Technology provided herein relates in part to non-invasive classification of one or more genetic copy number variations (CNVs) for a test sample. Technology provided herein is useful for classifying a genetic CNV for a sample as part of non-invasive pre-natal (NIPT) testing and oncology testing, for example.
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
3.
Methods, Systems, and Compositions for the Analysis of Cell-Free Nucleic Acids
The present disclosure relates to methods for enriching circulating tumor DNA (ctDNA) to enhance early disease detection or predictions of disease progression. The present disclosure also relates to methods for enriching circulating fetal cell free DNA (fetal cfDNA) to enhance early disease detection. In some embodiments, the method comprises enriching ctDNA or fetal cfDNA in a sample by selecting for cell-free nucleic acid fragments that are less than 150 bp prior to copy number alteration (CNA) analysis. Also disclosed are compositions, systems, and computer-program products for analyzing circulating cell free nucleic acids by any of the methods disclosed herein.
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
4.
Methods for Non-Invasive Assessment of Genomic Instability
Technology provided herein relates in part to methods, processes, machines and apparatuses for non-invasive assessment of genomic nucleic acid instability and genomic nucleic acid stability.
Technology provided herein relates in part to methods, processes, machines and apparatuses for determining sequences of nucleotides for nucleic acid templates in a nucleic acid sample. The technology provide herein also relates in part to methods, processes, machines and apparatuses for counting nucleic acid templates. Nucleic acid templates of a sample are tagged with nonrandom oligonucleotide adapters that include predetermined non-randomly generated sequences. The use of these nonrandom oligonucleotide adapters provides an efficient method to reduce sequencing errors, and increase the sensitivity of detection of low-frequency single nucleotide alterations.
C12Q 1/683 - Hybridisation assays for detection of mutation or polymorphism involving restriction enzymes, e.g. restriction fragment length polymorphism [RFLP]
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
Provided are compositions and processes that utilize genomic regions that are differentially methylated between a mother and her fetus to separate, isolate or enrich fetal nucleic acid from a maternal sample. The compositions and processes described herein are particularly useful for non-invasive prenatal diagnostics, including the detection of chromosomal aneuploidies.
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
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
9.
Methods and Processes for Non-Invasive Assessment of Genetic Variations
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 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
G16B 45/00 - ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks
G16B 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation
G16B 25/20 - Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation
10.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF GENETIC VARIATIONS
Provided herein are methods, processes and apparatuses for non-invasive assessment of genetic variations that make use of decision analyses. The decision analyses sometimes include segmentation analyses and/or odds ratio analyses.
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 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation
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
12.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF GENETIC VARIATIONS
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
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 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G16B 20/40 - 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
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C12Q 1/6804 - Nucleic acid analysis using immunogens
14.
METHODS AND COMPOSITIONS FOR ANALYZING NUCLEIC ACID
Provided are methods for identifying the presence or absence of a chromosome abnormality by which a cell-free sample nucleic acid from a subject is analyzed. In certain embodiments, provided are methods for identifying the presence or absence of a fetal chromosome abnormality in a nucleic acid from cell-free maternal blood.
G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
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
G16B 25/20 - Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation
16.
COMPOSITIONS, METHODS, AND SYSTEMS TO DETECT HEMATOPOIETIC STEM CELL TRANSPLANTATION STATUS
This application provides methods and systems for determining transplant status. In some embodiments, the method comprises obtaining a biological sample from hematopoietic stem cell transplant (HSCT) recipient; measuring the amount of one or more identified recipient-specific nucleic acids or donor-specific nucleic acids in the sample; and (c) determining transplant status by monitoring the amount of the one or more identified recipient-specific nucleic acids or donor-specific nucleic acids after transplantation. In some approaches, the one or more recipient-specific or the donor-specific nucleic acids are identified based on the amount of one or more polymorphic nucleic acid targets, which can be used to determine the transplant status. Optionally, the biological sample is blood or bone marrow. Optionally the nucleic acid is genomic DNA.
