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公开(公告)号：US08133667B2
公开(公告)日：2012-03-13
申请号：US12272370
申请日：2008-11-17
Applicant: Michael H. Shapero , Keith W. Jones
Inventor： Michael H. Shapero , Keith W. Jones
CPC classification number: C12Q1/683
Abstract: The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by fragmenting the nucleic acid sample with a restriction enzyme that has at least one variable position in the recognition sequence. In some aspects adaptors that ligate to some but not all possible overhangs generated by digestion are ligated to the fragments. This selective adaptor ligation allows for selective amplification of a subset of the fragments using primers complementary to the adaptor sequence. In another aspect primers that are complementary to a subset of the fragments after adaptor ligation are used for amplification. Amplified fragments may be analyzed to genotype polymorphisms by hybridization to an array of probes that are complementary to target sequences that will be amplified.
Abstract translation: 本发明提供降低核酸样品复杂性以询问靶序列集合的方法。 可以通过在识别序列中具有至少一个可变位置的限制酶片段化核酸样品来实现复杂性降低。 在一些方面，连接到通过消化产生的一些但不是所有可能的突出端的衔接子被连接到片段。 该选择性衔接子连接允许使用与衔接子序列互补的引物选择性扩增片段的一个子集。 另一方面，在衔接子连接后与片段的子集互补的引物用于扩增。 可以通过与将被扩增的靶序列互补的探针阵列杂交来分析扩增片段以基因型多态性。
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公开(公告)号：US08114978B2
公开(公告)日：2012-02-14
申请号：US12326596
申请日：2008-12-02
Applicant: Keith W. Jones , Michael H. Shapero , Stephen P. A. Fodor
Inventor： Keith W. Jones , Michael H. Shapero , Stephen P. A. Fodor
CPC classification number: C12Q1/6827 , C12Q1/6809 , C12Q1/6837 , C12Q1/6855 , C12Q2600/156
Abstract: Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some bases that are identical in each sequence in the plurality of sequences and positions that vary from one locus specific region to another. The sequences are selected based on proximity to a polymorphism of interest and because they conform to a similar sequence pattern.
Abstract translation: 描述使用与选定多态性附近的区域互补的位点特异性引物进行基因分型多态性的方法。 还公开了合并含有一些退化位置的基因座特异性引物库的方法。 使用简并寡核苷酸合成同时合成多个不同的序列捕获探针。 捕获探针的基因座特异性区域的序列是相关的，因为它们具有在从一个基因座特异性区域到另一个基因座特异性区域变化的多个序列和位置中的每个序列中具有相同的一些碱基。 基于与感兴趣的多态性的接近度并且因为它们符合类似的序列模式来选择序列。
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公开(公告)号：US07634363B2
公开(公告)日：2009-12-15
申请号：US11608233
申请日：2006-12-07
Applicant: Jing Huang , Keith W. Jones
Inventor： Jing Huang , Keith W. Jones
CPC classification number: G06F19/18 , C12Q2600/156
Abstract: Methods for genotyping polymorphisms using allele specific probes are disclosed. A training set is used to generate a model for each polymorphism to be interrogated. The training set is used to obtain an estimate of the asymmetry between an intensity measurement for a first allele and an intensity measurement for a second allele of the same polymorphism. The intensity measurement obtained for a test sample is adjusted using the estimate of asymmetry prior to using the intensity measurements to make a genotyping call. In preferred embodiments the adjustment is applied to polymorphisms that have a likelihood of being heterozygous that is above a specified threshold.
Abstract translation: 公开了使用等位基因特异性探针进行基因分型多态性的方法。 训练集用于生成要查询的每个多态性的模型。 训练集用于获得第一等位基因的强度测量与相同多态性的第二等位基因的强度测量之间的不对称性的估计。 在使用强度测量进行基因分型调用之前，使用不对称估计来调整测试样品获得的强度测量值。 在优选实施方案中，调整适用于具有高于特定阈值的杂合可能性的多态性。
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公开(公告)号：US07452671B2
公开(公告)日：2008-11-18
申请号：US11381125
申请日：2006-05-01
Applicant: Michael H. Shapero , Keith W. Jones
Inventor： Michael H. Shapero , Keith W. Jones
CPC classification number: C12Q1/683
Abstract: The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by fragmenting the nucleic acid sample with a restriction enzyme that has at least one variable position in the recognition sequence. In some aspects adaptors that ligate to some but not all possible overhangs generated by digestion are ligated to the fragments. Selective adaptor ligation allows for selective amplification of a subset of the fragments using primers complementary to the adaptor sequence. In another aspect primers that are complementary to a subset of the fragments after adaptor ligation are used for amplification. Reduced complexity samples generated by the disclosed methods may be interrogated for the genotypes of SNPs in the sample.
