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公开(公告)号：US5871697A
公开(公告)日：1999-02-16
申请号：US547214
申请日：1995-10-24
CPC分类号： G06F19/24 , C12N15/10 , C12Q1/68 , C12Q1/6809 , C12Q1/6855 , G06F19/22 , Y10S707/99936
摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.
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2.发明授权Method and apparatus for identifying classifying or quantifying DNA sequences in a sample without sequencing 失效用于鉴定样品中DNA序列分类或定量的方法和装置，无需测序
公开(公告)号：US6141657A
公开(公告)日：2000-10-31
申请号：US942406
申请日：1997-10-01
CPC分类号： G06F19/24 , C12N15/10 , C12Q1/68 , C12Q1/6809 , C12Q1/6855 , G06F19/22 , Y10S707/99936
摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.
摘要翻译： 本发明提供了可以确定和分类混合样品或排列单序列克隆中的生物衍生DNA序列而不进行测序的方法。 这些方法利用关于精确选择的目标子序列的存在的信息，通常长度为4至8个碱基对，优选样品DNA序列中目标子序列之间的长度以及含有可能存在的序列的DNA序列数据库 在样品中确定样品序列。 优选的方法是使用限制性核酸内切酶识别目标子序列并切割样品序列。 然后仔细选择识别部分连接到切割片段，扩增片段，并进行实验观察。 聚合酶链反应（PCR）是优选的扩增方法。 本发明的另一个实施方案使用关于在单个序列克隆中与DNA序列数据库一起存在或不存在仔细选择的目标子序列的信息来确定克隆序列。 提供计算机实现的方法来分析实验结果并确定所讨论的样本序列，并仔细选择目标子序列，以便实验产生最大量的信息。
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3.发明授权Method and apparatus for identifying, classifying, or quantifying protein sequences in a sample without sequencing 失效用于在不测序的情况下鉴定，分类或定量样品中蛋白质序列的方法和装置公开(公告)号：US06453245B1
公开(公告)日：2002-09-17
申请号：US09757528
申请日：2001-01-10
IPC分类号： G01N1506
CPC分类号： G06F19/24 , C12N15/10 , C12Q1/68 , C12Q1/6809 , C12Q1/6855 , G06F19/22 , Y10S707/99936
摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.
摘要翻译： 本发明提供了可以确定和分类混合样品或排列单序列克隆中的生物衍生DNA序列而不进行测序的方法。 这些方法利用关于精确选择的目标子序列的存在的信息，通常长度为4至8个碱基对，优选样品DNA序列中目标子序列之间的长度以及含有可能存在的序列的DNA序列数据库 在样品中确定样品序列。 优选的方法是使用限制性核酸内切酶识别目标子序列并切割样品序列。 然后仔细选择识别部分连接到切割片段，扩增片段，并进行实验观察。 聚合酶链反应（PCR）是优选的扩增方法。 本发明的另一个实施方案使用关于在单个序列克隆中与DNA序列数据库一起存在或不存在仔细选择的目标子序列的信息来确定克隆序列。 提供计算机实现的方法来分析实验结果并确定所讨论的样本序列，并仔细选择目标子序列，以便实验产生最大量的信息。
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4.发明授权Method and apparatus for indentifying, classifying, or quantifying protein sequences in a sample without sequencing 失效用于在不测序的情况下对样品中的蛋白质序列进行鉴定，分类或定量的方法和装置公开(公告)号：US06231812B1
公开(公告)日：2001-05-15
申请号：US09322617
申请日：1999-05-28
IPC分类号： G01N1506
CPC分类号： G06F19/24 , C12N15/10 , C12Q1/68 , C12Q1/6809 , C12Q1/6855 , G06F19/22 , Y10S707/99936
摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.
摘要翻译： 本发明提供了可以确定和分类混合样品或排列单序列克隆中的生物衍生DNA序列而不进行测序的方法。 这些方法利用关于精确选择的目标子序列的存在的信息，通常长度为4至8个碱基对，优选样品DNA序列中目标子序列之间的长度以及含有可能存在的序列的DNA序列数据库 在样品中确定样品序列。 优选的方法是使用限制性核酸内切酶识别目标子序列并切割样品序列。 然后仔细选择识别部分连接到切割片段，扩增片段，并进行实验观察。 聚合酶链反应（PCR）是优选的扩增方法。 本发明的另一个实施方案使用关于在单个序列克隆中与DNA序列数据库一起存在或不存在仔细选择的目标子序列的信息来确定克隆序列。 提供计算机实现的方法来分析实验结果并确定所讨论的样本序列，并仔细选择目标子序列，以便实验产生最大量的信息。
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公开(公告)号：US06432361B1
公开(公告)日：2002-08-13
申请号：US09724385
申请日：2000-11-28
IPC分类号： G01N1506
CPC分类号： G06F19/24 , C12N15/10 , C12Q1/68 , C12Q1/6809 , C12Q1/6855 , G06F19/22 , Y10S707/99936
摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.