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
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
Technology provided herein relates in part to non-invasive classification of one or more genetic copy number alterations (CNAs) for a test sample. Certain methods include sampling a quantification of sequence reads from parts of a genome, generating a confidence determination, and using the confidence determination to enhance classification. Technology provided herein is useful for classifying a genetic CNA for a sample as part of non-invasive pre-natal (NIPT) testing and oncology testing, for example.
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 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
G06N 7/00 - Computing arrangements based on specific mathematical models
The present invention relates to an in vitro method for detecting methylated DNA comprising (a) coating a container with a polypeptide capable of binding methylated DNA; (b) contacting said polypeptide with a sample comprising methylated and/or unmethylated DNA; and (c) detecting the binding of said polypeptide to methylated DNA. In a preferred embodiment, said method further comprises step (d) analyzing the detected methylated DNA by sequencing. Another aspect of the present invention is a kit for detecting methylated DNA according to the methods of the invention comprising (a) a polypeptide capable of binding methylated DNA; (b) a container which can be coated with said polypeptide; (c) means for coating said container; and (d) means for detecting methylated DNA.
C12Q 1/6804 - Nucleic acid analysis using immunogens
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
19.
Methods and processes for assessment of genetic variations
Technology provided herein relates in part to non-invasive classification of one or more genetic copy number variations (CNVs) for a test sample. Technology provided herein is useful for classifying a genetic CNV for a sample as part of non-invasive pre-natal (NIPT) testing and oncology testing, for example.
The present application relates to a nucleic acid molecule having a nucleotide sequence encoding a bifunctional polypeptide comprising the DNA-binding domain of a protein belonging to the family of Methyl-CpG binding proteins (MBDs) and the Fc portion of an antibody. In addition, vectors and host cells which comprise said nucleic acid molecule and polypeptides which are encoded by said nucleic acid molecule as well as processes for producing said polypeptide are disclosed. Moreover, the present application provides an antibody specifically binding said polypeptide and compositions, in particular diagnostic compositions comprising the nucleic acid molecule(s), vector(s), host cell(s), polypeptide(s) or antibodie(s) of the present application. Furthermore, methods and uses employing the polypeptides of the present invention for detecting methylated DNA, in particular in tumorous tissue or tumor cells are provided.
H04N 21/24 - Monitoring of processes or resources, e.g. monitoring of server load, available bandwidth or upstream requests
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
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
21.
METHODS, AND SYSTEMS TO DETECT TRANSPLANT REJECTION
This application provides methods and systems for determining transplant status. In some embodiments, the method comprises obtaining a biological sample from an organ transplant recipient who has received an organ; isolating cell-free nucleic acids from the biological sample; measuring the amount of each allele of one or more polymorphic nucleic acid targets in the biological sample; identifying the donor specific allele using a computer algorithm based on the measurements of the one or more polymorphic nucleic acid targets, whereby detecting one or more donor-specific circulating cell-free nucleic acids, detecting tissue injury based on the presence or amount of said one or more donor-specific nucleic acids, thereby determining transplant status.
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
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] 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
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
G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
22.
METHODS FOR REDUCING GUANINE AND CYTOSINE (GC) BIAS IN NUCLEOTIDE SEQUENCE READ COUNTS
The invention generally relates to methods for analyzing nucleic acid sequence information. In some aspects, a sample is sequenced to obtain nucleic acid sequence information. In some aspects, an amount of GC bias in sequence information is determined. In some aspects, sequence information is corrected to account for the GC bias. In some aspects, corrected sequence information is analyzed.
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
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
Provided herein are methods, processes and apparatuses for non-invasive assessment of genetic variations that make use of nucleic acid fragments from circulating cell free nucleic acid. Also provided herein are methods for partitioning one or more genomic regions of a reference genome into a plurality of portions according to one or more features.
