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1. 发明申请

US20150167080A1 METHOD OF DETERMINING CLONOTYPES AND CLONOTYPE PROFILES 有权
标题翻译：确定克隆和克隆型材的方法
公开(公告)号：US20150167080A1
公开(公告)日：2015-06-18
申请号：US13196885
申请日：2011-08-02
申请人： Martin Moorhead , Malek Faham , Thomas Willis
发明人： Martin Moorhead , Malek Faham , Thomas Willis
IPC分类号： C12Q1/68 , C40B20/00
CPC分类号： C12Q1/6881 , C12Q1/6883 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16 , G06F19/14 , G06F19/22
摘要： The invention is directed to methods for determining clonotypes and clonotype profiles in assays for analyzing immune repertoires by high throughput nucleic acid sequencing of somatically recombined immune molecules. In one aspect, the invention comprises generating a clonotype profile from an individual by generating sequence reads from a sample of recombined immune molecules; forming from the sequence reads a sequence tree representing candidate clonotypes each having a frequency; coalescing with a highest frequency candidate clonotype any lesser frequency candidate clonotypes whenever such lesser frequency is below a predetermined value and whenever a sequence difference therebetween is below a predetermined value to form a clonotype. After such coalescence, the candidate clonotypes is removed from the sequence tree and the process is repeated. This approach permits rapid and efficient differentiation of candidate clonotypes with genuine sequence differences from those with experimental or measurement errors, such as sequencing errors.
摘要翻译：本发明涉及用于通过体细胞重组的免疫分子的高通量核酸测序分析免疫谱的测定中的克隆型和克隆型谱的方法。在一个方面，本发明包括通过从重组的免疫分子的样品产生序列读数来从个体产生克隆型谱; 从序列形成读取表示每个具有频率的候选克隆型的序列树; 每当这样较小的频率低于预定值，并且每当它们之间的序列差异低于预定值以形成克隆型时，以最高频率候选克隆型任何较低频率候选克隆型聚合。在这样的聚结之后，从序列树中移除候选克隆型，并重复该过程。这种方法允许用具有实验或测量误差（例如测序错误）的那些具有真正序列差异的候选克隆型的快速和有效的分化。

2. 发明授权

US09043160B1 Method of determining clonotypes and clonotype profiles 有权
标题翻译：确定克隆型和克隆型谱的方法
公开(公告)号：US09043160B1
公开(公告)日：2015-05-26
申请号：US13196885
申请日：2011-08-02
申请人： Martin Moorhead , Malek Faham , Thomas Willis
发明人： Martin Moorhead , Malek Faham , Thomas Willis
IPC分类号： G06F7/00 , G06F19/14
CPC分类号： C12Q1/6881 , C12Q1/6883 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16 , G06F19/14 , G06F19/22
摘要： The invention is directed to methods for determining clonotypes and clonotype profiles in assays for analyzing immune repertoires by high throughput nucleic acid sequencing of somatically recombined immune molecules. In one aspect, the invention comprises generating a clonotype profile from an individual by generating sequence reads from a sample of recombined immune molecules; forming from the sequence reads a sequence tree representing candidate clonotypes each having a frequency; coalescing with a highest frequency candidate clonotype any lesser frequency candidate clonotypes whenever such lesser frequency is below a predetermined value and whenever a sequence difference therebetween is below a predetermined value to form a clonotype. After such coalescence, the candidate clonotypes is removed from the sequence tree and the process is repeated. This approach permits rapid and efficient differentiation of candidate clonotypes with genuine sequence differences from those with experimental or measurement errors, such as sequencing errors.
摘要翻译：本发明涉及用于通过体细胞重组的免疫分子的高通量核酸测序分析免疫谱的测定中的克隆型和克隆型谱的方法。在一个方面，本发明包括通过从重组的免疫分子的样品产生序列读数来从个体产生克隆型谱; 从序列形成读取表示每个具有频率的候选克隆型的序列树; 每当这样较小的频率低于预定值，并且每当它们之间的序列差异低于预定值以形成克隆型时，以最高频率候选克隆型任何较低频率候选克隆型聚合。在这样的聚结之后，从序列树中移除候选克隆型，并重复该过程。这种方法允许用具有实验或测量误差（例如测序错误）的那些具有真正序列差异的候选克隆型的快速和有效的分化。

