucleotide sequences within genomic target sequences that are associated with cancer in an individual by obtaining a biological sample comprising genomic DNA from the individual measuring the level or pattern of methylated genomic CpG dinucleotide sequences for two or more of the genomic targets in the sample, and comparing the level of methylated genomic CpG dinucleotide sequences in the sample to a reference level of methylated genomic CpG dinucleotide sequences, wherein a difference in the level or pattern of methylation of the genomic CpG dinucleotide sequences in the sample compared to the reference level identifies differentially methylated genomic CpG dinucleotide sequences associated with cancer. As disclosed herein, the methods of the invention have numerous diagnostic and prognostic applications. The methods of the invention can be combined with a miniaturized array platform that allows for a high level of assay multiplexing and scalable automation for sample handling and data processing. Also provided by the invention are genomic targets and corresponding nucleic acid probes that are useful in the methods of the invention as they enable detection of differentially methylated genomic CpG dinucleotide sequences associated with adenocarcenomas of the lung.
摘要翻译：本发明提供了通过获得包含来自个体的基因组DNA的生物样品来鉴定与个体癌症相关的基因组靶序列内的差异甲基化基因组CpG二核苷酸序列的方法，所述生物样品包含测量甲基化基因组CpG二核苷酸序列的水平或模式，样品中的两个或更多个基因组靶标，并将样品中甲基化的基因组CpG二核苷酸序列的水平与甲基化的基因组CpG二核苷酸序列的参考水平进行比较，其中基因组CpG二核苷酸的甲基化水平或模式的差异与参考水平相比，样品中的序列鉴定与癌症相关的差异甲基化的基因组CpG二核苷酸序列。如本文所公开的，本发明的方法具有许多诊断和预后应用。本发明的方法可以与微型阵列平台组合，其允许用于样品处理和数据处理的高水平的测定复用和可扩展的自动化。本发明还提供了可用于本发明方法的基因组靶和相应的核酸探针，因为它们能够检测与肺腺癌有关的差异甲基化的基因组CpG二核苷酸序列。

4. 发明申请

WO2004110246A3 METHODS AND COMPOSITIONS FOR DIAGNOSING CONDITIONS ASSOCIATED WITH SPECIFIC DNA METHYLATION PATTERNS 审中-公开
标题翻译：用于特异性DNA甲基化模式诊断条件的方法和组合
公开(公告)号：WO2004110246A3
公开(公告)日：2005-06-09
申请号：PCT/US2004015382
申请日：2004-05-14
申请人： ILLUMINA INC , FAN JIAN-BING , BIBIKOVA MARINA
发明人： FAN JIAN-BING , BIBIKOVA MARINA
IPC分类号： A61B20060101 , C07H21/04 , C12Q1/68 , G01N33/48 , G01N33/50 , G06F19/00
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/154
摘要： The present invention provides a method for identification of differentially methylated genomic CpG dinucleotide sequences associated with cancer in an individual by obtaining a biological sample comprising genomic DNA from the individual measuring the level or pattern of methylated genomic CpG dinucleotide sequences for two or more of the genomic targets in the sample, and comparing the level of methylated genomic CpG dinucleotide sequences in the sample to a reference level of methylated genomic CpG dinucleotide sequences, wherein a difference in the level or pattern of methylation of the genomic CpG dinucleotide sequences in the sample compared to the reference level identifies differentially methylated genomic CpG dinucleotide sequences associated with cancer. As disclosed herein, the methods of the invention have numerous diagnostic and prognostic applications. The methods of the invention can be combined with a miniaturized array platform that allows for a high level of assay multiplexing and scalable automation for sample handling and data processing. Also provided by the invention are genomic targets and corresponding nucleic acid probes that are useful in the methods of the invention as they enable detection of differentially methylated genomic CpG dinucleotide sequences associated with cancer, for example, adenocarcenomas and sqamous cell carcinomas of the lung.
摘要翻译：本发明提供了通过获得包含来自个体的基因组DNA的生物学样品来鉴定与个体相关的癌症的差异甲基化的基因组CpG二核苷酸序列的方法，所述基因组DNA测量两个或多个基因组的甲基化基因组CpG二核苷酸序列的水平或模式样本中的靶标，并将样品中甲基化基因组CpG二核苷酸序列的水平与甲基化基因组CpG二核苷酸序列的参考水平进行比较，其中样品中基因组CpG二核苷酸序列的甲基化水平或模式差异与参考水平鉴定与癌症相关的差异甲基化的基因组CpG二核苷酸序列。如本文所公开的，本发明的方法具有许多诊断和预后应用。本发明的方法可以与微型阵列平台组合，其允许用于样品处理和数据处理的高水平的测定复用和可扩展的自动化。本发明还提供了可用于本发明方法的基因组靶标和相应的核酸探针，因为它们能够检测与癌症相关的差异甲基化的基因组CpG二核苷酸序列，例如肺腺癌细胞癌和鳞状细胞癌。