Abstract translation: 本发明提供降低核酸样品复杂性以询问靶序列集合的方法。 可以通过在识别序列中具有至少一个可变位置的限制酶片段化核酸样品来实现复杂性降低。 在一些方面，连接到通过消化产生的一些但不是所有可能的突出端的衔接子被连接到片段。 选择性衔接子连接允许使用与衔接子序列互补的引物选择性扩增片段的一个子集。 另一方面，在衔接子连接后与片段的子集互补的引物用于扩增。 可以询问由所公开的方法产生的降低的复杂度样品用于样品中SNP的基因型。
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公开(公告)号：US4129621A
公开(公告)日：1978-12-12
申请号：US835425
申请日：1977-09-21
Applicant: Wilfred Jones , Keith W. Jones , Travers F. Sweatman
Inventor： Wilfred Jones , Keith W. Jones , Travers F. Sweatman
CPC classification number: B01F3/022 , A61M16/18 , Y10S261/65 , Y10T137/1963 , Y10T137/86743
Abstract: A volatile anesthetic vaporizing apparatus including a concentration control flow valve means actuated by a substantially linear rotary dial for dividing an inflowing gas stream into two separate streams, one stream being passed over liquid anesthetic to pick up a vapor and the other stream flowing through a bypass duct. The gas stream flowing over liquid anesthetic flows through a temperature responsive valve means, the latter being actuated by a temperature sensitive bimetallic strip which is in direct contact with the vapor saturated air stream which is relatively cool due to the vaporization of the liquid anesthetic. The valve means so situated in the vapor stream essentially does not include any moving parts. Such valve means is formed by the spaced mounting of a planar valve element on a planar surface having a vapor opening therein or an inlet passage. The planar valve element has a portion of material removed therefrom and being in contact with a bimetallic strip tends to pivot about the removed portion thereof in response to temperature changes in the vapor saturated stream flow. Such a valve structure avoids problems of sticking, provides substantially laminar flow therethrough and automatically compensates for changes in the temperature of vapor saturated air stream as it leaves the vaporizing chamber apparatus once the volumetric anesthetic percentage has been set on the aforesaid rotary dial to maintain such percentage concentration constant over a substantial temperature range.
Abstract translation: 一种挥发性麻醉剂蒸发装置，包括浓度控制流动阀装置，其由基本上线性的旋转盘驱动，用于将流入的气流分成两个分开的流，一个流经过液体麻醉剂以吸收蒸气，另一个流流过旁路 管。 流过液体麻醉剂的气流流过温度响应阀装置，后者由温度敏感的双金属条驱动，温度敏感的双金属条与由于液体麻醉剂蒸发而相对冷却的蒸气饱和空气流直接接触。 位于蒸汽流中的阀装置基本上不包括任何运动部件。 这种阀装置通过平面阀元件在其中具有蒸气开口的平面表面或入口通道间隔开地安装而形成。 平面阀元件具有从其中去除并与双金属条接触的材料的一部分倾向于响应于蒸汽饱和流流中的温度变化绕其去除的部分枢转。 这样的阀结构避免了粘附问题，提供了大体上的层流，并且一旦将体积麻醉百分比设定在上述旋转盘上，就自动补偿蒸气饱和空气流离开蒸发室设备时的温度变化，以保持这样的 在相当温度范围内的百分比浓度常数。
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Patent Agency Ranking
公开(公告)号：US20130017966A1
公开(公告)日：2013-01-17
申请号：US13365825
申请日：2012-02-03
Applicant: Michael H. Shapero , Keith W. Jones
Inventor： Michael H. Shapero , Keith W. Jones
CPC classification number: C12Q1/683
Abstract: The present invention provides methods for reducing the complexity of a nucleic acid sample to interrogate a collection of target sequences. Complexity reduction can be accomplished by fragmenting the nucleic acid sample with a restriction enzyme that has at least one variable position in the recognition sequence. In some aspects adaptors that ligate to some but not all possible overhangs generated by digestion are ligated to the fragments. This selective adaptor ligation allows for selective amplification of a subset of the fragments using primers complementary to the adaptor sequence. In another aspect primers that are complementary to a subset of the fragments after adaptor ligation are used for amplification. Amplified fragments may be analyzed to genotype polymorphisms by hybridization to an array of probes that are complementary to target sequences that will be amplified.
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公开(公告)号：US07822555B2
公开(公告)日：2010-10-26
申请号：US11295225
申请日：2005-12-05
Applicant: Jing Huang , Keith W. Jones , Michael H. Shapero
Inventor： Jing Huang , Keith W. Jones , Michael H. Shapero
IPC: G06F7/00
CPC classification number: G06F19/18 , C12Q1/6827 , C12Q1/6837 , G06F19/20 , C12Q2545/101
Abstract: Methods of identifying allele-specific changes in genomic DNA copy number are disclosed. Methods for identifying homozygous deletions and genetic amplifications are disclosed. An array of probes designed to detect presence or absence of a plurality of different sequences is also disclosed. The probes are designed to hybridize to sequences that are predicted to be present in a reduced complexity sample. The methods may be used to detect copy number changes in cancerous tissue compared to normal tissue. The methods may be used to diagnose cancer and other diseases associated with chromosomal anomalies.