3. 发明授权

US08691510B2 Sequence analysis of complex amplicons 有权
标题翻译：复合扩增子的序列分析
公开(公告)号：US08691510B2
公开(公告)日：2014-04-08
申请号：US13100389
申请日：2011-05-04
申请人： Malek Faham , Martin Moorhead , Thomas Willis
发明人： Malek Faham , Martin Moorhead , Thomas Willis
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6881 , C12Q1/6874 , C12Q1/6883 , C12Q2600/158 , C12Q2600/16
摘要： The invention is directed to methods of generating sequence profiles of populations of nucleic acids, whose member nucleic acids contain regions of high variability, such as populations of nucleic acids encoding T cell receptors or B cell receptors. In one aspect, the invention provides pluralities of sets of primers for generating nested sets of templates from nucleic acids in such populations, thereby insuring the production of at least one template from which sequence reads are generated, despite such variability, or dispite limited lengths or quality of sequence reads. In another aspect, members of such populations are bidirectionally sequenced so that further sequence information is obtained by analyzing overlapping sequence reads in the zones of highest variability.
摘要翻译：本发明涉及产生核酸群体序列谱的方法，该核酸的成员核酸含有高度变异性的区域，例如编码T细胞受体或B细胞受体的核酸群体。在一个方面，本发明提供了多组引物，用于从这些群体中的核酸产生嵌套的模板集合，从而确保产生序列读取的至少一个模板的产生，尽管存在这种变化，或者限制长度或序列读取的质量。在另一方面，这些群体的成员被双向排序，以便通过分析最高变异性区域中的重叠序列读数来获得进一步的序列信息。

4. 发明申请

US20110207135A1 METHODS OF MONITORING CONDITIONS BY SEQUENCE ANALYSIS 有权
标题翻译：通过序列分析监测条件的方法
公开(公告)号：US20110207135A1
公开(公告)日：2011-08-25
申请号：US13100389
申请日：2011-05-04
申请人： Malek Faham , Martin Moorhead , Thomas Willis
发明人： Malek Faham , Martin Moorhead , Thomas Willis
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6881 , C12Q1/6874 , C12Q1/6883 , C12Q2600/158 , C12Q2600/16
摘要： The invention is directed to methods of generating sequence profiles of populations of nucleic acids, whose member nucleic acids contain regions of high variability, such as populations of nucleic acids encoding T cell receptors or B cell receptors. In one aspect, the invention provides pluralities of sets of primers for generating nested sets of templates from nucleic acids in such populations, thereby insuring the production of at least one template from which sequence reads are generated, despite such variability, or dispite limited lenghs or quality of sequence reads. In another aspect, members of such populations are bidirectionally sequenced so that further sequence information is obtained by analyzing overlapping sequence reads in the zones of highest variability.
摘要翻译：本发明涉及产生核酸群体序列谱的方法，该核酸的成员核酸含有高度变异性的区域，例如编码T细胞受体或B细胞受体的核酸群体。在一个方面，本发明提供了多组引物，用于从这些群体中的核酸产生嵌套的模板集合，从而确保产生序列读数的至少一个模板的产生，尽管存在这种可变性，或者排除有限的长度或序列读取的质量。在另一方面，这些群体的成员被双向排序，以便通过分析最高变异性区域中的重叠序列读数来获得进一步的序列信息。

