公开(公告)号：US20180073080A1

公开(公告)日：2018-03-15

申请号：US15806047

申请日：2017-11-07

Applicant: Natera, Inc.

Inventor： Matthew RABINOWITZ ,  George GEMELOS ,  Milena BANJEVIC ,  Allison RYAN ,  Zachary DEMKO ,  Matthew HILL ,  Bernhard ZIMMERMANN ,  Johan BANER

IPC: C12Q1/68 ,  G06F19/12 ,  G06F19/18 ,  G06F19/22 ,  G06F19/00

CPC classification number: C12Q1/6883 ,  C12Q1/6827 ,  C12Q1/6869 ,  C12Q2537/161 ,  C12Q2537/165 ,  C12Q2600/112 ,  C12Q2600/156 ,  C12Q2600/16 ,  C12Q2600/172 ,  G06F19/34 ,  G16B5/00 ,  G16B20/00 ,  G16B30/00 ,  G16H50/30

Abstract: The present disclosure provides 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. 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.

公开(公告)号：US20240301482A1

公开(公告)日：2024-09-12

申请号：US18441502

申请日：2024-02-14

Applicant: Natera, Inc.

Inventor： Huseyin Eser KIRKIZLAR ,  Raheleh SALARI ,  Stymir SIGURJONSSON ,  Bernhard ZIMMERMANN ,  Allison RYAN ,  Naresh VANKAYALAPATI

IPC: C12Q1/6858 ,  C12Q1/6853 ,  C12Q1/6869 ,  C12Q1/6886 ,  G16B20/00 ,  G16B20/10 ,  G16H10/40

CPC classification number: C12Q1/6858 ,  C12Q1/6853 ,  C12Q1/6869 ,  C12Q1/6886 ,  G16B20/00 ,  G16B20/10 ,  G16H10/40 ,  C12Q2539/10 ,  C12Q2600/106 ,  C12Q2600/156 ,  Y02A90/10

Abstract: The invention provides improved methods, compositions, and kits for detecting ploidy of chromosome regions, e.g. for detecting cancer or a chromosomal abnormality in a gestating fetus. The methods can utilize a set of more than 200 SNPs that are found within haploblocks and can include analyzing a series of target chromosomal regions related to cancer or a chromosomal abnormality in a gestating fetus. Finally the method may use knowledge about chromosome crossover locations or a best fit algorithm for the analysis. The compositions may comprise more than 200 primers located within haplotype blocks known to show CNV.

公开(公告)号：US20240068031A1

公开(公告)日：2024-02-29

申请号：US18243593

申请日：2023-09-07

Applicant: Natera, Inc.

Inventor： Matthew RABINOWITZ ,  Matthew HILL ,  Bernhard ZIMMERMANN ,  George GEMELOS ,  Johan BANER ,  Milena BANJEVIC ,  Allison RYAN ,  Styrmir SIGURJONSSON ,  Zachary DEMKO

IPC: C12Q1/6883 ,  C12Q1/6809 ,  C12Q1/6811 ,  C12Q1/6844 ,  C12Q1/6848 ,  C12Q1/6851 ,  C12Q1/6855 ,  C12Q1/6869 ,  C12Q1/6874

CPC classification number: C12Q1/6883 ,  C12Q1/6809 ,  C12Q1/6811 ,  C12Q1/6844 ,  C12Q1/6848 ,  C12Q1/6851 ,  C12Q1/6855 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q2600/156

Abstract: The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

公开(公告)号：US20240062846A1

公开(公告)日：2024-02-22

申请号：US18371373

申请日：2023-09-21

Applicant: Natera, Inc.

Inventor： Matthew RABINOWITZ ,  George GEMELOS ,  Milena BANJEVIC ,  Allison RYAN ,  Zachary DEMKO ,  Matthew HILL ,  Bernhard ZIMMERMANN ,  Johan BANER

IPC: G16B20/00 ,  C12Q1/6827 ,  C12Q1/6862 ,  C12Q1/686 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  C12Q1/6883 ,  C12Q1/6869 ,  C12Q1/6806 ,  C12Q1/6874

CPC classification number: G16B20/00 ,  C12Q1/6827 ,  C12Q1/6862 ,  C12Q1/686 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  C12Q1/6883 ,  C12Q1/6869 ,  C12Q1/6806 ,  C12Q1/6874 ,  G16B40/00

Abstract: 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：US20230383348A1

公开(公告)日：2023-11-30

申请号：US18126344

申请日：2023-03-24

Applicant: Natera, Inc.

