公开(公告)号：US20240035094A1

公开(公告)日：2024-02-01

申请号：US18366912

申请日：2023-08-08

Applicant: Life Technologies Corporation

Inventor： Charles SCAFE ,  Dumitru BRINZA ,  James VEITCH ,  Rongsu QI ,  Fiona HYLAND

IPC: C12Q1/6886 ,  G16B30/00 ,  G16B40/00 ,  G16B20/10 ,  C12Q1/6851 ,  C12Q1/6869

CPC classification number: C12Q1/6886 ,  G16B30/00 ,  G16B40/00 ,  G16B20/10 ,  C12Q1/6851 ,  C12Q1/6869 ,  G16B30/20

Abstract: A method for detecting large rearrangements in BRCA1 and BRCA2 genes includes amplifying a nucleic acid sample in the presence of a primer pool to produce amplicons, where the primer pool includes target specific primers targeting regions of exons of the BRCA1 and BRCA2 genes. The method further includes sequencing the amplicons to generate a plurality of reads, mapping the reads to a reference sequence, determining a number of reads per amplicon for the amplicons associated with the exons of the BRCA and the BRCA2 genes, determining exon copy numbers for the exons of the BRCA1 and BRCA2 genes based on the number of reads per amplicon, detecting an exon deletion or duplication based on the exon copy numbers, and detecting a whole gene deletion of the BRCA1 or BRCA2 gene based on the number of reads per amplicon associated with the exons of the BRCA1 and BRCA2 genes.

公开(公告)号：US20210363596A1

公开(公告)日：2021-11-25

申请号：US17389009

申请日：2021-07-29

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Kelli BRAMLETT ,  Dumitru BRINZA ,  Richard CHIEN ,  Dalia DHINGRA ,  Jian GU ,  Ann MONGAN

IPC: C12Q1/6886 ,  C12Q1/6827 ,  C12Q1/6874

Abstract: In some embodiments, the disclosure relates generally to methods, as well as related systems, compositions, kits, apparatuses and computer-readable media, comprising a multiplex molecular tagging procedure that employs a plurality of tags that are appended to a plurality of polynucleotides. The tags have characteristics, including a sequence, length and/or detectable moiety, or any other characteristic, that uniquely identifies the polynucleotide molecule to which it is appended, and permits tracking individual tagged molecules in a mixture of tagged molecules. For example, the tag having a unique tag sequence, can uniquely identify an individual polynucleotide to which it is appended, and distinguish the individual polynucleotide from other tagged polynucleotides in a mixture. In some embodiments, the multiplex molecular tagging procedure can be used for generating error-corrected sequencing data and for detecting a target polynucleotide which is present at low abundance in a nucleic acid sample.

公开(公告)号：US20200027527A1

公开(公告)日：2020-01-23

申请号：US16530015

申请日：2019-08-02

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Fiona Hyland ,  Eric TSUNG ,  Vasisht TADIGOTLA ,  Zheng ZHANG ,  Dumitru BRINZA ,  Onur SAKARYA ,  Xing XU

IPC: G16B30/00

Abstract: Systems and method for determining variants can receive mapped reads, and call variants. In embodiments, flow space information for the reads can be aligned to a flow space representation of a corresponding portion of the reference. Reads spanning a position with a potential variant can be grouped and a score can be calculated for the variant. Based on the scores, a list of probable variants can be provided. In various embodiments, low frequency variants can be identified where multiple potential variants are present at a position.

公开(公告)号：US20240021272A1

公开(公告)日：2024-01-18

申请号：US18330737

申请日：2023-06-07

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Fiona HYLAND ,  Eric TSUNG ,  Vasisht TADIGOTLA ,  Zheng ZHANG ,  Dumitru BRINZA ,  Onur SAKARYA ,  Xing XU

IPC: G16B30/10 ,  G16B30/00

CPC classification number: G16B30/10 ,  G16B30/00

Abstract: Systems and method for determining variants can receive mapped reads, and call variants. In embodiments, flow space information for the reads can be aligned to a flow space representation of a corresponding portion of the reference. Reads spanning a position with a potential variant can be grouped and a score can be calculated for the variant. Based on the scores, a list of probable variants can be provided. In various embodiments, low frequency variants can be identified where multiple potential variants are present at a position.

公开(公告)号：US20200051663A1

公开(公告)日：2020-02-13

申请号：US16279315

申请日：2019-02-19

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Zheng ZHANG ,  Danwei GUO ,  Yuandan LOU ,  Asim SIDDIQUI ,  Dumitru BRINZA

IPC: G16B30/00

Abstract: Nucleic acid sequence mapping/assembly methods are disclosed. The methods initially map only a contiguous portion of each read to a reference sequence and then extends the mapping of the read at both ends of the mapped contiguous portion until the entire read is mapped (aligned). In various embodiments, a mapping score can be calculated for the read alignment using a scoring function, score (i, j)=M+mx, where M can be the number of matches in the extended alignment, x can be the number of mismatches in the alignment, and m can be a negative penalty for each mismatch. The mapping score can be utilized to rank or choose the best alignment for each read.

