公开(公告)号：US20130252824A1

公开(公告)日：2013-09-26

申请号：US13793186

申请日：2013-03-11

申请人： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Johnson

发明人： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Johnson

IPC分类号： G06F19/20

CPC分类号： G06F19/20 ,  G06F19/18

摘要： A system and method for determining the genetic data for one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available, are disclosed. Genetic data for the target individual is acquired and amplified using known methods, and poorly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related subjects. In accordance with one embodiment of the invention, incomplete genetic data is acquired from embryonic cells, fetal cells, or cell-free fetal DNA isolated from the mother's blood, and the incomplete genetic data is reconstructed using the more complete genetic data from a larger sample diploid cells from one or both parents, with or without genetic data from haploid cells from one or both parents, and/or genetic data taken from other related individuals.

摘要翻译： 公开了一种用于确定一个或一小组细胞遗传数据的系统和方法，或从有限数量的遗传数据获得的片段DNA。 使用已知方法获取和扩增目标个体的遗传数据，并且使用目标基因组与基因相关受试者的基因组之间的预期相似性重建差测量的碱基对，缺失的等位基因和缺失区域。 根据本发明的一个实施方案，从母体血液中分离的胚胎细胞，胎儿细胞或无细胞胎儿DNA获得不完整的遗传数据，并且使用更大的样本的更完整的遗传数据来重建不完整的遗传数据 来自一个或两个父母的二倍体细胞，具有或不具有来自一个或两个亲本的单倍体细胞的遗传数据和/或从其他相关个体获取的遗传数据。

公开(公告)号：US20110288780A1

公开(公告)日：2011-11-24

申请号：US13110685

申请日：2011-05-18

申请人： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Zachary Demko ,  Matthew Hill ,  Bernhard Zimmermann ,  Johan Baner

发明人： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Zachary Demko ,  Matthew Hill ,  Bernhard Zimmermann ,  Johan Baner

IPC分类号： G06F19/00 ,  C07H21/04

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q2537/161 ,  C12Q2537/165 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/16 ,  C12Q2600/172 ,  G06F19/00 ,  G06F19/12 ,  G06F19/18 ,  G06F19/22 ,  G06F19/34 ,  G16H50/30

摘要： Methods for non-invasive prenatal ploidy calling are disclosed herein. Methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a sample of DNA from the mother of the fetus and from the fetus, and from genotypic data from the mother and optionally also from the father are disclosed herein. The ploidy state is determined by using a joint distribution model to create a set of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. In an embodiment, the mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias.

摘要翻译： 本文公开了非侵入性产前倍性呼叫的方法。 本文公开了从胎儿母体和胎儿的DNA样本以及来自母亲和任选也来自父亲的基因型数据测量的基因型数据中确定妊娠胎儿染色体倍性状态的方法。 通过使用联合分布模型来确定给定父母基因型数据的不同可能胎儿倍性状态的一组预期等位基因分布，并将预期等位基因分布与在混合样品中测量的测量等位基因分布的模式进行比较来确定倍性状态， 并选择其预期等位基因分布模式与观察到的等位基因分布模式最接近的倍性状态。 在一个实施方案中，DNA的混合样品可以以使等位基因偏倚最小化的方式优先富集在多个多态位点。

公开(公告)号：US20080243398A1

公开(公告)日：2008-10-02

申请号：US12076348

申请日：2008-03-17

申请人： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Scott Johnson ,  Dusan Kijacic ,  Dimitri Petrov ,  Josh Sweetkind-Singer ,  Jing Xu

发明人： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Scott Johnson ,  Dusan Kijacic ,  Dimitri Petrov ,  Josh Sweetkind-Singer ,  Jing Xu

IPC分类号： G01N33/48

CPC分类号： G06F19/16 ,  C12Q1/6855 ,  C12Q1/6874 ,  G06F19/18 ,  G06F19/24 ,  G06Q50/22

摘要： Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Genetic material from the target individual is acquired, amplified and the genetic data is measured using known methods. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment of the invention, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment of the invention, the chromosome copy number can be determined from the measured genetic data of a single or small number of cells, with or without genetic information from one or both parents. In another embodiment of the invention, these determinations are made for the purpose of embryo selection in the context of in-vitro fertilization. In another embodiment of the invention, the genetic data can be reconstructed for the purposes of making phenotypic predictions.