Inventor： Matthew RABINOWITZ ,  Matthew HILL ,  Bernhard ZIMMERMANN ,  George GEMELOS ,  Johan BANER ,  Milena BANJEVIC ,  Allison RYAN ,  Styrmir SIGURJONSSON ,  Zachary DEMKO

IPC: C12Q1/6883 ,  C12Q1/6811 ,  C12Q1/6848 ,  C12Q1/6809 ,  C12Q1/6851 ,  C12Q1/6844 ,  C12Q1/6869 ,  C12Q1/6855 ,  C12Q1/6874

CPC classification number: C12Q1/6883 ,  C12Q1/6811 ,  C12Q1/6848 ,  C12Q1/6809 ,  C12Q1/6851 ,  C12Q1/6844 ,  C12Q1/6869 ,  C12Q1/6855 ,  C12Q1/6874 ,  C12Q2600/156

Abstract: The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

公开(公告)号：US20230360723A1

公开(公告)日：2023-11-09

申请号：US18227219

申请日：2023-07-27

Applicant: Natera, Inc.

Inventor： Matthew RABINOWITZ ,  George GEMELOS ,  Milena BANJEVIC ,  Allison RYAN ,  Zachary DEMKO ,  Matthew HILL ,  Bernhard ZIMMERMANN ,  Johan BANER

IPC: G16B20/00 ,  C12Q1/6827 ,  C12Q1/6862 ,  C12Q1/686 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  C12Q1/6883 ,  C12Q1/6869 ,  C12Q1/6806 ,  C12Q1/6874

CPC classification number: G16B20/00 ,  C12Q1/6827 ,  C12Q1/6862 ,  C12Q1/686 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  C12Q1/6883 ,  C12Q1/6869 ,  C12Q1/6806 ,  C12Q1/6874 ,  G16B40/00

Abstract: 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：US20220139495A1

公开(公告)日：2022-05-05

申请号：US17573520

申请日：2022-01-11

Applicant: Natera, Inc.

Inventor： Matthew RABINOWITZ ,  George GEMELOS ,  Milena BANJEVIC ,  Allison RYAN ,  Zachary DEMKO ,  Matthew HILL ,  Bernhard ZIMMERMANN ,  Johan BANER ,  Styrmir SIGURJONSSON

IPC: G16B20/00 ,  G16B20/20 ,  G16B20/40 ,  G16B20/10 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/686 ,  C12Q1/6862 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q1/6883

Abstract: 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：US20220025456A1

公开(公告)日：2022-01-27

申请号：US17494745

申请日：2021-10-05

Applicant: Natera, Inc.

Inventor： Matthew RABINOWITZ ,  George GEMELOS ,  Milena BANJEVIC ,  Allison RYAN ,  Zachary DEMKO ,  Matthew HILL ,  Bernhard ZIMMERMANN ,  Johan BANER ,  Styrmir SIGURJONSSON

IPC: C12Q1/6869 ,  G16B20/00 ,  C12Q1/6827 ,  C12Q1/6862 ,  C12Q1/686 ,  G16B20/10 ,  G16B20/20 ,  G16B20/40 ,  C12Q1/6883 ,  C12Q1/6806 ,  C12Q1/6874

Abstract: 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：US20210398609A1

公开(公告)日：2021-12-23

申请号：US17465424

申请日：2021-09-02

Applicant: Natera, Inc.

Inventor： Styrmir SIGURJONSSON ,  Naresh VANKAYALAPATI ,  Allison RYAN ,  Zachary DEMKO ,  Milena BANJEVIC

IPC: G16B20/10 ,  G16B30/00 ,  G16B5/00 ,  G16B20/00 ,  G16B5/20

Abstract: Provided herein are improved methods for detecting aneuploidy in a sample. The methods in certain embodiments are used for the analysis of circulating DNA in serum samples, such as circulating fetal DNA or circulating tumor DNA. In certain embodiments, chromosome or chromosome segments of interest are used to set a bias model and/or a control value for a z-score determination, in illustrative examples without the use of a control chromosome.

公开(公告)号：US20210327542A1

公开(公告)日：2021-10-21

申请号：US17365786

申请日：2021-07-01

Applicant: Natera, Inc.

Inventor： Allison RYAN ,  Katie KOBARA ,  Zachary DEMKO ,  Susan J. GROSS

IPC: G16B40/00 ,  C12Q1/6869 ,  G16B20/00

Abstract: Disclosed herein are system, method, and computer program product embodiments for determining aneuploidy risk in a target sample of maternal blood or plasma based on the amount of fetal DNA. An embodiment operates by receiving known genetic data from known prenatal testing samples and genetic data for the target sample. A fetal fraction distribution is determined for the known genetic data based on gestational age and the maternal weight associated with the target sample. A model is then generated based on a fixed ratio reduction of the determined fetal fraction distribution. A fetal fraction based data likelihood for the target sample is then determined for each of the plurality of ploidy states using the generated model. An aneuploidy risk score is then outputted based on applying a Bayesian probability determination that combines each fetal fraction based data likelihood with a previously determined risk score as a conditional value.