Abstract

Systems and methods are provided herein for preparing a non-naturally-occurring preparation of DNA from perfusion fluid or flush, the preparation being useful for assessing transplantation outcomes of a donor organ or donor tissue which was perfused with the perfusion fluid or prepared for transplantation with flush. The preparation may also be useful for evaluating quality of the organ or tissue. Analysis of the DNA may be used to make clinical decisions. Analysis of the DNA may also be used for adaptive control of a mechanical perfusion system used for preserving the organ or tissue, by generating and executing appropriate parameter adjustments based on characteristics of the sampled DNA.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

The present disclosure provides methods for preparation and analysis of biological samples of maternal transplant recipients, wherein the methods comprise extracting cell-free DNA from the recipient, wherein the cell-free DNA comprises donor-derived cell-free DNA, recipient-derived cell-free DNA, and fetal-derived cell-free DNA, and measuring amounts of cell-free DNA and donor-derived cell-free DNA enables assessment of transplant rejection. The detection of the donor-derived cell-free DNA may be performed based on loci at which the maternal transplant recipient and biological father of the fetus are homozygous and the transplant donor is heterozygous.

IPC Classes  ?

• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection

Abstract

The present disclosure provides methods for preparation and analysis of biological samples of xenotransplant recipients, wherein the methods comprise extracting fragmented or intact cell-free DNA, RNA (such as mRNA or miRNA), or protein derived from sample of the xenotransplant recipient, and measuring amounts of cell-free DNA, RNA (such as mRNA or miRNA), or protein derived from the xenotransplant enables assessment of xenotransplant rejection. The detection of the cell-free DNA, or RNA may be performed by preparing sequencing libraries and performing whole genome sequencing.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• G01N 33/53 - Immunoassay; Biospecific binding assay; Materials therefor

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

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.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6862 - Ligase chain reaction [LCR]
• C12Q 1/686 - Polymerase chain reaction [PCR]
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Abstract

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.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 10/00 - ICT specially adapted for evolutionary bioinformatics, e.g. phylogenetic tree construction or analysis

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.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6862 - Ligase chain reaction [LCR]
• C12Q 1/686 - Polymerase chain reaction [PCR]
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Abstract

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12Q 1/6869 - Methods for sequencing

Abstract

Provided herein are compositions to be used as a positive control for detection of one or more microdeletions of interest in a sample. The positive control can be used to determine an error and an efficiency rate for assays used to identify microdeletions such as 22ql 1.2 deletion (DiGeorge syndrome), chromosome 5pl5.2 (Cri-du-chat), lp36 deletion, 15ql l.2~ql3 deletion (Prader-Willi syndrome), and/or 15ql l~ql3 (Angelman syndrome).

IPC Classes  ?

• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• C12Q 1/6851 - Quantitative amplification

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.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6862 - Ligase chain reaction [LCR]
• C12Q 1/686 - Polymerase chain reaction [PCR]
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Abstract

The present disclosure provides methods for preparation and analysis of biological samples of transplant recipients or subjects suffering from a disease or disorder, wherein the methods comprise extracting fragmented or intact RNA (such as mRNA or miRNA) derived from sample of the transplant recipient or subject suffering from a disease or disorder, wherein the extracted RNA comprises target RNA molecules preselected to enable assessment of transplant rejection. The detection of the target RNA molecules and total amount of RNA derived from the donor organ can be used to determine and/or monitoring transplant rejection.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Goods & Services

Downloadable software, namely, downloadable software for recording and managing data for clinical studies; software for gathering, storage, and evaluation of data from clinical studies Database management; collection and compilation of information into computer databases in the field of medicine and healthcare; collection and systematization of information into computer databases; business consulting and management in the field of clinical trials, namely, management and compilation of computerized databases in the field of clinical trials for business purposes; providing medical and scientific research information in the field of clinical trials; medical and scientific research, namely, conducting clinical trials for others Database design and development; compiling data for research purposes in the field of medical science; providing medical and scientific research information in the field of clinical trials; scientific and technical consulting services in the fields of clinical research, clinical study design, clinical trial design, development and implementation; providing temporary use of web-based software for recording and managing data for clinical studies; providing temporary use of web-based software for gathering, storage, and evaluation of data from clinical studies

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.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6862 - Ligase chain reaction [LCR]
• C12Q 1/686 - Polymerase chain reaction [PCR]
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

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.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6862 - Ligase chain reaction [LCR]
• C12Q 1/686 - Polymerase chain reaction [PCR]
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

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.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6862 - Ligase chain reaction [LCR]
• C12Q 1/686 - Polymerase chain reaction [PCR]
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Abstract

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.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay

Abstract

Disclosed is an approach that may include generating and/or using a predictive machine learning classifier comprising one or more artificial neural networks. The classifier is configured to output a prediction related to developing preeclampsia (e.g., early onset preterm preeclampsia) during a current pregnancy of a patient based on health characteristics and one or more DNA metrics. The health characteristics and DNA metrics, such as total cell-free DNA (cfDNA) and fetal fraction (FF), may be obtained during a routine and non-invasive or minimally-invasive prenatal screening. The predictive machine learning classifier may be generated by applying deep learning techniques to data on subjects in a cohort. The data may comprise features corresponding to outcomes of prior pregnancies, health indicators, and one or more cfDNA measurements. First trimester risk assessment for preterm preeclampsia can identify patients most likely to benefit from preventative treatment protocols with a minimal or low level of intervention.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 40/20 - Supervised data analysis
• G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment

Abstract

The present disclosure provides methods for determining the status of an allograft within a transplant recipient from genotypic data measured from a mixed sample of DNA comprising DNA from both the transplant recipient and from the donor. 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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Goods & Services

Providing in vitro fertilization genetic testing services for scientific research purposes; genetic testing of in vitro generated embryos for genetic diseases for research purposes; DNA screening of in vitro generated embryos for scientific research purposes; genetic testing of in vitro generated embryos for scientific research purposes; genetic testing for scientific research purposes in the field of human reproduction; prenatal testing for scientific research purposes; testing of in vitro generated embryos for fetal chromosomal abnormalities for research purposes; providing information in the fields of genetic testing of in vitro generated embryo, genetic testing, and prenatal testing of in vitro generated embryo for research purposes; providing a website featuring information about genetic testing of in vitro generated embryos and prenatal testing for scientific research purposes Providing in vitro fertilization genetic testing services for medical purposes; genetic testing for genetic disease carrier screening purposes of in vitro generated embryos for medical purposes; DNA screening of in vitro generated embryos for medical genetic testing purposes; genetic counseling; providing information in the fields of genetic carrier screening, genetic testing, and prenatal testing for medical purpose; providing a website featuring information about genetic testing of in vitro generated embryos, and prenatal testing of in vitro generated embryos for medical purposes

Abstract

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G06N 20/00 - Machine learning
• G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• C12Q 1/6869 - Methods for sequencing
• G16B 40/20 - Supervised data analysis
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16Z 99/00 - Subject matter not provided for in other main groups of this subclass
• G06N 7/01 - Probabilistic graphical models, e.g. probabilistic networks
• G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
• G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis

Abstract

The invention provides methods for preparing a preparation of amplified DNA derived from a biological sample of a patient who has been diagnosed with cancer useful for determining relapse or metastasis of cancer, comprising (a) sequencing DNA isolated from hematopoiesis cells in a blood or bone marrow sample of the patient or a fraction thereof to determine the presence or absence of one or more clonal hematopoiesis of indeterminate potential (CHIP) mutations; (b) sequencing (i) DNA isolated from a tumor biopsy sample of the patient or (ii) cell-free DNA isolated from the blood or bone marrow sample or a fraction thereof, to identify a plurality of patient-specific somatic mutations associated with the cancer; (c) preparing a preparation of amplified DNA by performing targeted multiplex amplification on cell-free DNA isolated from a longitudinally collected biological sample of the patient or a fraction thereof to amply a plurality of target loci to obtain amplified DNA, wherein each of the target loci spans a patient-specific somatic mutation identified in step (b) and does not span any CHIP mutation identified in step (a), wherein the biological sample is a blood, urine, or bone marrow sample; and (d) analyzing the preparation of amplified DNA by sequencing the amplified DNA to determine the presence or absence of the patient-specific somatic mutations, wherein the presence of two or more patient-specific somatic mutations associated with the cancer and the presence of one or more CHIP mutations are indicative of relapse or metastasis of the cancer.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

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.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids

Abstract

The present disclosure provides methods for quantifying the amount of total cell-free DNA in a biological sample, comprising: isolating cell-free DNA from the biological sample, wherein a first Tracer DNA composition is added before or after isolation of the cell-free DNA; performing targeted amplification at 100 or more different target loci in a single reaction volume using 100 or more different primer pairs; sequencing the amplification products by high-throughput sequencing to generate sequencing reads; and quantifying the amount of total cell-free DNA using sequencing reads derived from the first Tracer DNA composition.

IPC Classes  ?

