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1. 发明申请

WO2004007755A3 MULTIPLEX NUCLEIC ACID REACTIONS 审中-公开
公开(公告)号：WO2004007755A3
公开(公告)日：2004-01-22
申请号：PCT/US2003/022171
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
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.

2. 发明申请

WO2011071923A2 MULTI-SAMPLE INDEXING FOR MULTIPLEX GENOTYPING 审中-公开
标题翻译：用于多重基因分型的多样本索引
公开(公告)号：WO2011071923A2
公开(公告)日：2011-06-16
申请号：PCT/US2010/059286
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：通过使样品与多个探针组接触来确定在多个样品中存在多个核苷酸序列的同时保留每个样品的同一性的方法。探针被设计成指示感兴趣的序列的存在以及复杂混合物中含有感兴趣序列的样本的身份。该方法的应用包括基因分型，表达分析和复杂样品中个体物种的鉴定。还提供了用于该方法的探针组套件

3. 发明申请

WO2003048732A3 MULTIPLEXED METHYLATION DETECTION METHODS 审中-公开
公开(公告)号：WO2003048732A3
公开(公告)日：2003-06-12
申请号：PCT/US2002/038672
申请日：2002-12-03
申请人： ILLUMINA, INC. , FAN, Jian-Bing
发明人： FAN, Jian-Bing
IPC分类号： C12Q1/68
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.

4. 发明申请

WO2012135635A2 OVARIAN CANCER BIOMARKERS 审中-公开
标题翻译： OVARIAN癌症生物标志物
公开(公告)号：WO2012135635A2
公开(公告)日：2012-10-04
申请号：PCT/US2012/031484
申请日：2012-03-30
申请人： ILLUMINA, INC. , MAYO FOUNDATION FOR MEDICAL EDUCATION AND RESEARCH , 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
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。

5. 发明申请

WO2012116331A2 METHODS AND SYSTEMS FOR HAPLOTYPE DETERMINATION 审中-公开
标题翻译： HAPLOTYPE测定的方法和系统
公开(公告)号：WO2012116331A2
公开(公告)日：2012-08-30
申请号：PCT/US2012/026623
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
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距离单倍型的方法。

6. 发明申请

WO2007050777A2 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：WO2007050777A2
公开(公告)日：2007-05-03
申请号：PCT/US2006/041821
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： C12Q1/68 , G06F19/00
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。

7. 发明申请

WO2004110246A2 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：WO2004110246A2
公开(公告)日：2004-12-23
申请号：PCT/US2004/015382
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： A61B
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。

8. 发明申请

WO2004001062A3 MULTIPLEX NUCLEIC ACID REACTIONS 审中-公开
公开(公告)号：WO2004001062A3
公开(公告)日：2003-12-31
申请号：PCT/US2003/019680
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
摘要： The invention is directed to a variety of multiplexing methods used to amplify and/or genotype a variety of samples simultaneously.

9. 发明申请

WO2002101358A2 MULTIPLEXED DETECTION METHODS 审中-公开
标题翻译：多重检测方法
公开(公告)号：WO2002101358A2
公开(公告)日：2002-12-19
申请号：PCT/US2002/018634
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： G01N
CPC分类号： C12Q1/6809 , C12Q2563/179 , C12Q2525/15
摘要： The present invention is directed to sensitive and accurate multiplexed assays for target analyte detection.
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。

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