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1. 发明申请

WO2012092515A2 METHODS, SYSTEMS, AND COMPUTER READABLE MEDIA FOR NUCLEIC ACID SEQUENCING 审中-公开
标题翻译：用于核酸序列的方法，系统和计算机可读介质
公开(公告)号：WO2012092515A2
公开(公告)日：2012-07-05
申请号：PCT/US2011/067959
申请日：2011-12-29
申请人： LIFE TECHNOLOGIES CORPORATION , DAVEY, Melville , CAWLEY, Simon , WILLIAMS, Alan
发明人： DAVEY, Melville , CAWLEY, Simon , WILLIAMS, Alan
IPC分类号： G06F19/20
CPC分类号： G01N27/4145 , G01N27/27 , G06F19/22
摘要： A method for nucleic acid sequencing includes receiving a plurality of signals indicative of a parameter measured for a plurality of defined spaces, at least some of the defined spaces including one or more sample nucleic acids, the signals being responsive to a plurality of nucleotide flows introducing nucleotides to the defined spaces; determining, for at least some of the defined spaces, whether the defined space includes a sample nucleic acid; processing, for at least some of the defined spaces determined to include a sample nucleic acid, the received signals to improve a quality of the received signals; and predicting a plurality of nucleotide sequences corresponding to respective sample nucleic acids for the defined spaces based on the processed signals and the nucleotide flows.
摘要翻译：一种用于核酸测序的方法包括接收指示针对多个限定空间测量的参数的多个信号，至少一些限定的空间，包括一个或多个样品核酸，所述信号响应多个核苷酸流引入核苷酸到定义的空间; 对于至少一些所定义的空间，确定所定义的空间是否包含样品核酸; 对于被确定为包括样本核酸的至少一些所定义的空间，处理所接收的信号以改善接收信号的质量; 并且基于处理的信号和核苷酸流量预测与定义的空间的各个样品核酸相对应的多个核苷酸序列。

2. 发明申请

WO2013096897A1 METHOD AND APPARATUS FOR CALIBRATION OF A SENSOR ARRAY 审中-公开
标题翻译：传感器阵列校准的方法和装置
公开(公告)号：WO2013096897A1
公开(公告)日：2013-06-27
申请号：PCT/US2012/071471
申请日：2012-12-21
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： REARICK, Todd , DAVEY, Melville , BEAUCHEMIN, Mark
IPC分类号： G01N27/414
CPC分类号： G01N27/4165 , G01N27/4145 , G06F19/22
摘要： A method, computer program product, and system are provided to calibrate a sensor array with a plurality of sensors. Preferably, the sensor array consists of a plurality of ISFETs which are in fluid communication with a reference electrode. A particular reference voltage is determined, which depends on the maximum value of the overall average gain of the sensors in an array, but also on a maximum number of sensors available for the measurement. The method includes sweeping a voltage of the reference electrode from a first voltage to a second voltage. The output voltage of each of the plurality of sensors is monitored at one or more voltages within the first and second voltages. The gain of each sensor at each of the one or more voltages is determined. An overall average gain of the plurality of sensors is calculated at each of the one or more voltages. Further, an acquisition window for the sensor array is determined. The acquisition window includes a maximum distribution of sensors that provides a maximal overall average gain at a particular reference electrode voltage.
摘要翻译：提供了一种方法，计算机程序产品和系统来校准具有多个传感器的传感器阵列。优选地，传感器阵列由与参考电极流体连通的多个ISFET组成。确定特定参考电压，其取决于阵列中传感器的总体平均增益的最大值，也取决于可用于测量的最大传感器数量。该方法包括将参考电极的电压从第一电压扫到第二电压。在第一和第二电压内的一个或多个电压下监视多个传感器中的每一个的输出电压。确定在一个或多个电压中的每一个处的每个传感器的增益。在一个或多个电压中的每一个处计算多个传感器的总平均增益。此外，确定传感器阵列的采集窗口。采集窗口包括在特定参考电极电压下提供最大总平均增益的传感器的最大分布。