Blood plasma of pregnant women contains fetal and (generally >90%) maternal circulatory extracellular DNA. Most of said fetal DNA contains 500 base pairs, said maternal DNA having a greater size. Separation of circulatory extracellular DNA of <500 base pairs results in separation of fetal from maternal DNA. A fraction of a blood plasma or serum sample of a pregnant woman containing, due to size separation (e.g. by chromatography, density gradient centrifugation or nanotechnological methods), extracellular DNA substantially comprising 500 base pairs is useful for non-invasive detection of fetal genetic traits (including the fetal RhD gene in pregnancies at risk for HDN; fetal Y chromosome-specific sequences in pregnancies at risk for X chromosome-linked disorders; chromosomal aberrations; hereditary Mendelian genetic disorders and corresponding genetic markers; and traits decisive for paternity determination) by e.g. PCR, ligand chain reaction or probe hybridization techniques, or nucleic acid arrays.
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 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
25.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF GENETIC VARIATIONS
Provided in part herein are methods and processes that can be used for non-invasive assessment of a genetic variation which can lead to diagnosis of a particular medical condition or conditions. Such methods and processes can, for example, identify dissimiliarities or similarities for one or more features between a subject data set and a reference data set, generate a multidimensional matrix, reduce the matrix into a representation and classify the representation into one or more groups. Methods and processes described herein are applicable to data in biotechnology and other fields.
A method and system for analyzing circulating cell-free nucleic acids from a pregnant female with reduced bias. Counts of sequence reads mapped to portions of a reference genome are obtained. A regression model is generated that models the relationship between the counts and the GC content. The read counts are normalized according to the regression model to remove the GC bias. The normalized counts are used for further analysis, such as the detection of fetal aneuploidy.
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
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
G06F 17/18 - Complex mathematical operations for evaluating statistical data
Provided herein are methods and compositions to extract and enrich by, physical separation or amplification, relatively short nucleic acids from a nucleic acid composition containing a high background of longer nucleic acids (e.g., host or maternal nucleic acids; genomic nucleic acid and the like).
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
Improved solid supports and methods for analyzing target nucleotide sequences are provided herein. Certain improvements are directed to efficiently preparing nucleic acids that comprise nucleotide sequences identical to or substantially identical to one or more target nucleotide sequences, or complement thereof. The prepared nucleic acids include a reference sequence that facilitates sequence analysis. The solid supports and methods provided herein minimize the number of steps required by published sequence analysis methodologies, and thereby offer improved sequence analysis efficiency.
Provided are compositions and processes that utilize genomic regions differentially methylated between a mother and her fetus to separate, isolate or enrich fetal nucleic acid from a maternal sample. The compositions and processes described herein are useful for non-invasive prenatal diagnostics, including the detection of chromosomal aneuploidies.
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 1/6804 - Nucleic acid analysis using immunogens
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6879 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for sex determination
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
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C12Q 1/6804 - Nucleic acid analysis using immunogens
33.
Methods and compositions for the extraction and amplification of nucleic acid from a sample
Provided herein are methods, compositions and kits to extract and relatively enrich by physical separation or amplification short base pair nucleic acid in the presence of a high background of genomic material (e.g., host or maternal nucleic acids).
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
35.
Methods and processes for non-invasive assessment of genetic variations
Provided herein are methods, processes and apparatuses for non-invasive assessment of genetic variations that make use of decision analyses. The decision analyses sometimes include segmentation analyses and/or odds ratio analyses.
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
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 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation
36.
Processes and Compositions for Methylation-Based Enrichment of Fetal Nucleic Acid From a Maternal Sample Useful for Non-Invasive Prenatal Diagnoses
Provided are compositions and processes that utilize genomic regions that are differentially methylated between a mother and her fetus to separate, isolate or enrich fetal nucleic acid from a maternal sample. The compositions and processes described herein are particularly useful for non-invasive prenatal diagnostics, including the detection of chromosomal aneuploidies.
Technology provided herein relates in part to non-invasive classification of one or more mosaic copy number variations (CNVs) for a test sample. Technology provided herein is useful for classifying a mosaic CNV for a sample as part of non-invasive pre-natal (NIPT) testing and oncology testing, for example. In particular, a method is provided for classifying presence or absence of genetic mosaicism for a biological sample, the method includes identifying a genetic copy number variation region in sample nucleic acid from a subject, e.g. a pregnant female, determining a fraction of nucleic acid having the copy number variation in the sample nucleic acid, determining a fraction of a minority nucleic acid, e.g. fetal nucleic acid, in the sample nucleic acid, comparing the two fractions to generate a mosaicism ratio, and classifying a presence or absence of a genetic mosaicism for the copy number variation region according to the mosaicism ratio.