5. 发明申请

US20150247201A1 PREDICTING RELAPSE OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS TREATED BY ALLOGENEIC STEM CELL TRANSPLANTATION 审中-公开
标题翻译：慢性淋巴细胞移植治疗慢性淋巴细胞白血病患者预后的相关性
公开(公告)号：US20150247201A1
公开(公告)日：2015-09-03
申请号：US14404435
申请日：2013-05-30
申请人： Malek Faham , Victoria Carlton , Martin Moorhead , Francois Pepin
发明人： Malek Faham , Victoria Carlton , Martin Moorhead , Francois Pepin
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/118 , C12Q2600/158 , C12Q2600/16
摘要： The invention is directed to a prognostic indicator for CLL patients who have undergone an allogeneic stem cell transplant (SCT). The indicator is based on a method of monitoring levels and changes in levels of correlating clonotypes of the CLLs at successive time points. The prognostic indicator applies to patients who have survived for at least one year from an allogeneic SCT and includes criteria based on the following two measurements: (a) frequency of CLL correlating clonotypes (e.g. in terms of number per 106 clonotypes) in an initial clonotype profile (from peripheral blood), and (b) fold change in such CLL correlating clonotype number between such initial measurement and a successively measured clonotype profile.
摘要翻译：本发明涉及经历同种异体干细胞移植（SCT）的CLL患者的预后指标。该指标基于在连续时间点监测CLL相关性克隆型水平和水平变化的方法。预后指标适用于从同种异体SCT生存至少一年的患者，并包括基于以下两个测量的标准：（a）CLL相关克隆型（例如，以106个克隆型的数目）在初始克隆型中的频率（来自外周血），和（b）在这种初始测量和连续测量的克隆型分布之间的这种CLL相关克隆型号的倍数变化。

6. 发明申请

US20130196328A1 RARE CLONOTYPES AND USES THEREOF 有权
标题翻译：罕见的克隆及其用途
公开(公告)号：US20130196328A1
公开(公告)日：2013-08-01
申请号：US13834794
申请日：2013-03-15
申请人： Francois Pepin , Malek Faham , Martin Moorhead
发明人： Francois Pepin , Malek Faham , Martin Moorhead
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6883 , C12Q2600/158
摘要： The invention is directed to a method of selecting disease-correlated clonotypes that have a reduced likelihood of producing a false positive signal of relapse when, used to monitor minimal residual disease. In accordance with the invention, candidate correlating clonotype are obtained from a patient, the rarity of each is determined either by comparison with a clonotype database or a clonotype model, and one or more of the rarest of such clonotypes are used to monitor the minimal residual disease.
摘要翻译：本发明涉及一种选择疾病相关性克隆型的方法，所述疾病相关性克隆型在用于监测最小残留疾病时具有降低的产生假阳性信号的可能性。根据本发明，从患者获得候选相关克隆型，通过与克隆型数据库或克隆型模型比较来确定每个的罕见性，并且使用一种或多种最稀有的这种克隆型来监测最小残留疾病。

7. 发明申请

US20070065865A1 Polymorphisms Associated with Coronary Artery Disease 审中-公开
标题翻译：与冠状动脉疾病相关的多态性
公开(公告)号：US20070065865A1
公开(公告)日：2007-03-22
申请号：US11530407
申请日：2006-09-08
申请人： Victoria Carlton , Martin Moorhead , Chunnuan Chen , Malek Faham
发明人： Victoria Carlton , Martin Moorhead , Chunnuan Chen , Malek Faham
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/156
摘要： The invention provides human polymorphisms that are associated with coronary artery disease (CAD). Polymorphisms in genes were identified that confer an increased susceptibility to CAD or a decreased susceptibility. Particular alleles of the polymorphisms were identified as being associated with differential risk. In particular an allele of CDC42 in combination with an allele of PARD3 was shown to confer increased risk of CAD.
摘要翻译：本发明提供与冠状动脉疾病（CAD）相关的人多态性。鉴定出基因多态性导致对CAD的敏感性增加或易感性降低。多态性的特定等位基因被鉴定为与差异风险相关。特别地，CDC42与PARD3的等位基因组合的等位基因被证明具有增加的CAD风险。

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