公开(公告)号：WO2015123269A1

公开(公告)日：2015-08-20

申请号：PCT/US2015/015375

申请日：2015-02-11

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz

IPC: C12Q1/68 ,  G06F19/22 ,  G06F19/10 ,  G06F17/30

CPC classification number: G06F19/22 ,  C12Q1/6869 ,  C12Q1/6883 ,  C12Q2521/301 ,  G06F19/26 ,  C12Q2537/165

Abstract: The invention provides methods for comparing one set of genetic sequences to another without discarding any information within either set. A set of genetic sequences is represented using a directed acyclic graph (DAG) avoiding any unwarranted reduction to a linear data structure. The invention provides a way to align one sequence DAG to another to produce an alignment that can itself be stored as a DAG. DAG-to-DAG alignment is a natural choice wherever a set of genomic information consisting of more than one string needs to be compared to any non-linear reference. For example, a subpopulation DAG could be compared to a population DAG in order to compare the genetic features of that subpopulation to those of the population.

Abstract translation: 本发明提供了将一组遗传序列与另一组遗传序列进行比较而不丢弃任一组内的任何信息的方法。 使用有向无环图（DAG）表示一组遗传序列，避免了线性数据结构的任何不必要的减少。 本发明提供了将一个序列DAG与另一序列对准的方法，以产生本身可以作为DAG存储的对准。 无论从多个字符串组成的一组基因组信息需要与任何非线性参考进行比较，DAG到DAG对齐是一种自然选择。 例如，可以将亚群DAG与群体DAG进行比较，以便将该亚群体的遗传特征与群体的遗传特征进行比较。

公开(公告)号：WO2015061099A1

公开(公告)日：2015-04-30

申请号：PCT/US2014/060680

申请日：2014-10-15

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz ,  MEYVIS, Nathan

IPC: G06F19/10

CPC classification number: G06F19/22 ,  G06F19/28

Abstract: The invention generally provides systems and methods for analysis of RNA-Seq reads in which an annotated reference is represented as a directed acyclic graph (DAG) or similar data structure. Features such as exons and introns from the reference provide nodes in the DAG and those features are linked as pairs in their canonical genomic order by edges. The DAG can scale to any size and can in fact be populated in the first instance by import from an extrinsic annotated reference.

Abstract translation: 本发明通常提供用于分析RNA-Seq读取的系统和方法，其中注释的引用被表示为有向无环图（DAG）或类似的数据结构。 来自参考文献的功能如外显子和内含子提供DAG中的节点，并且这些特征通过边缘以其规范基因组顺序链接成对。 DAG可以扩展到任何大小，实际上可以通过从外部注释引用导入而在第一个实例中进行填充。

公开(公告)号：WO2015048753A1

公开(公告)日：2015-04-02

申请号：PCT/US2014/058328

申请日：2014-09-30

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz

IPC: G06F19/22 ,  C12Q1/68 ,  C40B40/06 ,  C40B60/12

CPC classification number: G06F19/22 ,  C12Q1/6874 ,  C12Q2535/122 ,  C12Q2537/165

Abstract: The invention provides methods for identifying rare variants near a structural variation in a genetic sequence, for example, in a nucleic acid sample taken from a subject. The invention additionally includes methods for aligning reads (e.g., nucleic acid reads) to a reference sequence construct accounting for the structural variation, methods for building a reference sequence construct accounting for the structural variation or the structural variation and the rare variant, and systems that use the alignment methods to identify rare variants. The method is scalable, and can be used to align millions of reads to a construct thousands of bases long, or longer.

Abstract translation: 本发明提供用于鉴定遗传序列中结构变异附近的罕见变体的方法，例如在取自受试者的核酸样品中。 本发明还包括用于将读取（例如，核酸读取）与构成结构变异的参考序列构型对齐的方法，构建结构变异或结构变异的参考序列构建的方法和稀有变体，以及系统， 使用对齐方法来识别稀有变体。 该方法是可扩展的，并且可以用于将数百万次读取与数千个基准长或更长的时间对齐。

公开(公告)号：WO2015105963A1

公开(公告)日：2015-07-16

申请号：PCT/US2015/010604

申请日：2015-01-08

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz

IPC: C12Q1/68

CPC classification number: G06F19/22 ,  G06F19/00

Abstract: The invention generally relates to genomic studies and specifically to improved methods for read mapping using identified nucleotides at known locations. The invention provides methods of using identified nucleotides at known places in a genome to guide the analysis of sequence reads from that genome by excluding potential mappings or assemblies that are not congruent with the identified nucleotides. Information about a plurality of SNPs in the subject's genome is used to identify candidate paths through a genomic directed acyclic graph (DAG). Sequence reads are mapped to the candidate paths.