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
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
Technology provided herein relates in part to methods, processes, machines and apparatuses for determining sequences of nucleotides for nucleic acid templates in a nucleic acid sample. The technology provide herein also relates in part to methods, processes, machines and apparatuses for counting nucleic acid templates. Nucleic acid templates of a sample are tagged with nonrandom oligonucleotide adapters that include predetermined non-randomly generated sequences. The use of these nonrandom oligonucleotide adapters provides an efficient method to reduce sequencing errors, and increase the sensitivity of detection of low-frequency single nucleotide alterations.
Technology provided herein relates in part to methods, processes, machines and apparatuses for non-invasive assessment of copy number alterations. In particular, a method is provided for determining presence or absence of a copy number alteration for a test subject. The method includes providing a set of sequence reads. The sequence reads may be obtained from circulating cell free sample nucleic acid from a test sample obtained from the test subject, and the circulating cell free sample nucleic acid may be captured by probe oligonucleotides under hybridization conditions. The method further includes determining a probe coverage quantification of the sequence reads for the probe oligonucleotides and determining the presence or absence of a copy number alteration in the circulating cell free sample nucleic acid based on the probe coverage quantification of the sequence reads for the probe oligonucleotides for the test sample.
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
45.
Methods for non-invasive assessment of genetic alterations
Technology provided herein relates in part to methods, processes, machines and apparatuses for non-invasive assessment of genetic alterations. In particular, a method is provided for that includes obtaining a set of sequence reads. The sequence reads each include a single molecule barcode (SMB) sequence that is a non-random oligonucleotide sequence. The method further includes assigning the sequence reads to read groups according to a read group signature. The read group signature comprises an SMB sequence and a start and end position of a nucleic acid fragment from the circulating cell free sample nucleic acid. The sequence reads comprising start and end positions and an SMB sequence similar to the read group signature are assigned to a read group. The method further includes generating a consensus for each read group, and determining the presence or absence of a genetic alteration based on the consensus for each read group.
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
47.
Methods and processes for non-invasive assessment of genetic variations
Provided herein are methods for determining fetal ploidy according to nucleic acid sequence reads. Nucleic acid sequence reads may be obtained from test sample nucleic acid comprising circulating cell-free nucleic acid from the blood of a pregnant female bearing a fetus. Fetal ploidy may be determined according to genomic section levels and a fraction of fetal nucleic acid in a test sample.
C12Q 1/683 - Hybridisation assays for detection of mutation or polymorphism involving restriction enzymes, e.g. restriction fragment length polymorphism [RFLP]
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 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
Provided herein are methods and compositions to extract and enrich by, physical separation or amplification, relatively short nucleic acids from a nucleic acid composition containing a high background of longer nucleic acids (e.g., host or maternal nucleic acids; genomic nucleic acid and the like).
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
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 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G16B 20/40 - Population genetics; Linkage disequilibrium
Systems and methods for identifying a de novo mutation in a genome of a fetus are provided. Methods may include identifying a location of each of a plurality of cell-free nucleic acid molecules using sequence reads. Methods may also include identifying a first sequence in the sequence reads at a first location that is not present in the maternal or paternal sequences. Methods may additionally include determining a first fractional concentration of the first sequence in the biological sample at the first location. Further, methods may include determining a second fractional concentration of a fetal-specific second sequence. The second sequence may be inherited by the fetus from the father at the second location. In addition, methods may include classifying the first sequence as a de novo mutation at the first location in a fetal genome of the fetus if the first and second fractional concentrations are about the same.
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
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
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 1/6827 - Hybridisation assays for detection of mutation or polymorphism
Provided are methods for identifying the presence or absence of a chromosome abnormality by which a cell-free sample nucleic acid from a subject is analyzed. In certain embodiments, provided are methods for identifying the presence or absence of a fetal chromosome abnormality in a nucleic acid from cell-free maternal blood.