5. 发明申请

WO2004001062A2 MULTIPLEX NUCLEIC ACID REACTIONS 审中-公开
标题翻译：多重核酸反应
公开(公告)号：WO2004001062A2
公开(公告)日：2003-12-31
申请号：PCT/US0319680
申请日：2003-06-20
申请人： ILLUMINA INC , SHEN MIN-JUI RICHARD , OLIPHANT ARNOLD , BUTLER SCOTT L , STUELPNAGEL JOHN R , CHEE MARK S , KUHN KENNETH M , FAN JIAN-BING
发明人： SHEN MIN-JUI RICHARD , OLIPHANT ARNOLD , BUTLER SCOTT L , STUELPNAGEL JOHN R , CHEE MARK S , KUHN KENNETH M , FAN JIAN-BING
IPC分类号： C12P19/34 , C12Q1/68 , C12Q
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q2535/125 , C12Q2537/143 , C12Q2561/125 , C12Q2565/515
摘要： The invention is directed to a variety of multiplexing methods used to amplify and/or genotype a variety of samples simultaneously.
摘要翻译：本发明涉及用于同时扩增和/或基因型多种样品的多种多样化方法。

6. 发明申请

WO2012135635A3 OVARIAN CANCER BIOMARKERS 审中-公开
标题翻译： OVARIAN癌症生物标志物
公开(公告)号：WO2012135635A3
公开(公告)日：2013-03-07
申请号：PCT/US2012031484
申请日：2012-03-30
申请人： ILLUMINA INC , MAYO FOUNDATION , FAN JIAN-BING , GROCOCK RUSSELL , CHEETHAM KEIRA , SHAW RICHARD , CHIEN JEREMY R , SHRIDHAR VIJAYALAKSHMI , HARTMANN LYNN , EVERS DIRK , PEDEN JOHN
发明人： FAN JIAN-BING , GROCOCK RUSSELL , CHEETHAM KEIRA , SHAW RICHARD , CHIEN JEREMY R , SHRIDHAR VIJAYALAKSHMI , HARTMANN LYNN , EVERS DIRK , PEDEN JOHN
IPC分类号： C12Q1/68 , C12N15/12
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： The present disclosure provides biomarkers and methods of their use in determining the presence or absence of cancer. In preferred embodiments, biomarkers and methods of their use determine the presence or absence of ovarian cancer, a type of ovarian cancer and/or a stage of ovarian cancer in a sample from an individual.
摘要翻译：本公开提供了它们用于确定癌症存在或不存在的生物标志物和方法。在优选的实施方案中，其使用的生物标志物及其方法确定来自个体的样品中是否存在卵巢癌，卵巢癌的类型和/或卵巢癌的阶段。

7. 发明申请

WO2004051224A2 MULTIPLEXED METHYLATION DETECTION METHODS 审中-公开
标题翻译：多相甲基化检测方法
公开(公告)号：WO2004051224A2
公开(公告)日：2004-06-17
申请号：PCT/US0338582
申请日：2003-12-03
申请人： ILLUMINA INC , FAN JIAN-BING
发明人： FAN JIAN-BING
IPC分类号： C12Q1/68 , G01N20060101 , G01N
CPC分类号： C12Q1/6827 , C12Q2537/143 , C12Q2521/331 , C12Q2565/518 , C12Q2523/125 , C12Q2565/501
摘要： The present invention is directed to sensitive and accurate multiplexed assays for target analyte detection and detection of methylation in nucleic acid samples.
摘要翻译：本发明涉及用于目标分析物检测和核酸样品中甲基化检测的敏感且准确的多重测定。

