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    • 3. 发明申请
    • NUCLEIC ACID ANALYSIS BY RANDOM MIXTURES OF NON-OVERLAPPING FRAGMENTS
    • 非叠加片段随机混合物的核酸分析
    • WO2006138284A3
    • 2007-12-13
    • PCT/US2006022950
    • 2006-06-13
    • CALLIDA GENOMICS INCDRMANAC RADOJE
    • DRMANAC RADOJE
    • C12Q1/68C07H21/02
    • C12Q1/6874C07H21/04C07K1/047C12Q1/6806C12Q1/682C12Q1/6837C12Q1/6869C12Q2525/151C12Q2525/313C12Q2531/125C12Q2565/513G01N15/1404G01N15/1434Y10S977/778Y10S977/789Y10S977/792Y10S977/88Y10S977/882C12Q2521/307C12Q2525/161C12Q2535/122C12Q2563/179C12Q2565/514
    • The invention provides methods and kits for ordering sequence information derived from one or more target polynucleotides. In one aspect, one or more tiers or levels of fragmentation and aliquoting are generated, after which sequence information is obtained from fragments in a final level or tier. Each fragment in such final tier is from a particular aliquot, which, in turn, is from a particular aliquot of a prior tier, and so on. For every fragment of an aliquot in the final tier, the aliquots from which it was derived at every prior tier is known, or can be discerned. Thus, identical sequences from overlapping fragments from different aliquots can be distinguished and grouped as being derived from the same or different fragments from prior tiers. When the fragments in the final tier are sequenced, overlapping sequence regions of fragments in different aliquots are used to register the fragments so that non-overlapping regions are ordered. In one aspect, this process is carried out in a hierarchical fashion until the one or more target polynucleotides are characterized, e.g. by their nucleic acid sequences, or by an ordering of sequence segments, or by an ordering of single nucleotide polymorphisms (SNPs), or the like.
    • 本发明提供了用于排序从一个或多个目标多核苷酸衍生的序列信息的方法和试剂盒。 在一个方面,产生一个或多个分层或等级的碎片和等分试样,之后从最终级别或层级的片段获得序列信息。 这样的最后一层中的每个片段都来自特定的等分试样,反过来,这些等分试样来自先前层的特定等分试样,依此类推。 对于最后一层中的等分试样的每个片段,从每个先前的层次派生的等分试样是已知的,或者可以被辨别出来。 因此,来自不同等分试样的重叠片段的相同序列可以被区分并分组为从与先前层相同或不同的片段衍生的。 当最终层中的片段被排序时,使用不同等分试样的片段的重叠序列区域来登记片段,使得非重叠区域被排序。 在一个方面,该方法以分级方式进行,直到一个或多个目标多核苷酸被表征为例如。 通过其核酸序列,或通过序列片段的排序,或通过单核苷酸多态性(SNP)等的排序。
    • 4. 发明申请
    • HIGH THROUGHPUT GENOME SEQUENCING ON DNA ARRAYS
    • 在DNA阵列上测序的高通量基因
    • WO2007133831A3
    • 2008-02-07
    • PCT/US2007062825
    • 2007-02-26
    • COMPLETE GENOMICS INCDRMANAC RADOJECALLOW MATTHEW JDRMANAC SNEZANA
    • DRMANAC RADOJECALLOW MATTHEW JDRMANAC SNEZANA
    • C12Q1/68C07H21/04
    • C12Q1/6837C12Q1/6874C12Q2531/125C12Q2525/151C12Q2521/313
    • The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences using adaptors interspersed in target polynucleotides. The sequence information can be new. e.g. sequencing unknown nucleic acids, re-sequencing, or genotyping. The invention preferably includes methods for inserting a plurality of adaptors at spaced locations within a target polynucleotide or a fragment of a polynucleotide. Such adaptors may serve as platforms for interrogating adjacent sequences using various sequencing chemistries, such as those that identify nucleotides by primer extension, probe ligation, and the like. Encompassed in the invention are methods and compositions for the insertion of known adaptor sequences into target sequences, such that there is an interruption of contiguous target sequence with the adaptors. By sequencing both "upstream" and "downstream" of the adaptors, identification of entire target sequences may be accomplished.
    • 本发明涉及使用分散在靶多核苷酸中的衔接子获得靶序列的核苷酸序列信息的方法和组合物。 序列信息可以是新的。 例如 测序未知核酸,重新测序或基因分型。 本发明优选地包括在多核苷酸的靶多核苷酸或片段内的间隔位置插入多个衔接子的方法。 这样的衔接子可以用作使用各种测序化学品询问相邻序列的平台,例如通过引物延伸,探针连接等鉴定核苷酸的测序化学物质。 在本发明中包括用于将已知衔接子序列插入靶序列的方法和组合物,使得与适配器存在连续靶序列的中断。 通过对适配器的“上游”和“下游”进行排序,可以完成整个靶序列的识别。
    • 9. 发明申请
    • EFFICIENT SHOTGUN SEQUENCING METHODS
    • 有效的SHOTGUN测序方法
    • WO2009073629A2
    • 2009-06-11
    • PCT/US2008085189
    • 2008-12-01
    • COMPLETE GENOMICS INCDRMANAC RADOJEREID CLIFFORD
    • DRMANAC RADOJEREID CLIFFORD
    • C12Q1/68
    • C12Q1/6869C12Q1/6874C12Q2549/119C12Q2537/149C12Q2565/137
    • Methods are provided for efficient shotgun sequencing to allow efficient selection and sequencing of nucleic acids of interest contained in a library. The nucleic acids of interest can be defined any time before or after preparation of the library. One example of nucleic acids of interest is missing or low confidence genome sequences resulting from an initial sequencing procedure. Other nucleic acids of interest include subsets of genomic DNA, RNA or cDNAs (exons, genes, gene sets, transciptomes). By designing an efficient (simple to implement, speedy, high specificity, low cost) selection procedure, a more complete sequence is achieved with less effort than by using highly redundant shotgun sequencing in an initial sequencing procedure
    • 提供了用于有效鸟枪法测序的方法,以允许对库中所含目的核酸进行有效选择和测序。 感兴趣的核酸可以在文库制备之前或之后的任何时候定义。 感兴趣的核酸的一个例子是由初始测序程序产生的缺失或低置信度的基因组序列。 其他感兴趣的核酸包括基因组DNA,RNA或cDNA(外显子,基因,基因组,转座体)的亚组。 通过设计一个有效的(简单实施,快速,高特异性,低成本)选择程序,以比在初始测序程序中使用高度冗余鸟枪法测序更少的努力实现更完整的序列