G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
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
G16B 25/20 - Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation
52.
Methods and compositions for analyzing nucleic acid
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 40/10 - Signal processing, e.g. from mass spectrometry [MS] or from PCR
Provided herein are methods and compositions to extract and enrich by, physical separation or amplification, relatively short nucleic acids from a nucleic acid composition containing a high background of longer nucleic acids (e.g., host or maternal nucleic acids; genomic nucleic acid and the like).
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 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
Technology provided herein relates in part to non-invasive classification of one or more genetic copy number alterations (CNAs) for a test sample. Certain methods include sampling a quantification of sequence reads from parts of a genome, generating a confidence determination, and using the confidence determination to enhance classification. Technology provided herein is useful for classifying a genetic CNA for a sample as part of non-invasive pre-natal (NIPT) testing and oncology testing, for example.
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 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
G06N 7/00 - Computing arrangements based on specific mathematical models
56.
Copy number alteration and reference genome mapping
Technology provided herein relates in part to methods, processes, machines and apparatuses for non-invasive assessment of genomic nucleic acid instability and genomic nucleic acid stability. The method comprises providing a set of genomic portions each coupled to a copy number alteration quantification for a test sample, wherein the genomic portions comprises portions of a reference genome to which sequence reads obtained for nucleic acid from a test sample obtained from the subject have been mapped, and the copy number alteration quantification coupled to each genomic portion has been determined from a quantification of sequence reads mapped to the genomic portion; and determining, by a computing device, presence or absence of genomic instability for the subject according to the copy number alteration quantifications coupled to the genomic portions.
Provided in part herein are methods and processes that can be used for non-invasive assessment of a genetic variation which can lead to diagnosis of a particular medical condition or conditions. Such methods and processes can, for example, identify dissimilarities or similarities for one or more features between a subject data set and a reference data set, generate a multidimensional matrix, reduce the matrix into a representation and classify the representation into one or more groups. Methods and processes described herein are applicable to data in biotechnology and other fields.
G16H 20/00 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
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
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 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
58.
Methods and processes for non-invasive assessment of genetic variations
Methods for non-invasive assessment of genetic variations that make use of nucleic acid fragment length information, in particular length of fragments in circulating cell-free nucleic acids and compares the number of counts from fragments with different length.
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
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 20/00 - 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
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
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C12Q 1/6804 - Nucleic acid analysis using immunogens
60.
Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
Provided are compositions and processes that utilize genomic regions that are differentially methylated between a mother and her fetus to separate, isolate or enrich fetal nucleic acid from a maternal sample. The compositions and processes described herein are particularly useful for non-invasive prenatal diagnostics, including the detection of chromosomal aneuploidies.
Provided herein are methods, processes and apparatuses for non-invasive assessment of genetic variations that make use of nucleic acid fragments from circulating cell free nucleic acid. Also provided herein are methods for partitioning one or more genomic regions of a reference genome into a plurality of portions according to one or more features.
Provided herein are methods and compositions to extract and enrich by, physical separation or amplification, relatively short nucleic acids from a nucleic acid composition containing a high background of longer nucleic acids (e.g., host or maternal nucleic acids; genomic nucleic acid and the like).
Technology provided herein relates in part to methods, processes and apparatuses for non-invasive assessment of genetic variations. In particular the invention relates to methods and kits for detecting aneuploidy of a fetal chromosome by determining the amounts of differentially methylated regions in each of chromosomes 13, 18 and 21 in circulating cell-free nucleic acid from a human pregnant female.
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 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
G16B 45/00 - ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks
G16B 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation
G16B 25/20 - Polymerase chain reaction [PCR]; Primer or probe design; Probe optimisation
H01J 49/16 - Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
64.
Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
Provided are compositions and processes that utilize genomic regions that are differentially methylated between a mother and her fetus to separate, isolate or enrich fetal nucleic acid from a maternal sample. The compositions and processes described herein are particularly useful for non-invasive prenatal diagnostics, including the detection of chromosomal aneuploidies.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
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
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
65.