公开(公告)号：US20190323091A1

公开(公告)日：2019-10-24

申请号：US16503262

申请日：2019-07-03

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Kelli BRAMLETT ,  Dumitru BRINZA ,  Richard CHIEN ,  Dalia DHINGRA ,  Jian GU ,  Ann MONGAN

IPC: C12Q1/6886 ,  C12Q1/6827 ,  C12Q1/6874

Abstract: In some embodiments, the disclosure relates generally to methods, as well as related systems, compositions, kits, apparatuses and computer-readable media, comprising a multiplex molecular tagging procedure that employs a plurality of tags that are appended to a plurality of polynucleotides. The tags have characteristics, including a sequence, length and/or detectable moiety, or any other characteristic, that uniquely identifies the polynucleotide molecule to which it is appended, and permits tracking individual tagged molecules in a mixture of tagged molecules. For example, the tag having a unique tag sequence, can uniquely identify an individual polynucleotide to which it is appended, and distinguish the individual polynucleotide from other tagged polynucleotides in a mixture. In some embodiments, the multiplex molecular tagging procedure can be used for generating error-corrected sequencing data and for detecting a target polynucleotide which is present at low abundance in a nucleic acid sample.

公开(公告)号：US20190087539A1

公开(公告)日：2019-03-21

申请号：US16136463

申请日：2018-09-20

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Rajesh GOTTIMUKKALA ,  Cheng-Zong BAI ,  Dumitru BRINZA ,  Jeoffrey SCHAGEMAN ,  Varun BAGAI

IPC: G06F19/22 ,  C12Q1/6853

Abstract: A method for compressing nucleic acid sequence data wherein each sequence read is associated with a molecular tag sequence, wherein a portion of the sequence reads alignments correspond to sequence reads mapped to a targeted fusion reference sequence includes determining a consensus sequence read for each family of sequence reads based on flow space signal measurements corresponding to the family of sequence reads, determining a consensus sequence alignment for each family of sequence reads, wherein a portion of the consensus sequence alignments correspond to the consensus sequence reads aligned with the targeted fusion reference sequence, generating a compressed data structure comprising consensus compressed data, the consensus compressed data including the consensus sequence read and the consensus sequence alignment for each family, and detecting a fusion using the consensus sequence reads and the consensus sequence alignments from the compressed data structure.

公开(公告)号：US20140052381A1

公开(公告)日：2014-02-20

申请号：US13966378

申请日：2013-08-14

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Sowmi UTIRAMERUR ,  Dumitru BRINZA ,  Marcin SIKORA ,  Christian KOLLER ,  Earl HUBBELL ,  Chantal ROTH ,  Rajesh GOTTIMUKKALA

IPC: G06F19/22

CPC classification number: 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.

Abstract translation: 用于确定变体的系统和方法可以接收映射读取并且从均聚物区域的多次读取确定匹配滤波器残差分布的分布。 匹配滤波器残差的分布可以适用于单模和双模态模型。 基于最适合匹配滤波器残差分布的模型，可以确定样品的杂合度和均聚物中插入/缺失的不存在或不存在。

公开(公告)号：US20210108264A1

公开(公告)日：2021-04-15

申请号：US16948915

申请日：2020-10-06

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Dumitru BRINZA ,  Zheng ZHANG ,  Fiona HYLAND ,  Rajesh GOTTIMUKKALA

IPC: C12Q1/6874 ,  G16B30/00

Abstract: Systems and method for determining variants can receive mapped reads, align flow space information to a flow space representation of a corresponding portion of the reference. Reads spanning a position with a potential variant can be evaluated in a context specific manner. A list of probable variants can be provided.

公开(公告)号：US20160362748A1

公开(公告)日：2016-12-15

申请号：US15178450

申请日：2016-06-09

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Ann MONGAN ,  Richard CHIEN ,  Dumitru BRINZA ,  Kelli BRAMLETT

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q2600/156 ,  C12Q2525/191 ,  C12Q2531/113 ,  C12Q2535/122 ,  C12Q2537/143 ,  C12Q2565/514

Abstract: In some embodiments, the disclosure relates generally to methods, as well as related systems, compositions, kits, apparatuses and computer-readable media, comprising a multiplex molecular tagging procedure that employs a plurality of tags that are appended to a plurality of polynucleotides. The tags have characteristics, including a sequence, length and/or detectable moiety, or any other characteristic, that uniquely identifies the polynucleotide molecule to which it is appended, and permits tracking individual tagged molecules in a mixture of tagged molecules. For example, the tag having a unique tag sequence, can uniquely identify an individual polynucleotide to which it is appended, and distinguish the individual polynucleotide from other tagged polynucleotides in a mixture. In some embodiments, the multiplex molecular tagging procedure can be used for generating error-corrected sequencing data and for detecting a target polynucleotide which is present at low abundance in a nucleic acid sample.

Abstract translation: 在一些实施方案中，本公开一般涉及方法以及相关系统，组合物，试剂盒，装置和计算机可读介质，其包含使用附加到多个多核苷酸的多个标签的多重分子标记过程。 标签具有特征，包括序列，长度和/或可检测部分，或唯一地识别其附着的多核苷酸分子的任何其它特征，并允许跟踪标记分子混合物中的单个标记分子。 例如，具有唯一标签序列的标签可以唯一地识别其所附着的单个多核苷酸，并将单个多核苷酸与混合物中的其他标记多核苷酸区分开。 在一些实施方案中，多重分子标记方法可用于产生错误校正的测序数据和用于检测以核酸样品中低丰度存在的靶多核苷酸。