Abstract translation: 本发明一般涉及基因组研究，特别涉及使用已知位置处的鉴定核苷酸进行读取测绘的改进方法。 本发明提供了在基因组中已知位置使用鉴定的核苷酸的方法，以通过排除与所鉴定的核苷酸不一致的潜在的映射或组装来指导来自该基因组的序列读数的分析。 关于受试者基因组中的多个SNP的信息用于通过基因组有向无环图（DAG）来鉴定候选路径。 序列读取被映射到候选路径。

公开(公告)号：WO2015058097A1

公开(公告)日：2015-04-23

申请号：PCT/US2014/061162

申请日：2014-10-17

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz

IPC: C12Q1/68

CPC classification number: C12Q1/6886 ,  C12Q1/6883 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/16

Abstract: The invention includes methods and systems for identifying diseased-induced mutations by producing multi-dimensional reference sequence constructs that account for variations between individuals, different diseases, and different stages of those diseases. Once constructed, these reference sequence constructs can be used to align sequence reads corresponding to genetic samples from patients suspected of having a disease, or who have had the disease and are in suspected remission. The reference sequence constructs also provide insight to the genetic progression of the disease.

Abstract translation: 本发明包括通过产生多维参考序列构建体来鉴定患病诱导突变的方法和系统，所述多维参考序列构建体考虑了个体之间的变化，不同的疾病以及这些疾病的不同阶段。 一旦构建，这些参考序列构建体可用于对准与怀疑患有疾病的患者或患有该疾病并且怀疑缓解的患者的遗传样品相对应的序列读数。 参考序列构建体还提供了对该疾病的遗传进展的洞察。

公开(公告)号：WO2015058093A1

公开(公告)日：2015-04-23

申请号：PCT/US2014/061156

申请日：2014-10-17

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz

IPC: G01N1/00

CPC classification number: G06F19/22 ,  C12Q1/6869 ,  C12Q2535/122

Abstract: The invention provides methods and system for making specific base calls at specific loci using a reference sequence construct, e.g., a directed acyclic graph (DAG) that represents known variants at each locus of the genome. Because the sequence reads are aligned to the DAG during alignment, the subsequent step of comparing a mutation, vis-a-vis the reference genome, to a table of known mutations can be eliminated. The disclosed methods and systems are notably efficient in dealing with structural variations within a genome or mutations that are within a structural variation.

Abstract translation: 本发明提供使用参考序列构建体（例如在基因组的每个基因座处表示已知变体的有向无环图（DAG））在特定基因座进行特异性碱基呼叫的方法和系统。 因为序列读取在比对期间与DAG对齐，所以可以消除将突变相对于参照基因组与已知突变表进行比较的后续步骤。 所公开的方法和系统在处理基因组内的结构变异或在结构变异内的突变中是显着的。

公开(公告)号：WO2015061103A1

公开(公告)日：2015-04-30

申请号：PCT/US2014/060690

申请日：2014-10-15

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz ,  MEYVIS, Nathan

IPC: G06F19/22

CPC classification number: G06F19/22 ,  G06F19/28

Abstract: Methods of analyzing a transcriptome that involves obtaining at least one pair of paired- end reads from a transcriptome from an organism, finding an alignment with an optimal score between a first read of the pair and a node in a directed acyclic data structure (the data structure has nodes representing RNA sequences such as exons or transcripts and edges connecting pairs of nodes), identifying candidate paths that include the node connected to a downstream node by a path having a length substantially similar to an insert length of the pair of paired-end reads, and aligning the paired-end rends to the candidate paths to determine an optimal- scoring alignment.

