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    ANALYSIS OF A POLYNUCLEOTIDE VIA A NANOPORE SYSTEM
    1.
    发明申请
    ANALYSIS OF A POLYNUCLEOTIDE VIA A NANOPORE SYSTEM 审中-公开
    通过纳米系统分析多核苷酸

    公开(公告)号：US20150344944A1

    公开(公告)日：2015-12-03

    申请号：US14653656

    申请日：2013-12-19

    申请人： OXFORD NANOPORE TECHNOLOGIES LIMITED

    发明人： Stuart William Reid ,  Gavin Harper

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6869 ,  C12Q1/6806 ,  C12Q2525/161 ,  C12Q2525/197 ,  C12Q2565/631

    摘要： A target polynucleotide is expanded. In respect of each nucleotide in the target polynucleotide, the target polynucleotide comprises clock nucleotides and at least one signal nucleotide in a predetermined order. The clock nucleotides have a predetermined sequence common to each nucleotide in the target polynucleotide. The at least one signal nucleotide is characteristic of the identity of the respective nucleotide in the target polynucleotide. During translocation of the expanded polynucleotide through a nanopore, electrical measurements dependent on the polynucleotide within the pore are made, to derive an analysis signal. Clock signals derived from the clock nucleotides are identified. Relative to the positions of the identified clock signals, nucleotide signals derived from the least one signal nucleotide are derived to analyse the target polynucleotide. The predetermined sequence of the clock nucleotides comprises a restriction site for a restriction enzyme and at least one further nucleotide that extends the predetermined sequence.

    摘要翻译： 靶多核苷酸被扩增。 关于靶多核苷酸中的每个核苷酸，靶多核苷酸以预定顺序包括时钟核苷酸和至少一个信号核苷酸。 时钟核苷酸具有靶多核苷酸中每个核苷酸共有的预定序列。 至少一个信号核苷酸是目标多核苷酸中相应核苷酸的特征。 在扩增的多核苷酸在通过纳米孔的移位期间，进行取决于孔内的多核苷酸的电测量，以得到分析信号。 识别从时钟核苷酸得到的时钟信号。 相对于识别的时钟信号的位置，衍生自至少一个信号核苷酸的核苷酸信号被导出以分析靶多核苷酸。 时钟核苷酸的预定序列包​​含限制酶的限制性位点和延伸预定序列的至少一个其它核苷酸。

    Analysis of a polynucleotide via a nanopore system
    2.
    发明授权
    Analysis of a polynucleotide via a nanopore system 有权

    公开(公告)号：US11085077B2

    公开(公告)日：2021-08-10

    申请号：US16162848

    申请日：2018-10-17

    申请人： Oxford Nanopore Technologies Limited

    发明人： Stuart William Reid ,  Gavin Harper

    IPC分类号： C12Q1/68 ,  C12Q1/6869 ,  C12Q1/6806

    摘要： A target polynucleotide is expanded. In respect of each nucleotide in the target polynucleotide, the target polynucleotide comprises clock nucleotides and at least one signal nucleotide in a predetermined order. The clock nucleotides have a predetermined sequence common to each nucleotide in the target polynucleotide. The at least one signal nucleotide is characteristic of the identity of the respective nucleotide in the target polynucleotide. During translocation of the expanded polynucleotide through a nanopore, electrical measurements dependent on the polynucleotide within the pore are made, to derive an analysis signal. Clock signals derived from the clock nucleotides are identified. Relative to the positions of the identified clock signals, nucleotide signals derived from the least one signal nucleotide are derived to analyse the target polynucleotide. The predetermined sequence of the clock nucleotides comprises a restriction site for a restriction enzyme and at least one further nucleotide that extends the predetermined sequence.

    METHOD FOR DETERMINING A POLYMER SEQUENCE
    4.
    发明申请
    METHOD FOR DETERMINING A POLYMER SEQUENCE 有权

    公开(公告)号：US20220213541A1

    公开(公告)日：2022-07-07

    申请号：US17272986

    申请日：2019-09-04

    申请人： Oxford Nanopore Technologies Limited

    发明人： Clive Gavin Brown ,  Timothy Lee Massingham ,  Stuart William Reid

    IPC分类号： C12Q1/6869 ,  G16B40/10 ,  G16B40/20

    摘要： The invention resides in a method of determining a sequence of a target polymer, or part thereof, comprising polymer units comprising canonical and non-canonical polymer units. The method comprises taking a series of measurements of a signal relating to the target polymer wherein a measurement of the signal is dependent upon a plurality of polymer units, and wherein the polymer units of the target polymer modulate the signal, and wherein a non-canonical polymer unit modulates the signal differently from a corresponding canonical polymer unit. The series of measurements are analysed using a machine learning technique that attributes a measurement of a non-canonical polymer unit to being a measurement of a respective corresponding canonical polymer unit. The sequence of the target polymer, or part thereof, is determined from the analysed series of measurements. A non-canonical polymer unit identified from the analysis can be additionally or alternatively determined. Two or more types of non-canonical polymer units corresponding to the two or more types of canonical polymer unit can be used. The polynucleotide can be DNA.

