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    System and methods for enhancing signal-to-noise ratios of microarray-based measurements
    6.
    发明申请
    System and methods for enhancing signal-to-noise ratios of microarray-based measurements 审中-公开
    用于增强基于微阵列的测量的信噪比的系统和方法

    公开(公告)号：US20050100939A1

    公开(公告)日：2005-05-12

    申请号：US10943752

    申请日：2004-09-17

    申请人： Eugeni Namsaraev ,  George Karlin-Neumann ,  Malek Faham ,  Maneesh Jain ,  Paul Hardenbol ,  Thomas Willis ,  Zhiyong Wang

    发明人： Eugeni Namsaraev ,  George Karlin-Neumann ,  Malek Faham ,  Maneesh Jain ,  Paul Hardenbol ,  Thomas Willis ,  Zhiyong Wang

    IPC分类号： C12Q1/68 ,  G01N20060101 ,  G01N33/48 ,  G01N33/50 ,  G06F19/00

    CPC分类号： C12Q1/6837 ,  C12Q2563/131

    摘要： The present invention provides systems and methods for large-scale genetic measurements by generating from a sample labeled target sequences whose length, orientation, label, and degree of overlap and complementarity are tailored to corresponding end-attached probes of a solid support so that signal-to-noise ratios of measurement from specifically hybridized labeled target sequences are maximized. Systems for implementing methods of the invention include a set of sample-interacting probes to produce amplicons that either each contain a segment of a target polynucleotide or an oligonucleotide tag that corresponds to a segment of a target polynucleotide, one or more solid phase supports that contain a plurality of end-attached probes, and methods of generating from sample-interacting probe amplicons from which labeled target sequences are tailored for hybridization to the solid phase supports, such as microarrays. In one aspect, labeled target sequences and end-attached probe of the solid phase supports comprise oligonucleotide tags and tag complements, respectively, selected from a minimally cross-hybridizing set.

    摘要翻译： 本发明提供了用于大规模遗传测量的系统和方法，所述系统和方法通过从样品标记的靶序列产生，所述样品标记的靶序列的长度，取向，标记，重叠度和互补度被量化到固体支持物的相应末端附接探针， 来自特异性杂交的标记靶序列的测量的信噪比最大化。 用于实施本发明方法的系统包括一组样品相互作用探针以产生扩增子，每个扩增子各含有靶多核苷酸片段或对应于靶多核苷酸片段的寡核苷酸标签，一个或多个固相载体含有 多个末端连接的探针，以及从样品相互作用的探针扩增子产生的方法，其中标记的靶序列被定制用于与固相支持物例如微阵列杂交。 在一个方面，固相载体的标记的靶序列和末端连接的探针分别包含选自最小交叉杂交组的寡核苷酸标签和标签互补物。

    Simultaneous analysis of multiple genomes
    7.
    发明申请
    Simultaneous analysis of multiple genomes 审中-公开
    同时分析多个基因组

    公开(公告)号：US20060019304A1

    公开(公告)日：2006-01-26

    申请号：US11189486

    申请日：2005-07-25

    申请人： Paul Hardenbol ,  George Karlin-Neumann ,  Thomas Willis ,  Maneesh Jain ,  Nicholas Naclerio

    发明人： Paul Hardenbol ,  George Karlin-Neumann ,  Thomas Willis ,  Maneesh Jain ,  Nicholas Naclerio

    IPC分类号： C12Q1/68 ,  G06F19/00

    CPC分类号： C12Q1/6837 ,  C12Q1/6858 ,  C12Q2537/143 ,  C12Q2525/161 ,  C12Q2533/107

    摘要： The invention provides methods for multiplexing readouts from multiple hybridization-based assays that each comprise one or more hybridization or annealing steps and one or more enzymatic processing steps. In one aspect, the invention permits simultaneously analysis of a plurality of genomes by separately hybridizing a set of probes with the different genomes to form sets of probe-genome complexes in separate reaction mixtures that are combined and enzymatically treated to form amplifiable probes. From such amplifiable probes, labeled probes are produced so that for each different locus of each different genome there is a unique labeled probe, which are then specifically hybridized to their respective complements on a microarray. In another aspect, labeled oligonucleotide tags are produced from amplifiable probes. The invention is useful in applications of multiplexed hybridization-based assays for measuring characteristics of genomic samples taken from many different individuals. By conducting hybridization steps separately on samples different individuals then combining them for enzymatic processing, one takes advantage of natural reaction rate differences between hybridization reactions and enzymatic reactions to enable analysis of products of multiple assays on a single readout platform.