Abstract translation: 分析转录组的方法，其涉及从生物体获得来自转录组的至少一对配对末端读取，找到与所述对的第一次读取与有向无环数据结构中的节点之间的最佳分数的对齐（所述数据 结构具有表示RNA序列的节点，例如外显子或转录物和连接节点对的边缘），通过具有与所述成对对的插入长度基本相似的长度的路径识别包括连接到下游节点的节点的候选路径 读取并对齐配对末端渲染到候选路径以确定最佳评分对齐方式。

公开(公告)号：WO2015058120A1

公开(公告)日：2015-04-23

申请号：PCT/US2014/061198

申请日：2014-10-17

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz

IPC: C12Q1/68 ,  G01N33/53 ,  G06F19/10

CPC classification number: G06F19/22 ,  C12Q1/6869 ,  C12Q2535/122 ,  C12Q2537/165

Abstract: The invention includes methods for aligning reads (e.g., nucleic acid reads) comprising repeating sequences, methods for building reference sequence constructs comprising repeating sequences, and systems that can be used to align reads comprising repeating sequences. The method is scalable, and can be used to align millions of reads to a construct thousands of bases long. The methods and systems can additionally account for variability within a repeating sequence, or near to a repeating sequence, due to genetic mutation.

Abstract translation: 本发明包括用于对准包含重复序列的读取（例如，核酸读取）的方法，用于构建包含重复序列的参考序列构建体的方法，以及可用于对准包含重复序列的读取的系统。 该方法是可扩展的，并且可以用于将数百万个读取对齐到构建数千个基础长的构造。 由于遗传突变，方法和系统可以另外考虑重复序列内的可变性或接近重复序列的变异性。

公开(公告)号：WO2015058095A1

公开(公告)日：2015-04-23

申请号：PCT/US2014/061158

申请日：2014-10-17

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz

IPC: C12Q1/68 ,  G06F19/10

CPC classification number: G06F19/22

Abstract: The invention includes methods for aligning reads (e.g., nucleic acid reads, amino acid reads) to a reference sequence construct, methods for building the reference sequence construct, and systems that use the alignment methods and constructs to produce sequences. The invention also includes methods and systems for evaluating the quality of the alignment between the reads and the reference sequence construct. The method is scalable, and can be used to align millions of reads to a construct thousands of bases or amino acids long. The invention additionally includes methods for identifying a disease or a genotype based upon alignment of nucleic acid reads to a location in the construct.

Abstract translation: 本发明包括用于将阅读（例如，核酸读取，氨基酸读取）与参考序列构建体对准的方法，用于构建参考序列构建体的方法以及使用比对方法和构建体产生序列的系统。 本发明还包括用于评估读取和参考序列构建体之间的对准质量的方法和系统。 该方法是可扩展的，并且可以用于将数百万次读取与构建数千个碱基或氨基酸进行比较。 本发明另外包括基于核酸读取与构建体中的位置的比对来鉴定疾病或基因型的方法。

公开(公告)号：WO2015027050A1

公开(公告)日：2015-02-26

申请号：PCT/US2014/052065

申请日：2014-08-21

Applicant: SEVEN BRIDGES GENOMICS INC.

Inventor： KURAL, Deniz

IPC: C12Q1/68 ,  G01N33/574 ,  G01N33/50

CPC classification number: G06F19/22

Abstract: The invention includes methods for aligning reads (e.g., nucleic acid reads, amino acid reads) to a reference sequence construct, methods for building the reference sequence construct, and systems that use the alignment methods and constructs to produce sequences. The method is scalable, and can be used to align millions of reads to a construct thousands of bases or amino acids long. The invention additionally includes methods for identifying a disease or a genotype based upon alignment of nucleic acid reads to a location in the construct.

Abstract translation: 本发明包括用于将阅读（例如，核酸读取，氨基酸读取）与参考序列构建体对准的方法，用于构建参考序列构建体的方法以及使用比对方法和构建体产生序列的系统。 该方法是可扩展的，并且可以用于将数百万次读取与构建数千个碱基或氨基酸进行比较。 本发明另外包括基于核酸读取与构建体中的位置的比对来鉴定疾病或基因型的方法。