Patents Assigned to NATERA, INC.
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Publication number: 20220033908Abstract: 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. 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, 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, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.Type: ApplicationFiled: October 15, 2021Publication date: February 3, 2022Applicant: Natera, Inc.Inventors: Matthew RABINOWITZ, Milena BANJEVIC, Zachary DEMKO, David JOHNSON, Dusan KIJACIC, Dimitri PETROV, Joshua SWEETKIND-SINGER, Jing XU
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Publication number: 20220025455Abstract: The present disclosure provides methods and compositions for sequencing nucleic acid molecules and identifying individual sample nucleic acid molecules using Molecular Index Tags (MITs). Furthermore, reaction mixtures, kits, and adapter libraries are provided.Type: ApplicationFiled: October 5, 2021Publication date: January 27, 2022Applicant: Natera, Inc.Inventors: Bernhard ZIMMERMANN, Ryan SWENERTON, Matthew RABINOWITZ, Styrmir SIGURJONSSON, George GEMELOS, Apratim GANGULY, Himanshu SETHI
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Publication number: 20220025456Abstract: 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.Type: ApplicationFiled: October 5, 2021Publication date: January 27, 2022Applicant: Natera, Inc.Inventors: Matthew RABINOWITZ, George GEMELOS, Milena BANJEVIC, Allison RYAN, Zachary DEMKO, Matthew HILL, Bernhard ZIMMERMANN, Johan BANER, Styrmir SIGURJONSSON
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Publication number: 20210398609Abstract: 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.Type: ApplicationFiled: September 2, 2021Publication date: December 23, 2021Applicant: Natera, Inc.Inventors: Styrmir SIGURJONSSON, Naresh VANKAYALAPATI, Allison RYAN, Zachary DEMKO, Milena BANJEVIC
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Patent number: 11198905Abstract: 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.Type: GrantFiled: February 20, 2020Date of Patent: December 14, 2021Assignee: Natera, Inc.Inventors: Matthew Rabinowitz, George Gemelos, Milena Banjevic, Allison Ryan, Zachary Demko, Matthew Hill, Bernhard Zimmermann, Johan Baner, Styrmir Sigurjonsson
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Patent number: 11180808Abstract: 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.Type: GrantFiled: February 12, 2014Date of Patent: November 23, 2021Assignee: Natera, Inc.Inventors: Matthew Rabinowitz, George Gemelos, Milena Banjevic, Allison Ryan, Zachary Demko, Matthew Hill, Bernhard Zimmerman, Johan Baner
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Patent number: 11180802Abstract: 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.Type: GrantFiled: February 27, 2020Date of Patent: November 23, 2021Assignee: Natera, Inc.Inventors: Matthew Rabinowitz, George Gemelos, Milena Banjevic, Allison Ryan, Zachary Demko, Matthew Hill, Bernhard Zimmermann, Johan Baner
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Publication number: 20210355536Abstract: 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.Type: ApplicationFiled: July 16, 2021Publication date: November 18, 2021Applicant: Natera, Inc.Inventors: Matthew RABINOWITZ, George GEMELOS, Milena BANJEVIC, Allison RYAN, Zachary DEMKO, Matthew HILL, Bernhard ZIMMERMANN, Johan BANER, Styrmir SIGURJONSSON
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Patent number: 11168362Abstract: The present disclosure provides methods and compositions for sequencing nucleic acid molecules and identifying individual sample nucleic acid molecules using Molecular Index Tags (MITs). Furthermore, reaction mixtures, kits, and adapter libraries are provided.Type: GrantFiled: May 21, 2019Date of Patent: November 9, 2021Assignee: Natera, Inc.Inventors: Bernhard Zimmermann, Ryan Swenerton, Matthew Rabinowitz, Styrmir Sigurjonsson, George Gemelos, Apratim Ganguly, Himanshu Sethi
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Patent number: 11155861Abstract: 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.Type: GrantFiled: April 30, 2019Date of Patent: October 26, 2021Assignee: Natera, Inc.Inventors: Matthew Rabinowitz, George Gemelos, Milena Banjevic, Allison Ryan, Zachary Demko, Matthew Hill, Bernhard Zimmermann, Johan Baner, Styrmir Sigurjonsson
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Publication number: 20210327538Abstract: A method of calling a ploidy state using a neural network includes determining, for a training sample, genetic sequencing data or genetic array data for a plurality of genetic positions, determining respective true ploidy state values for a plurality of genetic segments, each genetic segment respectively comprising at least some of the plurality of genetic positions, based on the genetic sequencing data or genetic array data, and determining a neural network comprising one or more layers for calling respective ploidy state values, the neural network defined at least in part by a plurality of weights. The method further includes iteratively modifying the weights using specific processes. The method further includes calling, for a test sample, a ploidy state for a target genetic region by propagating genetic sequencing data for the test sample or genetic array data for the test sample through the modified neural network.Type: ApplicationFiled: July 16, 2019Publication date: October 21, 2021Applicant: Natera, Inc.Inventors: Agust EGILSSON, George GEMELOS, Styrmir SIGURJONSSON