8. 发明申请

WO2011071923A3 MULTI-SAMPLE INDEXING FOR MULTIPLEX GENOTYPING 审中-公开
标题翻译：多重基因多样性指数
公开(公告)号：WO2011071923A3
公开(公告)日：2011-10-20
申请号：PCT/US2010059286
申请日：2010-12-07
申请人： ILLUMINA INC , FAN JIAN-BING , GUNDERSON KEVIN
发明人： FAN JIAN-BING , GUNDERSON KEVIN
IPC分类号： C12Q1/68 , C12N15/11 , G01N33/50
CPC分类号： C12N15/1065 , C12Q1/6816 , C12Q1/6827 , C12Q2521/501 , C12Q2525/155 , C12Q2533/101 , C12Q2533/107 , C12Q2537/143 , C12Q2563/179 , C12Q2565/102 , C12Q2525/186
摘要： A method for determining the presence of multiple nucleotide sequences of interest in multiple samples while preserving the identity of each sample, by contacting the samples with a plurality of probe sets. The probes are designed to indicate the presence of the sequences of interest and the identity of the sample containing the sequence of interest in complex mixtures. Applications of the method include genotyping, expression analysis, and identification of individual species in complex samples. Kits of probe sets for use in the methods are also provided
摘要翻译：通过使样本与多个探针组接触，确定多个样品中多个核苷酸序列的存在同时保持每个样品的身份的方法。探针被设计为指示感兴趣的序列的存在和在复杂混合物中含有感兴趣的序列的样品的身份。该方法的应用包括基因分型，表达分析和复杂样本中个体物种的鉴定。还提供了用于方法的探针组的套件

9. 发明申请

WO02101358A9 MULTIPLEXED DETECTION METHODS 审中-公开
标题翻译：多重检测方法
公开(公告)号：WO02101358A9
公开(公告)日：2003-03-27
申请号：PCT/US0218634
申请日：2002-06-11
申请人： ILLUMINA INC , FAN JIAN-BING , STUELPNAGEL JOHN R , CHEE MARK S
发明人： FAN JIAN-BING , STUELPNAGEL JOHN R , CHEE MARK S
IPC分类号： C12Q1/68 , G01N
CPC分类号： C12Q1/6809 , C12Q2563/179 , C12Q2525/15
摘要： The present invention permits highly multiplexed detection of target molecules in a sample. The method includes contacting target analytes with a composition comprising an amplification enzyme and first and second target probes. The first and second target probes comprise first and second bioactive agent respectively, that specifically bind to the first and second target molecules. The probes may also comprise first and second adapter sequences, respectively, such and that the first adapter sequence identifies the first target molecule and the second adapter sequence identifies the second target molecule, and first and section upstream universal priming sequences, respectively. Finally, following amplification the method includes detecting the first and second amplicons, whereby the first and second target molecules, respectively are detected.
摘要翻译：本发明允许样品中靶分子的高度多重检测。该方法包括使目标分析物与包含扩增酶和第一和第二靶标探针的组合物接触。第一和第二靶探针分别包含特异性结合第一和第二靶分子的第一和第二生物活性剂。探针还可以分别包含第一和第二衔接子序列，并且第一衔接子序列分别标识第一靶分子，第二衔接子序列分别标识第二靶分子以及第一和部分上游通用引物序列。最后，扩增后，该方法包括检测第一和第二扩增子，由此分别检测第一和第二靶分子。

10. 发明申请

WO2012167112A2 GASTRIC CANCER BIOMARKERS 审中-公开
标题翻译：胃癌生物标志物
公开(公告)号：WO2012167112A2
公开(公告)日：2012-12-06
申请号：PCT/US2012040501
申请日：2012-06-01
申请人： ILLUMINA INC , UNIV SINGAPORE , GROCOCK RUSSELL , SOONG RICHIE CHUAN TECK , BECQ JENNIFER , FAN JIAN-BING , MACARTHUR STEWART , CHEETHAM KEIRA , SILVENTOINEN VILLE , EVERS DIRK , WU MENGCHU , YEOH KHAY GUAN , SO BOK YAN JIMMY , TAN BOON OOI PATRICK
发明人： GROCOCK RUSSELL , SOONG RICHIE CHUAN TECK , BECQ JENNIFER , FAN JIAN-BING , MACARTHUR STEWART , CHEETHAM KEIRA , SILVENTOINEN VILLE , EVERS DIRK , WU MENGCHU , YEOH KHAY GUAN , SO BOK YAN JIMMY , TAN BOON OOI PATRICK
IPC分类号： C12Q1/68 , G01N33/574
CPC分类号： C12Q1/6886 , C12Q2600/156 , G01N33/57446
摘要： The present disclosure provides biomarkers and methods of their use in determining the presence or absence of gastric cancer. In preferred embodiments, biomarkers identified comprise mutational hot spots which can be correlated with the presence of gastric cancer in a sample from an individual.
摘要翻译：本公开提供了其用于确定胃癌存在或不存在的生物标志物及其方法。在优选的实施方案中，鉴定的生物标志物包括可与来自个体的样品中胃癌存在相关的突变性热点。

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