公开(公告)号：US12146189B2

公开(公告)日：2024-11-19

申请号：US16433380

申请日：2019-06-06

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Earl Hubbell

IPC: C40B50/16 ,  C12Q1/6869 ,  C12Q1/6874 ,  C40B20/04 ,  C40B70/00 ,  G16B30/00 ,  G16C20/64 ,  G16C99/00

Abstract: A method for sequencing a polynucleotide sample having a barcode sequence includes: introducing a series of nucleotides to the polynucleotide sample according to a predetermined order of nucleotide flows; obtaining a series of signals resulting from the introducing of nucleotides to the polynucleotide sample; and resolving the series of signals over the barcode sequence to render a flowspace string, wherein the flowspace string is a codeword of an error-correcting code that is (i) designed based on and adapted for use with the predetermined order of nucleotide flows, and (ii) capable of distinguishing any codeword in the error-correcting code from the other codewords in the error-correcting code in the presence of zero, one, and two errors.

公开(公告)号：US11636919B2

公开(公告)日：2023-04-25

申请号：US15974976

申请日：2018-05-09

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Earl Hubbell ,  Sowmi Utiramerur

IPC: G16B20/20 ,  G16B30/00 ,  G16B40/00 ,  C12Q1/6874 ,  C12Q1/6869

Abstract: A method for evaluating variant likelihood includes: providing a plurality of template polynucleotide strands, sequencing primers, and polymerase in a plurality of defined spaces disposed on a sensor array; exposing the plurality of template polynucleotide strands, sequencing primers, and polymerase to a series of flows of nucleotide species according to a predetermined order; obtaining measured values corresponding to an ensemble of sequencing reads for at least some of the template polynucleotide strands in at least one of the defined spaces; and evaluating a likelihood that a variant sequence is present given the measured values corresponding to the ensemble of sequencing reads, the evaluating comprising: determining a measurement confidence value for each read in the ensemble of sequencing reads and modifying at least some model-predicted values using a first bias for forward strands and a second bias for reverse strands.

公开(公告)号：US20140296080A1

公开(公告)日：2014-10-02

申请号：US14200942

申请日：2014-03-07

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Earl Hubbell ,  Sowmi Utiramerur

IPC: G06F19/22 ,  C12Q1/68

CPC classification number: G16B30/00 ,  C12Q1/6874 ,  G16B40/00

Abstract: A method for evaluating variant likelihood includes: providing a plurality of template polynucleotide strands, sequencing primers, and polymerase in a plurality of defined spaces disposed on a sensor array; exposing the plurality of template polynucleotide strands, sequencing primers, and polymerase to a series of flows of nucleotide species according to a predetermined order; obtaining measured values corresponding to an ensemble of sequencing reads for at least some of the template polynucleotide strands in at least one of the defined spaces; and evaluating a likelihood that a variant sequence is present given the measured values corresponding to the ensemble of sequencing reads, the evaluating comprising: determining a measurement confidence value for each read in the ensemble of sequencing reads and modifying at least some model-predicted values using a first bias for forward strands and a second bias for reverse strands.

Abstract translation: 用于评估变异可能性的方法包括：在设置在传感器阵列上的多个限定空间中提供多个模板多核苷酸链，测序引物和聚合酶; 根据预定顺序将多个模板多核苷酸链，测序引物和聚合酶暴露于一系列核苷酸种类的流中; 获得对应于至少一个所述定义的空间中的至少一些模板多核苷酸链的测序读集合的测量值; 并且评估变量序列存在的可能性，给定对应于测序集合的测量值，所述评估包括：确定测序集合中每次读取的测量置信度值，并且使用以下步骤修改至少一些模型预测值 正向链的第一偏倚和反向链的第二偏倚。

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.