3. 发明申请

WO2013025998A1 METHODS, SYSTEMS, AND COMPUTER READABLE MEDIA FOR MAKING BASE CALLS IN NUCLEIC ACID SEQUENCING 审中-公开
标题翻译：方法，系统和计算机可读介质，用于在核酸序列中进行基准测量
公开(公告)号：WO2013025998A1
公开(公告)日：2013-02-21
申请号：PCT/US2012/051361
申请日：2012-08-17
申请人： LIFE TECHNOLOGIES CORPORATION , SIKORA, Marcin , DAVEY, Melville , KOLLER, Christian , CAWLEY, Simon , WILLIAMS, Alan , KULP, David
发明人： SIKORA, Marcin , DAVEY, Melville , KOLLER, Christian , CAWLEY, Simon , WILLIAMS, Alan , KULP, David
IPC分类号： G01N33/48 , G06F19/10
CPC分类号： G06F19/22 , C12Q1/6869 , C12Q2535/122 , C12Q2565/607
摘要： A method for nucleic acid sequencing includes receiving a plurality of observed or measured signals indicative of a parameter observed or measured for a plurality of defined spaces; determining, for at least some of the defined spaces, whether the defined space comprises one or more sample nucleic acids; processing, for at least some of the defined spaces, the observed or measured signal to improve a quality of the observed or measured signal; generating, for at least some of the defined spaces, a set of candidate sequences of bases for the defined space using one or more metrics adapted to associate a score or penalty to the candidate sequences of bases; and selecting the candidate sequence leading to a highest score or a lowest penalty as corresponding to the correct sequence for the one or more sample nucleic acids in the defined space.
摘要翻译：一种用于核酸测序的方法包括：接收多个观察或测量的指示针对多个限定空间观察或测量的参数的信号; 对于至少一些所定义的空间，确定所定义的空间是否包含一个或多个样品核酸; 对于至少一些所定义的空间，处理观察或测量的信号以改善所观察或测量的信号的质量; 为所述定义的空间中的至少一些为所述定义的空间生成一组用于使用一个或多个适于将所述候选序列的分数或惩罚相关联的度量的候选序列的序列集合; 以及选择与所述定义空间中的一个或多个样品核酸的正确序列相对应的最高分数或最低分数的候选序列。

4. 发明申请

WO2012058459A2 PREDICTIVE MODEL FOR USE IN SEQUENCING-BY-SYNTHESIS 审中-公开
标题翻译：用于顺序合成的预测模型
公开(公告)号：WO2012058459A2
公开(公告)日：2012-05-03
申请号：PCT/US2011/058134
申请日：2011-10-27
申请人： LIFE TECHNOLOGIES CORPORATION , DAVEY, Melville , MEYER, Michael
发明人： DAVEY, Melville , MEYER, Michael
IPC分类号： G06G7/58 , G06F19/20 , G06F7/60
CPC分类号： G06F19/12 , C12Q1/6874 , C12Q2537/165
摘要： A method of obtaining a more accurate estimate of a signal correction parameter(s) in sequencing-by-synthesis operations, such as incomplete extension rates, carry forward rates, and/or signal droop rates. The sequencing operation produces signal data. A model is constructed to simulate a population of template strands as it undergoes the sequencing process and becomes divided into different phase-states as the sequencing-by-synthesis progresses. For example, the model may be a phase-state model. The output from the model is used to adjust the signal correction parameter(s). For example, the model may be fitted to the signal data. This fitting results in a more accurate estimate of the signal correction parameter(s). In another embodiment, the signal droop rate is modeled as a decaying function and this decaying function is fitted to the signal data to obtain an improved estimate of the signal droop rate.
摘要翻译：一种在逐个合成操作中获得信号校正参数的更精确估计的方法，例如不完全扩展速率，结转率和/或信号下降率。排序操作产生信号数据。构建模型以模拟模板链的群体，因为其经历了测序过程，并且随着逐个序列合成的进行而分为不同的相态。例如，模型可以是阶段状态模型。模型的输出用于调整信号校正参数。例如，该模型可以适合于信号数据。该拟合导致信号校正参数的更精确的估计。在另一个实施例中，信号下降率被建模为衰减函数，并且该衰减函数适合于信号数据以获得信号下降率的改进估计。

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