• C12Q 1/6851 - Quantitative amplification
• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes

Abstract

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6869 - Methods for sequencing

Abstract

The present disclosure provides methods for preparing a preparation of amplified DNA derived from a blood sample of a pregnant woman useful for identifying pregnancies having high risks of preterm birth, preeclampsia, small for gestational age, spontaneous termination, and/or non-livebirth, comprising: (a) extracting cell-free DNA from the blood sample; (b) performing targeted multiplex amplification on the extracted DNA to amplify 200-20,000 SNP loci in a single reaction volume; and (c) performing high-throughput sequencing on the amplified DNA to obtain sequence reads and using the sequence reads to determine the ploidy state of the one or more chromosomes of interest; wherein a fetal fraction of less than 2.8% and/or no-call of the ploidy state of the one or more chromosomes of interest is indicative of pregnancies having high risks of preterm birth, preeclampsia, small for gestational age, spontaneous termination, and/or non-livebirth.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

The present disclosure provides methods for preparing a preparation of amplified DNA derived from a blood sample of a pregnant woman useful for identifying pregnancies having high risks of preterm birth, preeclampsia, small for gestational age, spontaneous termination, and/or non-livebirth, comprising: (a) extracting cell-free DNA from the blood sample; (b) performing targeted multiplex amplification on the extracted DNA to amplify 200-20,000 SNP loci in a single reaction volume; and (c) performing high-throughput sequencing on the amplified DNA to obtain sequence reads and using the sequence reads to determine the ploidy state of the one or more chromosomes of interest; wherein a fetal fraction of less than 2.8% and/or no-call of the ploidy state of the one or more chromosomes of interest is indicative of pregnancies having high risks of preterm birth, preeclampsia, small for gestational age, spontaneous termination, and/or non-livebirth.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

Disclosed here is a method for detecting genome rearrangement in a biological sample, comprising: obtaining a contact matrix plotted from proximity ligation sequencing data of at least one chromosome; identifying an abnormal contact pattern in the contact matrix compared to the contact matrix of a reference genome; comparing the abnormal contact pattern in the contact matrix to one or more known patterns associated with genomic rearrangement to identify a type of genomic rearrangement causing the abnormal contact pattern. Also disclosed is a method for detecting genome rearrangement in a biological sample, comprising: selecting linked chromosomal fragments from proximity ligation sequencing data of at least one chromosome, identifying an abnormal covalent bonding pattern of the linked chromosomal fragments compared to a reference genome; and comparing the abnormal covalent bonding pattern to one or more known patterns associated with genomic rearrangement to identify genomic rearrangement causing the abnormal covalent bonding pattern.

IPC Classes  ?

• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

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.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6862 - Ligase chain reaction [LCR]
• C12Q 1/686 - Polymerase chain reaction [PCR]
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Abstract

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G06N 20/00 - Machine learning
• G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• C12Q 1/6869 - Methods for sequencing
• G16B 40/20 - Supervised data analysis
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16Z 99/00 - Subject matter not provided for in other main groups of this subclass
• G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
• G06N 7/00 - Computing arrangements based on specific mathematical models
• G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis

Abstract

The invention provides methods for preparing a preparation of amplified DNA derived from a biological sample of a pregnant woman useful for identifying neoplasm in a pregnant woman, comprising: (a) isolating cell-free DNA from a biological sample of a pregnant woman comprising a mixture of fetal cell-free DNA and maternal cell-free DNA; (b) preparing a preparation of amplified DNA by performing targeted multiplex amplification on the isolated cell-free DNA to amplify at least 100 polymorphic loci; (c) analyzing the preparation of amplified DNA by sequencing the amplified DNA to obtain sequence reads of the at least 100 polymorphic loci and using the sequence reads to identify copy number variations (CNVs) in fetal and maternal chromosomes or chromosomal segments of interest, and identifying neoplasm in the pregnant woman by the presence of two or more of CNVs in the maternal chromosomes or chromosomal segments of interest.

IPC Classes  ?

• C12Q 1/6858 - Allele-specific amplification
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The invention provides methods for preparing a preparation of amplified DNA derived from a biological sample of a pregnant woman useful for identifying neoplasm in a pregnant woman, comprising: (a) isolating cell-free DNA from a biological sample of a pregnant woman comprising a mixture of fetal cell-free DNA and maternal cell-free DNA; (b) preparing a preparation of amplified DNA by performing targeted multiplex amplification on the isolated cell-free DNA to amplify at least 100 polymorphic loci; (c) analyzing the preparation of amplified DNA by sequencing the amplified DNA to obtain sequence reads of the at least 100 polymorphic loci and using the sequence reads to identify copy number variations (CNVs) in fetal and maternal chromosomes or chromosomal segments of interest, and identifying neoplasm in the pregnant woman by the presence of two or more of CNVs in the maternal chromosomes or chromosomal segments of interest.

IPC Classes  ?

• C12Q 1/6858 - Allele-specific amplification
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

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.

IPC Classes  ?