摘要翻译： 本文公开了一种系统和方法，用于增加测量的遗传数据的保真度，进行等位基因调用，并确定在一组或一组细胞中或从片段DNA中确定非整倍体的状态，其中有限数量的遗传数据 是可用的 获取，扩增来自目标个体的遗传物质，并使用已知方法测量遗传数据。 使用目标基因组与遗传相关个体的基因组之间的预期相似性来重建差或不正确测量的碱基对，缺失的等位基因和缺失区域。 根据本发明的一个实施方案，使用来自一个或两个亲本的二倍体细胞的较大样本的更完整的遗传数据，在多个基因座重建来自胚胎细胞的不完全遗传数据，具有或不具有来自一个的单倍体遗传数据 或双亲。 在本发明的另一个实施方案中，染色体拷贝数可以从单个或少数细胞的测量的遗传数据确定，具有或不具有来自一个或两个亲本的遗传信息。 在本发明的另一个实施方案中，这些确定是为了在体外受精的背景下进行胚胎选择的目的。 在本发明的另一个实施方案中，为了进行表型预测的目的，可以重建遗传数据。

公开(公告)号：US10017812B2

公开(公告)日：2018-07-10

申请号：US13300235

申请日：2011-11-18

申请人： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Zachary Demko ,  Matthew Hill ,  Bernhard Zimmermann ,  Johan Baner

发明人： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Zachary Demko ,  Matthew Hill ,  Bernhard Zimmermann ,  Johan Baner

IPC分类号： G01N33/48 ,  G01N31/00 ,  G06G7/48 ,  G06G7/58 ,  C12Q1/6869 ,  C12Q1/6827 ,  G06F19/18 ,  C12Q1/6883 ,  C12Q1/6862 ,  G06F19/24

CPC分类号： C12Q1/6869 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/686 ,  C12Q1/6862 ,  C12Q1/6874 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/16 ,  G06F19/34 ,  G16B20/00 ,  G16B40/00 ,  C12Q2537/161 ,  C12Q2537/165 ,  C12Q2537/143

摘要： The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a mixed sample of DNA comprising DNA from both the mother of the fetus and from the fetus, and optionally from genotypic data from the mother and father. The ploidy state is determined by using a joint distribution model to create a plurality of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. The mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias, for example using massively multiplexed targeted PCR.

公开(公告)号：US20120185176A1

公开(公告)日：2012-07-19

申请号：US13499086

申请日：2010-09-30

申请人： Matthew Rabinowitz ,  Allison Ryan ,  George Gemelos ,  Milena Banjevic ,  Zachary Demko

发明人： Matthew Rabinowitz ,  Allison Ryan ,  George Gemelos ,  Milena Banjevic ,  Zachary Demko

IPC分类号： G06F19/00

CPC分类号： G16B30/00 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/156 ,  C12Q2600/16 ,  G06N7/005 ,  G16B20/00 ,  C12Q2537/16 ,  C12Q2537/165

摘要： Disclosed herein are methods for determining the copy number of a chromosome in a fetus in the context of non-invasive prenatal diagnosis. In an embodiment, the measured genetic data from a sample of genetic material that contains both fetal DNA and maternal DNA is analyzed, along with the genetic data from the biological parents of the fetus, and the copy number of the chromosome of interest is determined. In an embodiment, the maternal serum is measured using a single-nucleotide polymorphism (SNP) microarray, along with parental genomic data, and the determination of the chromosome copy number is used to make clinical decisions pertaining to the fetus.

摘要翻译： 本文公开了用于在非侵入性产前诊断的上下文中确定胎儿中染色体的拷贝数的方法。 在一个实施方案中，分析来自含有胎儿DNA和母体DNA的遗传物质的样品的测量的遗传数据以及来自胎儿的生物亲本的遗传数据，并确定感兴趣的染色体的拷贝数。 在一个实施方案中，使用单核苷酸多态性（SNP）微阵列以及亲本基因组数据测量母体血清，并且使用染色体拷贝数的确定来进行与胎儿有关的临床决定。

公开(公告)号：US08024128B2

公开(公告)日：2011-09-20

申请号：US11004274

申请日：2004-12-03

申请人： Matthew Rabinowitz ,  Wayne Chambliss ,  John Croswell ,  Miro Sarbaev ,  Milena Banjevic

发明人： Matthew Rabinowitz ,  Wayne Chambliss ,  John Croswell ,  Miro Sarbaev ,  Milena Banjevic

IPC分类号： G01N33/50

CPC分类号： G06F19/24 ,  G06F19/18

摘要： The information management system disclosed enables caregivers to make better decisions by using aggregated data. The system enables the integration, validation and analysis of genetic, phenotypic and clinical data from multiple subjects. A standardized data model stores a range of patient data in standardized data classes comprising patient profile, genetic, symptomatic, treatment and diagnostic information. Data is converted into standardized data classes using a data parser specifically tailored to the source system. Relationships exist between standardized data classes, based on expert rules and statistical models, and are used to validate new data and predict phenotypic outcomes. The prediction may comprise a clinical outcome in response to a proposed intervention. The statistical models and methods for training those models may be input according to a standardized template. Methods are described for selecting, creating and training the statistical models to operate on genetic, phenotypic, clinical and undetermined data sets.