Methods and compositions for the extraction and amplification of nucleic acid from a sample
Provided herein are methods, compositions and kits to extract and relatively enrich by physical separation or amplification short base pair nucleic acid in the presence of a high background of genomic material (e.g., host or maternal nucleic acids).
C12N 15/00 - Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
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
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
67.
Non-invasive assessment of chromosome alterations using change in subsequence mappability
Provided herein are methods, processes and apparatuses for non-invasive assessment of genetic variations that make use of decision analyses. The decision analyses sometimes include segmentation analyses and/or odds ratio analyses.
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
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
The present invention relates to an in vitro method for detecting methylated DNA comprising (a) coating a container with a polypeptide capable of binding methylated DNA; (b) contacting said polypeptide with a sample comprising methylated and/or unmethylated DNA; and (c) detecting the binding of said polypeptide to methylated DNA. In a preferred embodiment, said method further comprises step (d) analyzing the detected methylated DNA by sequencing. Another aspect of the present invention is a kit for detecting methylated DNA according to the methods of the invention comprising (a) a polypeptide capable of binding methylated DNA; (b) a container which can be coated with said polypeptide; (c) means for coating said container; and (d) means for detecting methylated DNA.
C12Q 1/6804 - Nucleic acid analysis using immunogens
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 1/6883 - 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
71.
Methods and processes for non-invasive assessment of genetic variations
A method and system for analyzing circulating cell-free nucleic acids from a pregnant female with reduced bias, Counts of sequence reads mapped to portions of a reference genome are obtained. A regression model is generated that models the relationship between the counts and the GC content. The read counts are normalized according to the regression model to remove the GC bias. The normalized counts are used for further analysis, such as the detection of fetal aneuploidy.
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
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
G06F 17/18 - Complex mathematical operations for evaluating statistical data
72.
Compositions containing identifier sequences on solid supports for nucleic acid sequence analysis
Improved solid supports and methods for analyzing target nucleotide sequences are provided herein. Certain improvements are directed to efficiently preparing nucleic acids that comprise nucleotide sequences identical to or substantially identical to one or more target nucleotide sequences, or complement thereof. The prepared nucleic acids include a reference sequence that facilitates sequence analysis. The solid supports and methods provided herein minimize the number of steps required by published sequence analysis methodologies, and thereby offer improved sequence analysis efficiency.
Improved solid supports and methods for analyzing target nucleotide sequences are provided herein. Certain improvements are directed to efficiently preparing nucleic acids that comprise nucleotide sequences identical to or substantially identical to one or more target nucleotide sequences, or complement thereof. The prepared nucleic acids include a reference sequence that facilitates sequence analysis. The solid supports and methods provided herein minimize the number of steps required by published sequence analysis methodologies, and thereby offer improved sequence analysis efficiency.
Provided are compositions and processes that utilize genomic regions differentially methylated between a mother and her fetus to separate, isolate or enrich fetal nucleic acid from a maternal sample. The compositions and processes described herein are useful for non-invasive prenatal diagnostics, including the detection of chromosomal aneuploidies.
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 1/6804 - Nucleic acid analysis using immunogens
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6879 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for sex determination
The present application relates to a nucleic acid molecule having a nucleotide sequence encoding a bifunctional polypeptide comprising the DNA-binding domain of a protein belonging to the family of Methyl-CpG binding proteins (MBDs) and the Fc portion of an antibody. In addition, vectors and host cells which comprise said nucleic acid molecule and polypeptides which are encoded by said nucleic acid molecule as well as processes for producing said polypeptide are disclosed. Moreover, the present application provides an antibody specifically binding said polypeptide and compositions, in particular diagnostic compositions comprising the nucleic acid molecule(s), vector(s), host cell(s), polypeptide(s) or antibodie(s) of the present application. Furthermore, methods and uses employing the polypeptides of the present invention for detecting methylated DNA, in particular in tumorous tissue or tumor cells are provided.