    ANALYSIS OF A POLYNUCLEOTIDE VIA A NANOPORE SYSTEM
    6.
    发明申请
    ANALYSIS OF A POLYNUCLEOTIDE VIA A NANOPORE SYSTEM 审中-公开

    公开(公告)号：US20190203286A1

    公开(公告)日：2019-07-04

    申请号：US16162848

    申请日：2018-10-17

    申请人： Oxford Nanopore Technologies Limited

    发明人： Stuart William Reid ,  Gavin Harper

    IPC分类号： C12Q1/6869 ,  C12Q1/6806

    CPC分类号： C12Q1/6869 ,  C12Q1/6806 ,  C12Q2525/161 ,  C12Q2525/197 ,  C12Q2565/631

    摘要： A target polynucleotide is expanded. In respect of each nucleotide in the target polynucleotide, the target polynucleotide comprises clock nucleotides and at least one signal nucleotide in a predetermined order. The clock nucleotides have a predetermined sequence common to each nucleotide in the target polynucleotide. The at least one signal nucleotide is characteristic of the identity of the respective nucleotide in the target polynucleotide. During translocation of the expanded polynucleotide through a nanopore, electrical measurements dependent on the polynucleotide within the pore are made, to derive an analysis signal. Clock signals derived from the clock nucleotides are identified. Relative to the positions of the identified clock signals, nucleotide signals derived from the least one signal nucleotide are derived to analyse the target polynucleotide. The predetermined sequence of the clock nucleotides comprises a restriction site for a restriction enzyme and at least one further nucleotide that extends the predetermined sequence.

    ANALYSIS OF A POLYMER COMPRISING POLYMER UNITS
    7.
    发明申请
    ANALYSIS OF A POLYMER COMPRISING POLYMER UNITS 审中-公开
    包含聚合物单体的聚合物分析

    公开(公告)号：US20160162634A1

    公开(公告)日：2016-06-09

    申请号：US14346549

    申请日：2012-09-21

    申请人： OXFORD NANOPORE TECHNOLOGIES LIMITED

    发明人： Stuart William Reid ,  Gavin Harper ,  Clive Gavin Brown ,  James Anthony Clarke ,  Andrew John Heron

    IPC分类号： G06F19/22 ,  G01N33/483 ,  G06F17/18

    CPC分类号： G01N33/48721 ,  B82Y15/00 ,  C12Q1/6869 ,  G01N27/44791 ,  G01N33/483 ,  G06F17/18 ,  G06N7/005 ,  G16B30/00 ,  C12Q2537/165 ,  C12Q2565/631

    摘要： A sequence of polymer units in a polymer (3), eg. DNA, is estimated from at least one series of measurements related to the polymer, eg. ion current as a function of translocation through a nanopore (1), wherein the value of each measurement is dependent on a k-mer being a group of k polymer units (4). A probabilistic model, especially a hidden Markov model (HMM), is provided, comprising, for a set of possible k-mers: transition weightings representing the chances of transitions from origin k-mers to destination k-mers; and emission weightings in respect of each k-mer that represent the chances of observing given values of measurements for that k-mer. The series of measurements is analysed using an analytical technique, eg. Viterbi decoding, that refers to the model and estimates at least one estimated sequence of polymer units in the polymer based on the likelihood predicted by the model of the series of measurements being produced by sequences of polymer units. In a further embodiment, different voltages are applied across the nanopore during translocation in order to improve the resolution of polymer units.

    摘要翻译： 聚合物（3）中的聚合物单元序列，例如 DNA，从与聚合物相关的至少一系列测量估计，例如。 作为通过纳米孔（1）的易位的函数的离子电流，其中每个测量的值取决于作为k个聚合物单元（4）的组的k-mer。 提供概率模型，特别是隐马尔可夫模型（HMM），包括一组可能的k-mers：转换权重，表示从原始k-mers到目的地k-mers的转换机会; 和每个k-mer的发射权重，其表示观察该k-mer的给定值的测量值的机会。 使用分析技术分析一系列测量结果，例如。 维特比解码，其是指模型并且基于通过由聚合物单元的序列产生的一系列测量的模型预测的可能性估计聚合物中的聚合物单元的至少一个估计序列。 在另一个实施方案中，在易位期间跨纳米孔施加不同的电压，以改善聚合物单元的分辨率。