摘要翻译： 公开的信息管理系统使护理人员能够通过使用聚合数据做出更好的决策。 该系统能够整合，验证和分析来自多个受试者的遗传，表型和临床数据。 标准化数据模型将患者数据范围存储在包括患者概况，遗传，症状，治疗和诊断信息的标准化数据类别中。 使用专门针对源系统定制的数据解析器将数据转换为标准化数据类。 基于专家规则和统计模型，标准化数据类之间存在关系，用于验证新数据并预测表型结果。 预测可以包括响应于所提出的干预的临床结果。 可以根据标准化模板输入训练这些模型的统计模型和方法。 描述了用于选择，创建和训练统计模型以操作遗传，表型，临床和未确定数据集的方法。

公开(公告)号：US20140193816A1

公开(公告)日：2014-07-10

申请号：US14156433

申请日：2014-01-15

申请人： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Johnson

发明人： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Johnson

IPC分类号： G06F19/18

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6876 ,  C12Q2600/118 ,  C12Q2600/156 ,  C12Q2600/158 ,  G16B20/00 ,  G16B25/00 ,  G16B30/00 ,  G16B40/00 ,  C12Q2537/16 ,  C12Q2537/165

摘要： A system and method for determining the genetic data for one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available, are disclosed. Genetic data for the target individual is acquired and amplified using known methods, and poorly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related subjects. In accordance with one embodiment of the invention incomplete genetic data is acquired from embryonic cells, fetal cells, or cell-free fetal DNA isolated from the mother's blood, and the incomplete genetic data is reconstructed using the more complete genetic data from a larger sample diploid cells from one or both parents, with or without genetic data from haploid cells from one or both parents, and/or genetic data taken from other related individuals.

摘要翻译： 公开了一种用于确定一个或一小组细胞遗传数据的系统和方法，或从有限数量的遗传数据获得的片段DNA。 使用已知方法获取和扩增目标个体的遗传数据，并且使用目标基因组与基因相关受试者的基因组之间的预期相似性重建差测量的碱基对，缺失的等位基因和缺失区域。 根据本发明的一个实施方案，从母体血液中分离的胚胎细胞，胎儿细胞或无细胞胎儿DNA获得不完全遗传数据，并使用更大的样本二倍体的更完整的遗传数据重建不完全遗传数据 来自一个或两个亲本的细胞，具有或不具有来自一个或两个亲本的单倍体细胞的遗传数据，和/或从其他相关个体获取的遗传数据。

公开(公告)号：US08515679B2

公开(公告)日：2013-08-20

申请号：US12076348

申请日：2008-03-17

申请人： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Scott Johnson ,  Dusan Kijacic ,  Dimitri Petrov ,  Josh Sweetkind-Singer ,  Jing Xu

发明人： Matthew Rabinowitz ,  Milena Banjevic ,  Zachary Demko ,  David Scott Johnson ,  Dusan Kijacic ,  Dimitri Petrov ,  Josh Sweetkind-Singer ,  Jing Xu

IPC分类号： G01N33/48 ,  G01N31/00 ,  G06G7/48 ,  G06G7/58

CPC分类号： G06F19/16 ,  C12Q1/6855 ,  C12Q1/6874 ,  G06F19/18 ,  G06F19/24 ,  G06Q50/22

摘要： Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Genetic material from the target individual is acquired, amplified and the genetic data is measured using known methods. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment of the invention, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment of the invention, the chromosome copy number can be determined from the measured genetic data of a single or small number of cells, with or without genetic information from one or both parents. In another embodiment of the invention, these determinations are made for the purpose of embryo selection in the context of in-vitro fertilization. In another embodiment of the invention, the genetic data can be reconstructed for the purposes of making phenotypic predictions.