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6.发明授权Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing 失效用于鉴定，分类或定量样品中DNA序列的方法和设备，无需测序公开(公告)号：US06418382B2
公开(公告)日：2002-07-09
申请号：US09751561
申请日：2000-12-29
IPC分类号： G01N1506
CPC分类号： G06F19/24 , C12N15/10 , C12Q1/68 , C12Q1/6809 , C12Q1/6855 , G06F19/22 , Y10S707/99936
摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.
摘要翻译： 本发明提供了可以确定和分类混合样品或排列单序列克隆中的生物衍生DNA序列而不进行测序的方法。 这些方法利用关于精确选择的目标子序列的存在的信息，通常长度为4至8个碱基对，优选样品DNA序列中目标子序列之间的长度以及含有可能存在的序列的DNA序列数据库 在样品中确定样品序列。 优选的方法是使用限制性核酸内切酶识别目标子序列并切割样品序列。 然后仔细选择识别部分连接到切割片段，扩增片段，并进行实验观察。 聚合酶链反应（PCR）是优选的扩增方法。 本发明的另一个实施方案使用关于在单个序列克隆中与DNA序列数据库一起存在或不存在仔细选择的目标子序列的信息来确定克隆序列。 提供计算机实现的方法来分析实验结果并确定所讨论的样本序列，并仔细选择目标子序列，以便实验产生最大量的信息。
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7.发明授权Apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing 失效用于鉴定，分类或定量样品中DNA序列而不进行测序的装置
公开(公告)号：US5972693A
公开(公告)日：1999-10-26
申请号：US663823
申请日：1996-06-14
IPC分类号： G01N33/50 , C12M1/34 , C12N15/09 , C12N15/10 , C12Q1/68 , G06F17/30 , G06F19/22 , C12M1/00 , G01N1/28 , H01L21/20
CPC分类号： C12Q1/6855 , C12N15/10 , C12N15/1034 , C12Q1/68 , C12Q1/6809 , G06F19/24 , G06F19/22 , Y10S977/728 , Y10S977/924 , Y10T436/143333
摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Several alternative embodiments are described which capable of increased discrimination and which use TypeIIS restriction endonucleases, various capture moieties, or samples of specially synthesized cDNA. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.
摘要翻译： 本发明提供了可以确定和分类混合样品或排列单序列克隆中的生物衍生DNA序列而不进行测序的方法。 这些方法利用关于精确选择的目标子序列的存在的信息，通常长度为4至8个碱基对，优选样品DNA序列中目标子序列之间的长度以及含有可能存在的序列的DNA序列数据库 在样品中确定样品序列。 优选的方法是使用限制性核酸内切酶识别目标子序列并切割样品序列。 然后仔细选择识别部分连接到切割片段，扩增片段，并进行实验观察。 聚合酶链反应（PCR）是优选的扩增方法。 描述了能够增加鉴别和使用TypeIIS限制性内切核酸酶，各种捕获部分或特别合成的cDNA的样品的几种备选实施方案。 本发明的另一个实施方案使用关于在单个序列克隆中与DNA序列数据库一起存在或不存在仔细选择的目标子序列的信息来确定克隆序列。 提供计算机实现的方法来分析实验结果并确定所讨论的样本序列，并仔细选择目标子序列，以便实验产生最大量的信息。
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8.发明授权Consensus configurational bias Monte Carlo method and system for pharmacophore structure determination 失效共同配置偏差蒙特卡罗方法和药效团结构测定系统公开(公告)号：US06341256B1
公开(公告)日：2002-01-22
申请号：US08418992
申请日：1995-03-31
IPC分类号： G06F1900
CPC分类号： G01N33/6803 , B01J2219/007 , C07K1/00 , C40B40/10 , G01N33/542 , G01N33/54326 , G01N33/5748 , Y10S977/808 , Y10S977/839 , Y10S977/906 , Y10S977/953 , Y10T436/24
摘要： In a specific embodiment, this invention includes a method for determining an accurate, consensus pharmacophore structure shared by compounds that bind selectively to a target molecule. Optionally, the method begins with screening a diversity library against the target molecule of interest to pick the selectively binding members. Next the structure of the selected members is examined and a candidate pharmacophore responsible for the binding to the target molecule is determined. Next, preferably by REDOR nuclear magnetic resonance, several highly accurate interatomic distances are determined in certain of the selected members which are related to the candidate pharmacophore. A highly accurate consensus, configurational bias, Monte Carlo method determination of the structure of the candidate pharmacophore is made using the structure of the selected members and incorporating as constraints the shared candidate pharmacophore and the several measured distances. This determination is adapted to efficiently examine only relatively low energy configurations while respecting any structural constraints present in the organic diversity library. If the diversity library contains short peptides, the determination respects the known degrees of freedom of peptides as well as any internal constraints, such as those imposed by disulfide bridges. Finally, the highly accurate pharmacophore so determined is used to select lead organics for drug development targeted at the initial target molecule.