    摘要翻译： 本发明提供了用于从多个基于杂交的测定中复用读出的方法，每个测序包含一个或多个杂交或退火步骤和一个或多个酶处理步骤。 一方面，本发明允许通过将一组探针与不同基因组分开杂交来同时分析多个基因组，以在组合和酶处理以形成可扩增探针的分开的反应混合物中形成探针 - 基因组复合物组。 从这样的可扩增探针中产生标记的探针，使得对于每个不同基因组的每个不同基因座，存在唯一标记的探针，然后在微阵列上与其各自的互补序列特异性杂交。 另一方面，标记的寡核苷酸标签由可扩增的探针产生。 本发明在多基于杂交的测定用于测量从许多不同个体获取的基因组样品的特征的应用中是有用的。 通过分别对样品进行杂交步骤，然后将它们组合用于酶处理，一个利用杂交反应和酶反应之间的天然反应速率差异，以使得能够在单个读出平台上分析多个测定的产物。

    Methods of monitoring conditions by sequence analysis
    9.
    发明授权
    Methods of monitoring conditions by sequence analysis 有权

    公开(公告)号：US08771954B2

    公开(公告)日：2014-07-08

    申请号：US13214111

    申请日：2011-08-19

    申请人： Malek Faham ,  Thomas Willis

    发明人： Malek Faham ,  Thomas Willis

    IPC分类号： C12Q1/68 ,  C12P19/34

    摘要： There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer. Provided herein are methods for using DNA sequencing to identify personalized biomarkers in patients with autoimmune disease and other conditions. Identified biomarkers can be used to determine the disease state for a subject with an autoimmune disease or other condition.

    DETECTING DISEASE-CORRELATED CLONOTYPES FROM FIXED SAMPLES
    10.
    发明申请
    DETECTING DISEASE-CORRELATED CLONOTYPES FROM FIXED SAMPLES 审中-公开
    从固定样品中检测疾病相关的克隆

    公开(公告)号：US20130324422A1

    公开(公告)日：2013-12-05

    申请号：US13487980

    申请日：2012-06-04

    申请人： Malek Faham ,  Thomas Willis

    发明人： Malek Faham ,  Thomas Willis

    IPC分类号： C40B20/04 ,  C12Q1/68

    CPC分类号： C07K16/00

    摘要： The invention is directed to a method for determining immunophenotypes of tissue-infiltrating lymphocytes in a solid tissue of a patient by (a) generating clonotype profiles from a sample of nucleic acid extracted from a fixed tissue sample from a solid tissue of the patient, where such tissue contains tissue-infiltrating lymphocytes; and (b) determining immunophenotypes of the tissue-infiltrating lymphocytes by (i) obtaining a sample of lymphocytes from peripheral blood of the patient; (ii) sorting the lymphocytes from peripheral blood into at least one subset based on different immunophenotypes of the lymphocytes; (iii) generating a clonotype profile for each of the at least one subset of lymphocytes; and (iv) determining immunophenotypes of lymphocytes in the fixed tissue sample by a correspondence between clonotypes of the fixed tissue sample and clonotypes of the at least one subset.

    摘要翻译： 本发明涉及一种用于通过（a）从来自患者的固体组织的固定组织样品提取的核酸样品产生克隆型谱的方法，用于确定患者的固体组织中组织浸润淋巴细胞的免疫表型，其中 这种组织含有组织浸润淋巴细胞; （b）通过（i）从患者的外周血中获得淋巴细胞的样品来确定组织浸润淋巴细胞的免疫表型; （ii）基于淋巴细胞的不同免疫表型将淋巴细胞从外周血分离成至少一个亚组; （iii）产生淋巴细胞的至少一个子集中的每一个的克隆型谱; 和（iv）通过所述固定组织样品的克隆型与所述至少一个亚组的克隆型之间的对应关系确定所述固定组织样品中淋巴细胞的免疫表型。