摘要翻译： 本文公开了一种系统和方法，用于增加测量的遗传数据的保真度，进行等位基因调用，并确定在一组或一组细胞中或从片段DNA中确定非整倍体的状态，其中有限数量的遗传数据 是可用的 获取，扩增来自目标个体的遗传物质，并使用已知方法测量遗传数据。 使用目标基因组与遗传相关个体的基因组之间的预期相似性来重建差或不正确测量的碱基对，缺失的等位基因和缺失区域。 根据本发明的一个实施方案，使用来自一个或两个亲本的二倍体细胞的较大样本的更完整的遗传数据，在多个基因座重建来自胚胎细胞的不完全遗传数据，具有或不具有来自一个的单倍体遗传数据 或双亲。 在本发明的另一个实施方案中，染色体拷贝数可以从单个或少数细胞的测量的遗传数据确定，具有或不具有来自一个或两个亲本的遗传信息。 在本发明的另一个实施方案中，这些确定是为了在体外受精的背景下进行胚胎选择的目的。 在本发明的另一个实施方案中，为了进行表型预测的目的，可以重建遗传数据。

公开(公告)号：US20110178719A1

公开(公告)日：2011-07-21

申请号：US13057350

申请日：2009-08-04

申请人： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Joshua Sweetkind-Singer

发明人： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Joshua Sweetkind-Singer

IPC分类号： G06F17/18 ,  G06F19/10

CPC分类号： G16B20/00 ,  C12Q1/6883 ,  C12Q2600/156 ,  G16B40/00

摘要： Disclosed herein is a system and method for making allele calls, and for determining the ploidy state, in one or a small set of cells, or where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed and the haplotypes are determined using expected similarities between the target genome and the knowledge of the genomes of genetically related individuals. In one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the genetic data from both parents, and possibly one or more sperm and/or sibling embryos. In another embodiment, the chromosome copy number can be determined using the same input data. In another embodiment, these determinations are made for embryo selection during IVF, for non-invasive prenatal diagnosis, or for making phenotypic predictions.

摘要翻译： 本文公开了一种用于在一个或一小组细胞中或其中有限数量的遗传数据可用的等位基因调用和用于确定倍性状态的系统和方法。 重建不良或不正确的碱基对，缺失的等位基因和缺失区域，并使用目标基因组与遗传相关个体基因组知识之间的预期相似性来确定单倍型。 在一个实施方案中，使用来自双亲和可能的一个或多个精子和/或同胞胚胎的遗传数据在多个基因座重建来自胚胎细胞的不完全遗传数据。 在另一个实施方案中，可以使用相同的输入数据来确定染色体拷贝数。 在另一个实施方案中，进行这些测定用于IVF期间的胚胎选择，用于非侵入性产前诊断或用于进行表型预测。

公开(公告)号：US08825412B2

公开(公告)日：2014-09-02

申请号：US13110685

申请日：2011-05-18

申请人： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Zachary Demko ,  Matthew Hill ,  Bernhard Zimmermann ,  Johan Baner

发明人： Matthew Rabinowitz ,  George Gemelos ,  Milena Banjevic ,  Allison Ryan ,  Zachary Demko ,  Matthew Hill ,  Bernhard Zimmermann ,  Johan Baner

IPC分类号： G01N33/48 ,  G06F19/00 ,  G01N31/00 ,  G06G7/48 ,  G06G7/58 ,  G06F19/12 ,  C12Q1/68

CPC分类号： C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q2537/161 ,  C12Q2537/165 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/16 ,  C12Q2600/172 ,  G06F19/00 ,  G06F19/12 ,  G06F19/18 ,  G06F19/22 ,  G06F19/34 ,  G16H50/30

摘要： Methods for non-invasive prenatal ploidy calling are disclosed herein. Methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a sample of DNA from the mother of the fetus and from the fetus, and from genotypic data from the mother and optionally also from the father are disclosed herein. The ploidy state is determined by using a joint distribution model to create a set of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. In an embodiment, the mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias.

摘要翻译： 本文公开了非侵入性产前倍性呼叫的方法。 本文公开了从胎儿母体和胎儿的DNA样本以及来自母亲和任选也来自父亲的基因型数据测量的基因型数据中确定妊娠胎儿染色体倍性状态的方法。 通过使用联合分布模型来确定给定父母基因型数据的不同可能胎儿倍性状态的一组预期等位基因分布，并将预期等位基因分布与在混合样品中测量的测量等位基因分布的模式进行比较来确定倍性状态， 并选择其预期等位基因分布模式与观察到的等位基因分布模式最接近的倍性状态。 在一个实施方案中，DNA的混合样品可以以使等位基因偏倚最小化的方式优先富集在多个多态位点。