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Publication number: 20210324463Abstract: Methods for non-invasive prenatal paternity testing are disclosed herein. The method uses genetic measurements made on plasma taken from a pregnant mother, along with genetic measurements of the alleged father, and genetic measurements of the mother, to determine whether or not the alleged father is the biological father of the fetus. This is accomplished by way of an informatics based method that can compare the genetic fingerprint of the fetal DNA found in maternal plasma to the genetic fingerprint of the alleged father.Type: ApplicationFiled: May 14, 2021Publication date: October 21, 2021Applicant: Natera, Inc.Inventors: Matthew RABINOWITZ, Matthew HILL, Bernhard ZIMMERMANN, Johan BANER, George GEMELOS, Milena BANJEVIC, Allison RYAN, Styrmir SIGURJONSSON, Zachary DEMKO
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Publication number: 20210327542Abstract: 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.Type: ApplicationFiled: July 1, 2021Publication date: October 21, 2021Applicant: Natera, Inc.Inventors: Allison RYAN, Katie KOBARA, Zachary DEMKO, Susan J. GROSS
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Patent number: 11111543Abstract: 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. 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, 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, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.Type: GrantFiled: February 27, 2020Date of Patent: September 7, 2021Assignee: Natera, Inc.Inventors: Matthew Rabinowitz, Milena Banjevic, Zachary Demko, David Johnson, Dusan Kijacic, Dimitri Petrov, Joshua Sweetkind-Singer, Jing Xu
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Patent number: 11111545Abstract: 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.Type: GrantFiled: October 2, 2020Date of Patent: September 7, 2021Assignee: Natera, Inc.Inventors: Joshua Babiarz, Tudor Pompiliu Constantin, Lane A. Eubank, George Gemelos, Matthew Micah Hill, Huseyin Eser Kirkizlar, Matthew Rabinowitz, Onur Sakarya, Styrmir Sigurjonsson, Bernhard Zimmermann, Johan Baner, Allison Ryan, Milena Banjevic, Zachary Demko
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Patent number: 11111544Abstract: 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. 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, 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, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.Type: GrantFiled: March 18, 2020Date of Patent: September 7, 2021Assignee: Natera, Inc.Inventors: Matthew Rabinowitz, Milena Banjevic, Zachary Demko, David Johnson, Dusan Kijacic, Dimitri Petrov, Joshua Sweetkind-Singer, Jing Xu
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Patent number: 11098366Abstract: 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.Type: GrantFiled: July 21, 2020Date of Patent: August 24, 2021Assignee: Natera, Inc.Inventors: Matthew Rabinowitz, Matthew Micah Hill, Bernhard Zimmermann, Johan Baner, George Gemelos, Milena Banjevic, Allison Ryan, Styrmir Sigurjonsson, Zachary Demko
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Patent number: 11098365Abstract: 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.Type: GrantFiled: January 21, 2020Date of Patent: August 24, 2021Assignee: Natera, Inc.Inventors: Joshua Babiarz, Tudor Pompiliu Constantin, Lane A. Eubank, George Gemelos, Matthew Micah Hill, Huseyin Eser Kirkizlar, Matthew Rabinowitz, Onur Sakarya, Styrmir Sigurjonsson, Bernhard Zimmermann
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Publication number: 20210257048Abstract: A method for calling a mutation includes determining, for each target base of a plurality of target bases, a respective value for a background error parameter based on training data. The method further includes determining a motif-specific error model including the background error parameter by performing processes that include: identifying a respective motif for each target base of the plurality of target bases, grouping the plurality of target bases into a plurality of groups, each group corresponding to a particular motif, and determining, for each group, a respective motif-specific parameter value for the background error parameter based on the determined values for the background error parameter for the target bases included in each group. The method further includes calling a mutation using the motif-specific error model and sequencing information for a biological sample.Type: ApplicationFiled: June 12, 2019Publication date: August 19, 2021Applicant: Natera, Inc.Inventors: Bernhard ZIMMERMANN, Raheleh SALARI, Ryan SWENERTON, Dina M. HAFEZ
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Patent number: 11091804Abstract: 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.Type: GrantFiled: January 24, 2020Date of Patent: August 17, 2021Assignee: Natera, Inc.Inventors: Bernhard Zimmermann, Matthew Hill, Philippe Lacroute, Michael Dodd, Alexander Wong