C07K 14/00 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C07K 17/00 - Carrier-bound or immobilised peptides; Preparation thereof
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
76.
Methods and processes for non-invasive assessment of genetic variations
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
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
78.
Methods and compositions for the analysis of biological molecules
Provided herein are compositions and methods for analysis of nucleic acids, including, methods and compositions for genotyping, haplotyping, sequencing and performing other genetic and epigenetic analyses on nucleic acids, for example. In some embodiments, methods and compositions suitable for whole-genome sequencing on single molecules of nucleic acid are provided. In some embodiments, analysis of single molecules of nucleic acid are performed in conjunction with nanopores and/or nanopore devices.
Provided herein are methods and compositions to extract and enrich by, physical separation or amplification, relatively short nucleic acids from a nucleic acid composition containing a high background of longer nucleic acids (e.g., host or maternal nucleic acids; genomic nucleic acid and the like).
Provided herein are methods, compositions and kits to extract and relatively enrich by physical separation or amplification short base pair nucleic acid in the presence of a high background of genomic material (e.g., host or maternal nucleic acids).
Blood plasma of pregnant women contains fetal and (generally >90%) maternal circulatory extracellular DNA. Most of said fetal DNA contains ≦500 base pairs, said maternal DNA having a greater size. Separation of circulatory extracellular DNA of <500 base pairs results in separation of fetal from maternal DNA. A fraction of a blood plasma or serum sample of a pregnant woman containing, due to size separation (e.g. by chromatography, density gradient centrifugation or nanotechnological methods), extracellular DNA substantially comprising ≦500 base pairs is useful for non-invasive detection of fetal genetic traits (including the fetal RhD gene in pregnancies at risk for HDN; fetal Y chromosome-specific sequences in pregnancies at risk for X chromosome-linked disorders; chromosomal aberrations; hereditary Mendelian genetic disorders and corresponding genetic markers; and traits decisive for paternity determination) by e.g. PCR, ligand chain reaction or probe hybridization techniques, or nucleic acid arrays.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C07H 21/02 - 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 ribosyl as saccharide radical
82.
Methods and processes for non-invasive assessment of genetic variations
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
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
Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.
G06F 19/10 - Bioinformatics, i.e. methods or systems for genetic or protein-related data processing in computational molecular biology (in silico methods of screening virtual chemical libraries C40B 30/02;in silico or mathematical methods of creating virtual chemical libraries C40B 50/02)
G11C 17/00 - Read-only memories programmable only once; Semi-permanent stores, e.g. manually-replaceable information cards
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
G06F 19/18 - for functional genomics or proteomics, e.g. genotype-phenotype associations, linkage disequilibrium, population genetics, binding site identification, mutagenesis, genotyping or genome annotation, protein-protein interactions or protein-nucleic acid interactions
G06F 19/24 - for machine learning, data mining or biostatistics, e.g. pattern finding, knowledge discovery, rule extraction, correlation, clustering or classification
G06F 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
86.
Reducing sequence read count error in assessment of complex genetic variations
G06F 19/18 - for functional genomics or proteomics, e.g. genotype-phenotype associations, linkage disequilibrium, population genetics, binding site identification, mutagenesis, genotyping or genome annotation, protein-protein interactions or protein-nucleic acid interactions
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
G06F 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
87.
Methods and compositions for analyzing nucleic acid
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
G06F 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
G06F 19/24 - for machine learning, data mining or biostatistics, e.g. pattern finding, knowledge discovery, rule extraction, correlation, clustering or classification
88.
Methods and processes for non-invasive assessment of genetic variations
Provided herein are methods, processes, systems and apparatuses for non-invasive assessment of a chromosome aneuploidy in a fetus according to a comparison of ratios of counts of sequence reads mapped to certain chromosomes. Also provided herein are methods, processes, systems and apparatuses for non-invasive assessment of a copy number variation in a fetus.
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
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
89.
Methods and processes for non-invasive assessment of genetic variations
Provided herein are methods, processes and apparatuses for determining the fraction of fetal nucleic acid in a test sample derived from a pregnant female with improved accuracy and/or precision. Also, provided herein are methods, processes and apparatuses for determining the presence or absence of a genetic variation in a fetus with improved accuracy and/or precision. Certain methods include using fetal fraction measurements for the determination of a fetal genetic variation.