• C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
• C12Q 1/6853 - Nucleic acid amplification reactions using modified primers or templates
• C12Q 1/6858 - Allele-specific amplification
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/10 - Ploidy or copy number detection
• G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis

Abstract

The invention provides methods for determining the growth rate of ctDNA, comprising (a) sequencing nucleic acids isolated from a biological sample of a cancer patient to identify patient-specific cancer mutations; (b) quantify the amount of ctDNA in a first liquid biopsy sample collected from the cancer patient by performing a multiplex amplification reaction to amplify target loci from cfDNA isolated from the first liquid biopsy sample, wherein each target locus spans at least one patient-specific cancer mutation, and sequencing the amplified target loci to identify the patient-specific cancer mutations and quantify the amount of ctDNA in the first liquid biopsy sample; (c) quantify the amount of ctDNA in a second liquid biopsy sample collected from the cancer patient by performing a multiplex amplification reaction to amplify target loci from cfDNA isolated from the second liquid biopsy sample, wherein each target locus spans at least one patient-specific cancer mutation, and sequencing the amplified target loci to identify the patient-specific cancer mutations and quantify the amount of ctDNA in the second liquid biopsy sample; and (d) determining the growth rate of the ctDNA between the first and second liquid biopsy samples.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Goods & Services

Medical and scientific research and analysis in the field of genetic testing; providing medical and scientific research information in the field of genetic testing; medical laboratory services; genetic testing for scientific research and analysis purposes; genetic testing for scientific research and analysis purposes in the field of human reproduction; providing a website featuring information in the field of genetic testing for scientific purposes; providing a web-based patient portal featuring technology for accessing medical and healthcare information and genetic test results Genetic testing for medical purposes; genetic counseling; genetic testing for medical purposes and genetic counseling in the field of human reproduction; providing a website featuring information about genetic testing for medical purposes and genetic counseling

Abstract

The invention provides methods for determining the growth rate of ctDNA, comprising (a) sequencing nucleic acids isolated from a biological sample of a cancer patient to identify patient-specific cancer mutations; (b) quantify the amount of ctDNA in a first liquid biopsy sample collected from the cancer patient by performing a multiplex amplification reaction to amplify target loci from cfDNA isolated from the first liquid biopsy sample, wherein each target locus spans at least one patient-specific cancer mutation, and sequencing the amplified target loci to identify the patient-specific cancer mutations and quantify the amount of ctDNA in the first liquid biopsy sample; (c) quantify the amount of ctDNA in a second liquid biopsy sample collected from the cancer patient by performing a multiplex amplification reaction to amplify target loci from cfDNA isolated from the second liquid biopsy sample, wherein each target locus spans at least one patient-specific cancer mutation, and sequencing the amplified target loci to identify the patient-specific cancer mutations and quantify the amount of ctDNA in the second liquid biopsy sample; and (d) determining the growth rate of the ctDNA between the first and second liquid biopsy samples.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

The invention provides methods for determining the growth rate of ctDNA, comprising (a) sequencing nucleic acids isolated from a biological sample of a cancer patient to identify patient-specific cancer mutations; (b) quantify the amount of ctDNA in a first liquid biopsy sample collected from the cancer patient by performing a multiplex amplification reaction to amplify target loci from cfDNA isolated from the first liquid biopsy sample, wherein each target locus spans at least one patient-specific cancer mutation, and sequencing the amplified target loci to identify the patient-specific cancer mutations and quantify the amount of ctDNA in the first liquid biopsy sample; (c) quantify the amount of ctDNA in a second liquid biopsy sample collected from the cancer patient by performing a multiplex amplification reaction to amplify target loci from cfDNA isolated from the second liquid biopsy sample, wherein each target locus spans at least one patient-specific cancer mutation, and sequencing the amplified target loci to identify the patient-specific cancer mutations and quantify the amount of ctDNA in the second liquid biopsy sample; and (d) determining the growth rate of the ctDNA between the first and second liquid biopsy samples.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

This invention relates to methods and compositions for assessing the suitability of a graft for transplantation by measuring total and/or specific cell-free nucleic acids (such as cf-DNA) and/or cell lysis. Specifically, the method comprising obtaining an amount of total short fragment cf-DNA and/or graft-specific short fragment cf-DNA released from a potential graft (e.g., ex vivo), e.g., prior to contacting of the potential graft with blood cells of a potential recipient, and/or subsequent to contacting of the potential graft or cells thereof with blood cells from a potential recipient, and assessing the amount(s) to determine the suitability of the potential graft

IPC Classes  ?

• C12Q 1/6851 - Quantitative amplification

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Abstract

The present disclosure provides methods for preparation and analysis of biological samples of transplant recipients for determination of transplant rejection, comprising: (a) measuring the amount of Torque teno virus (TTV) in a blood, plasma, serum, or urine sample of a transplant recipient; (b) measuring the amount of donor-derived cell-free DNA in a blood, plasma, serum, or urine sample of the transplant recipient; and (c) determining whether the amount of donor-derived cell-free DNA or a function thereof exceeds a cutoff threshold indicating transplant rejection and whether the transplant recipient has an increased or decreased amount of TTV indicating decreased or increased immune response, respectively.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage

