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1.
公开(公告)号:US11474070B2
公开(公告)日:2022-10-18
申请号:US16196502
申请日:2018-11-20
Applicant: LIFE TECHNOLOGIES CORPORATION
Inventor: Marcin Sikora , Melville Davey , Christian Koller , Simon Cawley , Alan Williams , David Kulp
IPC: G01N27/414 , G16B30/00 , G16B30/10 , C12Q1/6869 , G01N27/27 , G16B30/20
Abstract: 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.
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公开(公告)号:US20250061970A1
公开(公告)日:2025-02-20
申请号:US18816167
申请日:2024-08-27
Applicant: Life Technologies Corporation
Inventor: Sowmi Utiramerur , Dumitru Brinza , Marcin Sikora , Christian Koller , Earl Hubbell , Chantal Roth , Rajesh Gottimukkala
Abstract: Systems and method for determining variants can receive mapped reads and determine a distribution of matched-filter residuals distribution from a plurality of reads at a homopolymer region. The distribution of matched-filter residuals can be fit to uni-modal and bi-modal models. Based on the model that best fits the distribution of matched-filter residuals, the heterozygosity of the sample and the absence or presence of an insertion/deletion in the homopolymer can be determined.
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公开(公告)号:US20200024656A1
公开(公告)日:2020-01-23
申请号:US16429266
申请日:2019-06-03
Applicant: LIFE TECHNOLOGIES CORPORATION
Inventor: Earl Hubbell , Christian Koller , Nils Homer
IPC: C12Q1/6869
Abstract: A method for sequencing a nucleic acid template includes: (a) performing a first sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a first predetermined ordering of nucleotides and/or reagents to obtain a first sequencing result; (b) after the first sequencing process, performing a second sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a second predetermined ordering of nucleotides and/or reagents to obtain a second sequencing result, the second predetermined ordering of nucleotides and/or reagents being different from the first predetermined ordering of nucleotides and/or reagents and at least one of the first and second predetermined orderings of nucleotides and/or reagents being designed for repeat sequencing; and (c) determining a sequence of bases corresponding to at least a portion of the nucleic acid template using both the first sequencing result and the second sequencing result.
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公开(公告)号:US11655500B2
公开(公告)日:2023-05-23
申请号:US16429266
申请日:2019-06-03
Applicant: LIFE TECHNOLOGIES CORPORATION
Inventor: Earl Hubbell , Christian Koller , Nils Homer
IPC: C12Q1/6869 , G16B30/00
CPC classification number: C12Q1/6869 , G16B30/00 , C12Q2535/122 , C12Q1/6869 , C12Q2525/179 , C12Q2535/119 , C12Q2537/165
Abstract: A method for sequencing a nucleic acid template includes: (a) performing a first sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a first predetermined ordering of nucleotides and/or reagents to obtain a first sequencing result; (b) after the first sequencing process, performing a second sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a second predetermined ordering of nucleotides and/or reagents to obtain a second sequencing result, the second predetermined ordering of nucleotides and/or reagents being different from the first predetermined ordering of nucleotides and/or reagents and at least one of the first and second predetermined orderings of nucleotides and/or reagents being designed for repeat sequencing; and (c) determining a sequence of bases corresponding to at least a portion of the nucleic acid template using both the first sequencing result and the second sequencing result.
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5.
公开(公告)号:US20250061969A1
公开(公告)日:2025-02-20
申请号:US18818866
申请日:2024-08-29
Applicant: Life Technologies Corporation
Inventor: Marcin Sikora , Earl Hubbell , Simon Cawley , Christian Koller
IPC: G16B30/00 , G01N27/27 , G01N27/414 , G16B25/00 , G16B30/10
Abstract: A method for nucleic acid sequencing includes: receiving a signal comprising measurements of a parameter measured in response to a plurality of nucleotide flows flowed in a space comprising a sample nucleic acid; normalizing the signal to obtain a normalized signal; adaptively normalizing the normalized signal to obtain an adaptively normalized signal; and predicting a sequence of base calls corresponding to the sample nucleic acid using the adaptively normalized signal.
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6.
公开(公告)号:US11636922B2
公开(公告)日:2023-04-25
申请号:US16550374
申请日:2019-08-26
Applicant: LIFE TECHNOLOGIES CORPORATION
Inventor: Christian Koller , Marcin Sikora , Peter Vander Horn
Abstract: A method for nucleic acid sequencing includes receiving observed or measured nucleic acid sequencing data from a sequencing instrument that receives and processes a sample nucleic acid in a termination sequencing-by-synthesis process. The method also includes generating a set of candidate sequences of bases for the observed or measured nucleic acid sequencing data by determining a predicted signal for candidate sequences using a simulation framework. The simulation framework incorporates an estimated carry forward rate (CFR), an estimated incomplete extension rate (IER), an estimated droop rate (DR), an estimated reactivated molecules rate (RMR), and an estimated termination failure rate (TFR), the RMR being greater than or equal to zero and the TFR being lesser than one. The method also includes identifying, from the set of candidate sequences of bases, one candidate sequence leading to optimization of a solver function as corresponding to the sequence for the sample nucleic acid.