摘要翻译： 在具体实施方案中，本发明包括用于确定由选择性结合靶分子的化合物共享的准确的，一致的药效团结构的方法。 任选地，该方法开始于针对感兴趣的靶分子筛选多样性文库以选择性结合成员。 接下来，检查所选成员的结构，确定负责与靶分子结合的候选药效团。 接下来，优选地通过REDOR核磁共振，在与候选药效团相关的某些选定的成员中确定几个高度准确的原子间距离。 使用所选择的成员的结构并将作为约束的共同候选药效基团和几个测量距离并入，来确定候选药效团的结构的高度准确的共识，构型偏差，蒙特卡罗方法确定候选药效团的结构。 该确定适于在尊重有机分集库中存在的任何结构约束的同时仅有效地检查相对较低的能量构型。 如果多样性文库包含短肽，则确定方面取决于肽的已知自由度以及任何内部约束，例如由二硫键施加的约束。 最后，如此确定的高度精确的药效团用于选择靶向初始靶分子的药物开发的铅有机物。
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公开(公告)号：US06190868B1
公开(公告)日：2001-02-20
申请号：US09381779
申请日：1999-09-23
IPC分类号： C12Q168
CPC分类号： C12N15/1093 , C12Q1/6809 , C12Q1/6813 , C12Q1/6855 , C12Q2525/191 , C12Q2565/125
摘要： The present invention discloses a methodology which is directed to providing positive confirmation that nucleic acids, possessing putatively identified sequence predicted to generate observed GeneCalling™ signals, are actually present within the sample from which the signal was originally derived. The putatively identified nucleic acid fragment within the sample possesses 3′- and 5′-ends with known terminal subsequences, said method comprising; contacting said nucleic acid fragments in said sample in amplifying conditions with (i) a nucleic acid polymerase; (ii) “regular” primer oligonucleotides having sequences comprising hybridizable portions of said known terminal subsequences; and (iii) a “poisoning” oligonucleotide primer, said poisoning primer having a sequence comprising a first subsequence that is a portion of the sequence of one of said known terminal subsequences and a second subsequence that is a hybridizable portion of said putatively unidentified sequence which is adjacent to said one known terminal subsequence, wherein nucleic acids amplified with said poisoning primer are distinguishable upon detection from nucleic acids amplified with said nucleic acids amplified only with said regular primers; separating the products of the contacting step; and the detecting sequence is confirmed if the nucleic acids amplified with said poisoning primer are detected.
摘要翻译： 本发明公开了一种旨在提供肯定确认的方法，核酸具有预测产生观察到的GeneCalling TM信号的推定鉴定序列实际上存在于最初得到信号的样本内。 样品中推测鉴定的核酸片段具有已知末端子序列的3'-和5'-末端，所述方法包括： 在扩增条件下使所述样品中的所述核酸片段与（i）核酸聚合酶接触; （ii）具有包含所述已知末端子序列的可杂交部分的序列的“规则”引物寡核苷酸; 所述中毒引物具有包含作为所述已知末端子序列之一序列的一部分的第一子序列和作为所述假定未鉴定序列的可杂交部分的第二子序列的序列， 与所述一个已知末端子序列相邻，其中用所述中毒引物扩增的核酸在从用所述常规引物扩增的所述核酸扩增的核酸检测时是可区分的; 分离接触步骤的产物; 如果检测到用所述中毒引物扩增的核酸，则确认检测序列。
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10.发明授权Detection and confirmation of nucleic acid sequences by use of poisoning oligonucleotides 失效通过使用中毒寡核苷酸检测和确认核酸序列公开(公告)号：US06673577B1
公开(公告)日：2004-01-06
申请号：US09712018
申请日：2000-11-14
IPC分类号： C12P1934
CPC分类号： C12N15/1093 , C12Q1/6813 , C12Q1/6855
摘要： The present invention discloses a methodology which is directed to providing positive confirmation that nucleic acids, possessing putatively identified sequences predicted to generate observed GeneCalling™ signals, are actually present within the sample from which the signal was originally derived. The putatively identified nucleic acid fragment within the sample possesses 3′- and 5′-ends with known terminal subsequences. The method involves contacting nucleic acid fragments in a sample in amplifying conditions with (i) a nucleic acid polymerase; (ii) “regular” primer oligonucleotides having sequences comprising hybridizable portions of known terminal subsequences; and (iii) a “poisoning” oligonucleotide primer. Nucleic acids amplified with a poisoning primer are distinguishable upon detection from nucleic acids amplified with regular primers.
摘要翻译： 本发明公开了一种旨在提供肯定确认的方法，核酸具有预测产生观察到的GeneCalling TM信号的推测鉴定的序列实际上存在于最初得到该信号的样本内。 样品中推测鉴定的核酸片段具有已知末端亚序列的3'-和5'-末端。 该方法包括在扩增条件下使样品中的核酸片段与（i）核酸聚合酶接触; （ii）具有包括已知末端亚序列的可杂交部分的序列的“常规”引物寡核苷酸; 和（iii）“中毒”寡核苷酸引物。 使用中毒引物扩增的核酸在检测到用常规引物扩增的核酸时是可区分的。
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