Abstract

Torque teno virusTorque teno virus (TTV) in a blood, plasma, serum, or urine sample of a transplant recipient; (b) measuring the amount of donor-derived cell-free DNA in a blood, plasma, serum, or urine sample of the transplant recipient; and (c) determining whether the amount of donor-derived cell-free DNA or a function thereof exceeds a cutoff threshold indicating transplant rejection and whether the transplant recipient has an increased or decreased amount of TTV indicating decreased or increased immune response, respectively.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage

Abstract

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G06N 20/00 - Machine learning
• G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• C12Q 1/6869 - Methods for sequencing
• G16B 40/20 - Supervised data analysis
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16Z 99/00 - Subject matter not provided for in other main groups of this subclass
• G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
• G06N 7/00 - Computing arrangements based on specific mathematical models
• G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
• G16B 25/20 - Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation

Abstract

The present disclosure provides methods of amplifying and sequencing DNA, comprising: extracting cell-free DNA from a blood, plasma, serum or urine sample of a transplant recipient who has received transplantation of one or more organs including simultaneous or sequential transplantation of multiple organs, wherein the extracted cell-free DNA comprises donor-derived cell-free DNA and recipient-derived cell-free DNA; performing targeted amplification at 200-50,000 target loci in a single reaction volume using 200-50,000 primer pairs, wherein the target loci comprise polymorphic loci and non-polymorphic loci; sequencing the amplification products by high-throughput sequencing to obtain a sequencing reads and quantifying the amount of donor-derived cell-free DNA and the amount of total cell-free DNA based on the sequencing reads; and determining whether the amount of donor-derived cell-free DNA or a function thereof exceeds a cutoff threshold indicating transplant rejection or graft injury.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6851 - Quantitative amplification

Abstract

The present disclosure provides methods of amplifying and sequencing DNA, comprising: extracting cell-free DNA from a blood, plasma, serum or urine sample of a transplant recipient who has received transplantation of one or more organs including simultaneous or sequential transplantation of multiple organs, wherein the extracted cell-free DNA comprises donor-derived cell-free DNA and recipient-derived cell-free DNA; performing targeted amplification at 200-50,000 target loci in a single reaction volume using 200-50,000 primer pairs, wherein the target loci comprise polymorphic loci and non-polymorphic loci; sequencing the amplification products by high-throughput sequencing to obtain a sequencing reads and quantifying the amount of donor-derived cell-free DNA and the amount of total cell-free DNA based on the sequencing reads; and determining whether the amount of donor-derived cell-free DNA or a function thereof exceeds a cutoff threshold indicating transplant rejection or graft injury.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6851 - Quantitative amplification

Abstract

The disclosure herein provides methods and compositions for detecting or monitoring immune cell populations in biological samples. The methods and compositions disclosed herein are particularly useful for detecting or monitoring immune cell populations in patients suffering from a disease or undergoing treatment of a disease resulting in depletion of immune cells. In particular, the present disclosure provides method for using multiplex PCR combined with next-generation DNA sequencing to detect DNA containing recombined V(D)J gene segments which can be used to detect immune cells.

IPC Classes  ?

• C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes

Abstract

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G06N 7/00 - Computing arrangements based on specific mathematical models
• G06N 20/00 - Machine learning
• G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 40/20 - Supervised data analysis
• G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
• G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
• G16Z 99/00 - Subject matter not provided for in other main groups of this subclass
• C12Q 1/6869 - Methods for sequencing

Abstract

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6869 - Methods for sequencing

Abstract

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• G06N 7/00 - Computing arrangements based on specific mathematical models
• G06N 20/00 - Machine learning
• G16B 15/00 - ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 40/20 - Supervised data analysis
• G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
• G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
• G16Z 99/00 - Subject matter not provided for in other main groups of this subclass
• C12Q 1/6869 - Methods for sequencing

Abstract

Provided herein are improved methods of determining the sequences of cell-free DNA (cfDNA). The methods in certain embodiments are used for the analysis of circulating DNA in serum samples, such as circulating fetal DNA, circulating donor derived DNA, or circulating tumor DNA. In certain embodiments, the methods include selectively enriching trinucleosomal, dinucleosomal, mononucleosomal or sub-mononucleosomal DNA from the isolated cfDNA.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/686 - Polymerase chain reaction [PCR]

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.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• G16B 20/10 - Ploidy or copy number detection
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12Q 1/6862 - Ligase chain reaction [LCR]
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

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.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/40 - Population genetics; Linkage disequilibrium
• G16B 20/10 - Ploidy or copy number detection
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12Q 1/6862 - Ligase chain reaction [LCR]
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

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.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/40 - Population genetics; Linkage disequilibrium
• G16B 20/10 - Ploidy or copy number detection
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12Q 1/6862 - Ligase chain reaction [LCR]
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

The invention provides methods for characterizing and analyzing circulating cells. In particular, the invention provides methods for confirming the identity of an individual cell and that the obtained sample was derived from a single cell of a defined identity. Additional methods are provided for analyzing single cell samples to determine copy number variation and aneuploidy in the context of circulating fetal cells, microdeletions, single nucleic acid variations associated with cancer, or early relapse of cancer and metastasis.