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公开(公告)号:US10978174B2
公开(公告)日:2021-04-13
申请号:US15154499
申请日:2016-05-13
Applicant: LIFE TECHNOLOGIES CORPORATION
Inventor: Christian Koller , Michael D. Allen
IPC: G16B30/00 , C12Q1/6869 , C12Q1/6874
Abstract: Methods, system, and kits are provided for sample identification, and, more specifically, for designing, and/or making, and/or using sample discriminating codes or barcodes for identifying sample nucleic acids or other biomolecules or polymers. For example, a plurality of flowspace codewords may be generated, the codewords comprising a string of characters. A location for at least one padding character within the flowspace codewords may be determined. The padding character may be inserted into the flowspace codewords at the determined location. After the inserting, a plurality of the flowspace codewords may be selected based on satisfying a predetermined minimum distance criteria, wherein the selected codewords correspond to valid base space sequences according to a predetermined flow order. And the barcode sequences corresponding to the selected codewords may be manufactured.
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8.
公开(公告)号:US20190170680A1
公开(公告)日:2019-06-06
申请号:US16196502
申请日:2018-11-20
Applicant: LIFE TECHNOLOGIES CORPORATION
Inventor: Marcin Sikora , Melville Davey , Christian Koller , Simon Cawley , Alan Williams , David Kulp
IPC: G01N27/414 , G16B30/00
Abstract: 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.
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公开(公告)号:US20140274733A1
公开(公告)日:2014-09-18
申请号:US14205492
申请日:2014-03-12
Applicant: LIFE TECHNOLOGIES CORPORATION
Inventor: Christian Koller , Zheng ZHANG
IPC: C12Q1/68
CPC classification number: C12Q1/6874 , G16B30/00
Abstract: A method for nucleic acid sequencing includes: (a) disposing a plurality of template polynucleotide strands in a plurality of defined spaces disposed on a sensor array, at least some of the template polynucleotide strands having a sequencing primer and a polymerase operably bound therewith; (b) exposing the template polynucleotide strands with the sequencing primer and a polymerase operably bound therewith to a series of flows of nucleotide species flowed according to a predetermined ordering; (c) determining sequence information for a plurality of the template polynucleotide strands in the defined spaces based on the flows of nucleotide species to generate a plurality of sequencing reads corresponding to the template polynucleotide strands; and (d) aligning the plurality of sequencing reads using an alignment process comprising a first set of alignment criteria or penalties that are based on biological changes in sequence and a second set of alignment criteria or penalties that are based on a sequencing error mode.
Abstract translation: 用于核酸测序的方法包括:(a)将多个模板多核苷酸链设置在设置在传感器阵列上的多个限定的空间中,至少一些模板多核苷酸链具有测序引物和与之可操作地结合的聚合酶; (b)用测序引物和可操作地与其结合的聚合酶将模板多核苷酸链暴露于根据预定顺序流过的一系列核苷酸物质流; (c)基于核苷酸物种的流量确定多个定义空间中的模板多核苷酸链的序列信息,以产生对应于模板多核苷酸链的多个测序读数; 并且(d)使用包括基于顺序的生物变化的第一组对准标准或惩罚的对准过程对齐多个测序读数,以及基于排序误差模式的第二组比对标准或惩罚。
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公开(公告)号:US12077818B2
公开(公告)日:2024-09-03
申请号:US18297049
申请日:2023-04-07
Applicant: LIFE TECHNOLOGIES CORPORATION
Inventor: Earl Hubbell , Christian Koller , Nils Homer
IPC: C12Q1/6869 , G16B30/00
CPC classification number: C12Q1/6869 , G16B30/00 , C12Q2535/122 , C12Q1/6869 , C12Q2525/179 , C12Q2535/119 , C12Q2537/165
Abstract: A method for sequencing a nucleic acid template includes: (a) performing a first sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a first predetermined ordering of nucleotides and/or reagents to obtain a first sequencing result; (b) after the first sequencing process, performing a second sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a second predetermined ordering of nucleotides and/or reagents to obtain a second sequencing result, the second predetermined ordering of nucleotides and/or reagents being different from the first predetermined ordering of nucleotides and/or reagents and at least one of the first and second predetermined orderings of nucleotides and/or reagents being designed for repeat sequencing; and (c) determining a sequence of bases corresponding to at least a portion of the nucleic acid template using both the first sequencing result and the second sequencing result.
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