C12Q 1/683 - Hybridisation assays for detection of mutation or polymorphism involving restriction enzymes, e.g. restriction fragment length polymorphism [RFLP]
G06F 19/18 - for functional genomics or proteomics, e.g. genotype-phenotype associations, linkage disequilibrium, population genetics, binding site identification, mutagenesis, genotyping or genome annotation, protein-protein interactions or protein-nucleic acid interactions
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
90.
Methods and processes for non-invasive assessment of genetic variations
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
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
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.
G06F 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
G06F 19/18 - for functional genomics or proteomics, e.g. genotype-phenotype associations, linkage disequilibrium, population genetics, binding site identification, mutagenesis, genotyping or genome annotation, protein-protein interactions or protein-nucleic acid interactions
G06F 19/24 - for machine learning, data mining or biostatistics, e.g. pattern finding, knowledge discovery, rule extraction, correlation, clustering or classification
92.
Methods and processes for non-invasive assessment of genetic variations
C40B 20/00 - Methods specially adapted for identifying library members
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
Provided are methods for identifying the presence or absence of a chromosome abnormality by which a cell-free sample nucleic acid from a subject is analyzed. In certain embodiments, provided are methods for identifying the presence or absence of a fetal chromosome abnormality in a nucleic acid from cell-free maternal blood.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
G06F 19/20 - for hybridisation or gene expression, e.g. microarrays, sequencing by hybridisation, normalisation, profiling, noise correction models, expression ratio estimation, probe design or probe optimisation
95.
Methods and processes for non-invasive assessment of genetic variations
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
G06F 15/00 - Digital computers in general; Data processing equipment in general
96.
Methods and processes for non-invasive assessment of genetic variations
G06F 19/00 - Digital computing or data processing equipment or methods, specially adapted for specific applications (specially adapted for specific functions G06F 17/00;data processing systems or methods specially adapted for administrative, commercial, financial, managerial, supervisory or forecasting purposes G06Q;healthcare informatics G16H)
G06F 15/00 - Digital computers in general; Data processing equipment in general
G06F 19/18 - for functional genomics or proteomics, e.g. genotype-phenotype associations, linkage disequilibrium, population genetics, binding site identification, mutagenesis, genotyping or genome annotation, protein-protein interactions or protein-nucleic acid interactions
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
The technology relates in part to quantification of a minority nucleic acid species from a nucleic acid sample. In some embodiments, methods for determining the amount of fetal nucleic acid (e.g. absolute amount, relative amount) in a maternal sample are provided.
The technology relates in part to multimer conjugates comprising a scaffold linked to two or more polypeptides that specifically interact with a nucleic acid containing beta-D-glucosyl-hydroxymethylcytosine or beta-D-glucosyl-hydroxymethyluracil. The scaffold can be chosen from an antibody, an antibody fragment, a multimerized binding partner that interacts with a binding partner counterpart in each of the polypeptides, a polymer, and a polyfunctional molecule. The polypeptides can be from a kinetoplastid flagellate organism and may comprise a full-length native or modified protein or a fragment thereof that specifically interacts with the beta-D-glucosyl-hydroxymethylcytosine and/or the beta-D-glucosyl-hydroxymethyluracil in the nucleic acid. The conjugates provided herein can be used to detect the presence, absence or amount of beta-D-glucosyl-hydroxymethylcytosine and/or beta-D-glucosyl-hydroxymethyluracil-containing nucleic acid in a sample.
The technology relates in part to quantification of a minority nucleic acid species from a nucleic acid sample. In some embodiments, methods for determining the amount of fetal nucleic acid (e.g. absolute amount, relative amount) in a maternal sample are provided.
The technology relates in part to quantification of a minority nucleic acid species from a nucleic acid sample. In some embodiments, methods for determining the amount of fetal nucleic acid (e.g. absolute amount, relative amount) in a maternal sample are provided.
patents