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/682 - Signal amplification
• C12Q 1/6869 - Methods for sequencing

Abstract

The invention provides methods for detecting single nucleotide variants in breast cancer, bladder cancer, or colorectal cancer. Additional methods and compositions, such as reaction mixtures and solid supports comprising clonal populations of nucleic acids, are provided. For example, provided here is a method for monitoring and detection of early relapse or metastasis of breast cancer, bladder cancer, or colorectal cancer, comprising generating a set of amplicons by performing a multiplex amplification reaction on nucleic acids isolated from a sample of blood or urine or a fraction thereof from a patient who has been treated for a breast cancer, bladder cancer, or colorectal cancer, wherein each amplicon of the set of amplicons spans at least one single nucleotide variant locus of a set of patient-specific single nucleotide variant loci associated with the breast cancer, bladder cancer, or colorectal cancer; and determining the sequence of at least a segment of each amplicon of the set of amplicons that comprises a patient-specific single nucleotide variant locus, wherein detection of one or more patient-specific single nucleotide variants is indicative of early relapse or metastasis of breast cancer, bladder cancer, or colorectal cancer.

IPC Classes  ?

• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/686 - Polymerase chain reaction [PCR]
• G16B 5/20 - Probabilistic models
• G16B 20/10 - Ploidy or copy number detection
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• G16B 30/10 - Sequence alignment; Homology search
• C12Q 1/6869 - Methods for sequencing
• G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment

Abstract

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6869 - Methods for sequencing

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Abstract

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.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6869 - Methods for sequencing

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.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• G16B 20/40 - Population genetics; Linkage disequilibrium
• G16B 20/10 - Ploidy or copy number detection
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12Q 1/6862 - Ligase chain reaction [LCR]
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding

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.

IPC Classes  ?

• G16B 20/10 - Ploidy or copy number detection
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 5/20 - Probabilistic models

Abstract

The present disclosure provides methods for quantifying the amount of total cell-free DNA in a biological sample, comprising: isolating cell-free DNA from the biological sample, wherein a first Tracer DNA composition is added before or after isolation of the cell-free DNA; performing targeted amplification at 100 or more different target loci in a single reaction volume using 100 or more different primer pairs; sequencing the amplification products by high-throughput sequencing to generate sequencing reads; and quantifying the amount of total cell-free DNA using sequencing reads derived from the first Tracer DNA composition.

IPC Classes  ?

• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

The present disclosure provides methods for quantifying the amount of total cell-free DNA in a biological sample, comprising: isolating cell-free DNA from the biological sample, wherein a first Tracer DNA composition is added before or after isolation of the cell-free DNA; performing targeted amplification at 100 or more different target loci in a single reaction volume using 100 or more different primer pairs; sequencing the amplification products by high-throughput sequencing to generate sequencing reads; and quantifying the amount of total cell-free DNA using sequencing reads derived from the first Tracer DNA composition.

IPC Classes  ?

• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

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.

IPC Classes  ?

• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

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.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing
• G16B 10/00 - ICT specially adapted for evolutionary bioinformatics, e.g. phylogenetic tree construction or analysis
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• C12Q 1/6844 - Nucleic acid amplification reactions

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.

IPC Classes  ?

• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• C12Q 1/6869 - Methods for sequencing
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations

Abstract

This invention relates to methods and compositions for assessing the suitability of a graft for transplantation or implantation by measuring total and/or specific cell-free nucleic acids (such as cf-DNA) and/or cell lysis. Specifically, the method comprising obtaining an amount of total cf DNA and/or graft-specific cfDNA released from a potential graft (e.g., ex vivo), e.g., prior to contacting of the potential graft with blood cells of a potential recipient, and/or subsequent to contacting of the potential graft or cells thereof with blood cells from a potential recipient, assessing the amount(s) to determine the suitability of the potential graft for transplantation or implantation.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

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.

IPC Classes  ?

• G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

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.

IPC Classes  ?

• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids

Abstract

The present disclosure provides methods for determining the status of an allograft within a transplant recipient from genotypic data measured from a mixed sample of DNA comprising DNA from both the transplant recipient and from the donor. 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.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• C12Q 1/6851 - Quantitative amplification

Abstract

The present disclosure provides methods for determining the status of an allograft within a transplant recipient from genotypic data measured from a mixed sample of DNA comprising DNA from both the transplant recipient and from the donor. 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.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• C12Q 1/6851 - Quantitative amplification

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

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.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction

Abstract

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6869 - Methods for sequencing

Abstract

This invention relates to methods and compositions for assessing the suitability of a graft for transplantation by measuring total and/or specific cell-free nucleic acids (such as cf-DNA) and/or cell lysis. Specifically, the method comprising obtaining an amount of total short fragment cf-DNA and/or graft-specific short fragment cf-DNA released from a potential graft (e.g., ex vivo), e.g., prior to contacting of the potential graft with blood cells of a potential recipient, and/or subsequent to contacting of the potential graft or cells thereof with blood cells from a potential recipient, and assessing the amount(s) to determine the suitability of the potential graft for transplantation.