公开(公告)号：US20200032334A1

公开(公告)日：2020-01-30

申请号：US16433380

申请日：2019-06-06

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Earl Hubbell

IPC: C12Q1/6874 ,  C40B50/16 ,  C40B20/04 ,  C40B70/00 ,  C12Q1/6869 ,  G16C99/00

Abstract: A method for sequencing a polynucleotide sample having a barcode sequence includes: introducing a series of nucleotides to the polynucleotide sample according to a predetermined order of nucleotide flows; obtaining a series of signals resulting from the introducing of nucleotides to the polynucleotide sample; and resolving the series of signals over the barcode sequence to render a flowspace string, wherein the flowspace string is a codeword of an error-correcting code that is (i) designed based on and adapted for use with the predetermined order of nucleotide flows, and (ii) capable of distinguishing any codeword in the error-correcting code from the other codewords in the error-correcting code in the presence of zero, one, and two errors.

公开(公告)号：US10370708B2

公开(公告)日：2019-08-06

申请号：US15236172

申请日：2016-08-12

Applicant: Life Technologies Corporation

Inventor： Earl Hubbell ,  Jonathan Schultz

IPC: C12Q1/68 ,  C12Q1/6869 ,  C12Q1/6874

Abstract: A system and machine readable medium for nucleic acid sequencing includes disposing template polynucleotide strands in 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; exposing the template polynucleotide strands to a series of flows of nucleotide species flowed according to a predetermined ordering; and determining, for each of the series of flows of nucleotide species, how many nucleotide incorporations occurred for that particular flow to determine a predicted sequence of nucleotides corresponding to the template polynucleotide strands, wherein the predetermined ordering (a) is not a series of consecutive repetitions of a 4-flow permutation of four different nucleotide species, (b) is not specifically tailored to a particular combination of a particular template polynucleotide strand to be sequenced and a particular sequencing primer to be used, and (c) comprises a phase-protecting flow ordering.

公开(公告)号：US09515676B2

公开(公告)日：2016-12-06

申请号：US13754566

申请日：2013-01-30

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Charles Sugnet ,  Simon Cawley ,  Mohit Gupta ,  Iztok Marjanovic ,  Todd Rearick ,  Mark Beauchemin ,  Earl Hubbell

IPC: G06F19/24 ,  G11C17/00 ,  H03M7/30

CPC classification number: H03M7/30 ,  G06F19/24

Abstract: A compression method includes measuring a waveform associated with a chemical event occurring on a sensor array, wherein the waveform comprises at least one region associated with expected measured values and at least one region associated with unpredictable measured values; applying a first compression process to the waveform, the first compression process including an averaging of one or more frames in one or more portions of the waveform; and applying a second compression process to the waveform, the second compression process including a truncating of data corresponding to a portion of the waveform that is not related to a nucleotide incorporation component of the waveform.

Abstract translation: 压缩方法包括测量与传感器阵列上发生的化学事件相关联的波形，其中所述波形包括与预期测量值相关联的至少一个区域和与不可预测的测量值相关联的至少一个区域; 对所述波形应用第一压缩处理，所述第一压缩处理包括所述波形的一个或多个部分中的一个或多个帧的平均值; 以及对所述波形应用第二压缩处理，所述第二压缩处理包括对应于与所述波形的核苷酸掺入成分无关的所述波形的一部分的数据的截断。

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

IPC: G16B30/10 ,  G16B20/20 ,  G16B30/00

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.

公开(公告)号：US10597711B2

公开(公告)日：2020-03-24

申请号：US13859360

申请日：2013-04-09

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Earl Hubbell ,  Jonathan Schultz

IPC: C12Q1/68 ,  C12Q1/6869 ,  C12Q1/6874

Abstract: A method for nucleic acid sequencing includes: disposing a plurality of template polynucleotide strands, sequencing primers, and polymerases in a plurality of defined spaces of a sensor array; exposing template polynucleotide strands to a series of flows of nucleotide species, the series comprising a sequence of random flows; and obtaining, for each of the series of flows of nucleotide species, a signal indicative of how many nucleotide incorporations occurred for that particular flow to determine a predicted sequence of nucleotides corresponding to the template polynucleotide strands.

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.