Abstract translation: 公开了确定基因组DNA拷贝数中等位基因特异性变化的方法。 公开了鉴定纯合缺失和遗传扩增的方法。 还公开了一种设计用于检测多个不同序列的存在或不存在的探针阵列。 探针被设计为与预测存在于复杂度降低的样品中的序列杂交。 与正常组织相比，该方法可用于检测癌组织中的拷贝数变化。 该方法可用于诊断与染色体异常相关的癌症和其他疾病。
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公开(公告)号：US20100144542A1
公开(公告)日：2010-06-10
申请号：US12638939
申请日：2009-12-15
Applicant: Jing Huang , Keith W. Jones
Inventor： Jing Huang , Keith W. Jones
CPC classification number: G06F19/18 , C12Q2600/156
Abstract: Methods for genotyping polymorphisms using allele specific probes are disclosed. A training set is used to generate a model for each polymorphism to be interrogated. The training set is used to obtain an estimate of the asymmetry between an intensity measurement for a first allele and an intensity measurement for a second allele of the same polymorphism. The intensity measurement obtained for a test sample is adjusted using the estimate of asymmetry prior to using the intensity measurements to make a genotyping call. In preferred embodiments the adjustment is applied to polymorphisms that have a likelihood of being heterozygous that is above a specified threshold.
Abstract translation: 公开了使用等位基因特异性探针进行基因分型多态性的方法。 训练集用于生成要查询的每个多态性的模型。 训练集用于获得第一等位基因的强度测量与相同多态性的第二等位基因的强度测量之间的不对称性的估计。 在使用强度测量进行基因分型呼叫之前，使用不对称性的估计来调整测试样品获得的强度测量。 在优选实施方案中，调整适用于具有高于特定阈值的杂合可能性的多态性。
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公开(公告)号：US07728576B1
公开(公告)日：2010-06-01
申请号：US10751491
申请日：2004-01-07
Applicant: Keith W. Jones , Christophe Pierre , Steven L. Ceccio , John Judge , Steve Fuchs
Inventor： Keith W. Jones , Christophe Pierre , Steven L. Ceccio , John Judge , Steve Fuchs
CPC classification number: G01R31/2841
Abstract: The traveling wave excitation system phase shifter chassis method and device of the invention is compact, inexpensive, and versatile when compared to customary methods for generating traveling wave excitation signals that would require using an equivalent number of commercial function generators. The method and device of the invention produces up to 56 simultaneous sine waves that are phase shifted with respect to one another.
Abstract translation: 与用于产生需要使用等效数量的商业功能发生器的行波激励信号的常规方法相比，本发明的行波激励系统移相器机箱方法和装置是紧凑的，便宜的和通用的。 本发明的方法和装置产生多达56个相对于彼此相移的同时正弦波。
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公开(公告)号：US07424368B2
公开(公告)日：2008-09-09
申请号：US10712616
申请日：2003-11-12
Applicant: Jing Huang , Keith W Jones , Michael H. Shapero
Inventor： Jing Huang , Keith W Jones , Michael H. Shapero
CPC classification number: G06F19/20 , C12Q1/6827 , C12Q1/6837 , G06F19/18 , C12Q2545/101
Abstract: Methods of estimating genomic DNA copy number are disclosed. Amplified genomic DNA is hybridized to an array of allele specific SNP probes to generate a hybridization pattern. A value, S, is calculated for individual SNPs in the experimental sample, where S is the log of the arithmetic average of the intensities of the perfect match probes for the SNP. S is calculated for the SNP in reference samples that are matched to the experimental sample in genotype. The mean and standard deviation for the S values of the reference samples are calculated and a log intensity difference is calculated by subtracting the mean values for the reference and experimental samples. The copy number of the SNP region is estimated using the difference between the mean for the SNP in the reference samples and the S value for the SNP in the experimental sample in a log-log linear model.
Abstract translation: 公开了估计基因组DNA拷贝数的方法。 扩增的基因组DNA与等位基因特异性SNP探针的阵列杂交以产生杂交模式。 对于实验样品中的单个SNP计算值S，其中S是SNP完美匹配探针的强度的算术平均值的对数。 对于与基因型实验样品匹配的参考样品中的SNP计算S。 计算参考样品的S值的平均值和标准偏差，并通过减去参考和实验样品的平均值计算对数强度差。 使用对数线性模型中的参考样本中的SNP的平均值与实验样品中的SNP的S值之间的差来估计SNP区域的拷贝数。
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