IPC Classes  ?

• C12Q 1/686 - Polymerase chain reaction [PCR]

Abstract

Disclosed here is a composition comprising a primer that is (a) a loopable primer comprising a target-specific section, an adaptor section, and a stem-forming section, wherein the stem-forming section is hybridizable to a portion of the target-specific section to form a stem structure, or (b) a split primer comprising a first target-specific section, a second target-specific section, and an adaptor section positioned between the first target-specific section and the second target-specific section, or (c) a split-loopable primer comprising a first target-specific section, a second target-specific section, a stem-forming section positioned between the first target-specific section and the second target-specific section, and an adaptor section, or comprising a first adaptor section, a second adaptor section, a stem-forming section positioned between the first adaptor section and the second adaptor section, and a target-specific section. Also disclosed is a method for amplifying a target locus of interest from a template DNA, comprising at least two pre-amplification cycles using the loopable primer, the split primer and/or the split-loopable primer, wherein each amplification cycle comprises annealing the primer to the template DNA or pre-amplification product thereof and elongating the annealed primer. Further disclosed is a kit for amplifying a target locus of interest, comprising the loopable primer, the split primer, and/or the split-loopable primer.

IPC Classes  ?

• C12Q 1/6853 - Nucleic acid amplification reactions using modified primers or templates
• C12Q 1/6858 - Allele-specific amplification

Abstract

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12Q 1/6869 - Methods for sequencing

Goods & Services

(1) Reagents for medical use in the fields of oncology and tumor identification, analysis, and treatment; medical diagnostic reagents for use in the fields of oncology and tumor identification, analysis, and treatment; genetic tests comprised of reagents for medical purposes in the fields of oncology and tumor identification, analysis, and treatment. (2) Blood collection kit comprised of blood collecting tubes for use in the fields of oncology and tumor identification, analysis, and treatment; tissue collection kit comprised of tissue collecting containers and refrigerants, for use in the fields of oncology and tumor identification, analysis, and treatment. (1) Genetic testing and sequencing for scientific research and analysis purposes; genetic testing and sequencing for scientific research and analysis purposes in the fields of oncology and tumor identification, analysis, and treatment. (2) Genetic testing and sequencing for medical, diagnostic, and treatment purposes; genetic testing and sequencing for medical, diagnostic, and treatment purposes in the fields of oncology and tumor identification, analysis, and treatment.

Goods & Services

Reagents for medical use in the fields of oncology and tumor identification, analysis, and treatment; medical diagnostic reagents for use in the fields of oncology and tumor identification, analysis, and treatment; genetic tests comprised of reagents for medical purposes in the fields of oncology and tumor identification, analysis, and treatment. Blood collection kit comprised of blood collecting tubes for use in the fields of oncology and tumor identification, analysis, and treatment; tissue collection kit comprised of tissue collecting containers and refrigerants, for use in the fields of oncology and tumor identification, analysis, and treatment. Genetic testing and sequencing for scientific research and analysis purposes; genetic testing and sequencing for scientific research and analysis purposes in the fields of oncology and tumor identification, analysis, and treatment. Genetic testing and sequencing for medical, diagnostic, and treatment purposes; genetic testing and sequencing for medical, diagnostic, and treatment purposes in the fields of oncology and tumor identification, analysis, and treatment.

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.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection

Abstract

Disclosed here is a method for isolating nucleic acids from a biological sample, comprising: (a) contacting a first composition comprising nucleic acids obtained from a biological sample with a first matrix under a low-stringency binding condition having less than 1% aliphatic alcohols that binds less than 5% of nucleic acids of shorter than about 118 bp and more than 30% of nucleic acids longer than about 194 bp to a first matrix; and (b) contacting a second composition comprising remainder of the first composition with a second matrix under a high-stringency binding condition having less than 1% aliphatic alcohol that binds more than 70% of nucleic acids longer than about 72 bp and 30% of nucleic acids longer than about 50 bp to the second matrix. Further disclosed is a kit for isolating nucleic acids from a biological sample, comprising (a) a first binding buffer for establishing a low-stringency binding condition having less than 1% aliphatic alcohols that binds less than 5% of nucleic acids shorter than about 118 bp and more than 30% of nucleic acids longer than about 194 bp to a matrix, and (b) a second binding buffer for establishing a high-stringency binding condition having less than 1% aliphatic alcohol that binds more than 70% of nucleic acids longer than about 72 bp and 30% of nucleic acids longer than about 50 bp to the matrix.

IPC Classes  ?

• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12Q 1/6853 - Nucleic acid amplification reactions using modified primers or templates

Abstract

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.

IPC Classes  ?

• C12Q 1/6869 - Methods for sequencing
• G16B 10/00 - ICT specially adapted for evolutionary bioinformatics, e.g. phylogenetic tree construction or analysis
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes

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.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

Abstract

The disclosure herein provides methods and compositions for detecting or monitoring immune cell populations in biological samples. The methods and compositions disclosed herein are particularly useful for detecting or monitoring immune cell populations in patients suffering from a disease or undergoing treatment of a disease resulting in depletion of immune cells. In particular, the present disclosure provides method for using multiplex PCR combined with next-generation DNA sequencing to detect DNA containing recombined V(D)J gene segments which can be used to detect immune cells.

IPC Classes  ?

• C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer

Abstract

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes

Abstract

Provided herein are methods for determining the ploidy state of one or more chromosome in a developing fetus. The subject methods provide for increase accuracy by utilizing information about the mosaicism level of one or more chromosomes of interest in the mother of fetus. The mosaicism level of one or more chromosomes of interest is determine for the maternal tissue that is used as the source of nucleic acid for genetic analysis that are used to determine the ploidy state of the fetal chromosome or chromosomes of interest. For example, if 5% white blood cells of mother are missing a copy of the X chromosome, this information can be used when determining fetal ploidy level, rather than operating under the assumption that the maternal X chromosome are present in two copies. Utilization of the mosaicism data can be used to increase the reliability and accuracy of the determination of the ploidy state of a chromosome of interest.

IPC Classes  ?

• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material

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.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6869 - Methods for sequencing
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Abstract

Provided herein are improved methods of determining the sequences of cell-free DNA (cfDNA). The methods in certain embodiments are used for the analysis of circulating DNA in serum samples, such as circulating fetal DNA, circulating donor derived DNA, or circulating tumor DNA. In certain embodiments, the methods include selectively enriching trinucleosomal, dinucleosomal, mononucleosomal or sub-mononucleosomal DNA from the isolated cfDNA.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism

Abstract

Provided herein are improved methods of determining the sequences of cell-free DNA (cfDNA). The methods in certain embodiments are used for the analysis of circulating DNA in serum samples, such as circulating fetal DNA, circulating donor derived DNA, or circulating tumor DNA. In certain embodiments, the methods include selectively enriching trinucleosomal, dinucleosomal, mononucleosomal or sub-mononucleosomal DNA from the isolated cfDNA.

IPC Classes  ?

• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Goods & Services

Reagents for medical use in the fields of oncology and tumor identification, analysis, and treatment; medical diagnostic reagents for use in the fields of oncology and tumor identification, analysis, and treatment; genetic tests comprised of reagents for medical purposes in the fields of oncology and tumor identification, analysis, and treatment Blood collection kit comprised of blood collecting tubes for use in the fields of oncology and tumor identification, analysis, and treatment; tissue collection kit comprised of tissue collecting containers, for use in the fields of oncology and tumor identification, analysis, and treatment Genetic testing and sequencing for scientific research and analysis purposes; genetic testing and sequencing for scientific research and analysis purposes in the fields of oncology and tumor identification, analysis, and treatment Genetic testing and sequencing for medical, diagnostic, and treatment purposes; genetic testing and sequencing for medical, diagnostic, and treatment purposes in the fields of oncology and tumor identification, analysis, and treatment

Abstract

The invention relates to subject-specific methods for detecting recurrence of tumours based on an understanding of the clonal/subclonal mutation profile of the subject's tumour and detection of the mutations in their cell-free DNA (cfDNA), typically by multiplex PCR of tumour mutations such as single nucleotide variants (SNVs).

IPC Classes  ?

• C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
• C12Q 1/686 - Polymerase chain reaction [PCR]

Abstract

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.

IPC Classes  ?

• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations

Abstract

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.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
• G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
• G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
• C12Q 1/6869 - Methods for sequencing

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.

IPC Classes  ?

• C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
• C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
• C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
• C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
• C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
• C12Q 1/6851 - Quantitative amplification
• C12Q 1/6844 - Nucleic acid amplification reactions
• C12Q 1/6855 - Ligating adaptors
• C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]

Goods & Services

(1) Blood collection kit comprised of blood collecting tubes; saliva collection kit comprised of saliva collecting tubes (1) Medical and scientific research and analysis in the field of genetic testing; providing medical and scientific research information in the field of genetic testing; medical laboratory services; genetic testing for scientific research and analysis purposes; providing a website featuring information in the field of genetic testing for scientific purposes (2) Genetic testing for medical purposes; genetic counseling; providing a website featuring information about genetic testing for medical purposes and genetic counseling