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.
Provided herein are bioinformatic tools and processes used to classify the presence or absence of genetic mosaicism for a copy number variation in one or more fetuses (e.g., predict whether one fetus or more than one fetus is affected with the copy number variation). Sample nucleic acid is subjected to a sequencing process and the resulting sequence reads are analyzed to identify a genetic copy number variation region. A genetic mosaicism for the copy number variation region is classified for one fetus or more than one fetus based on: (i) a mosaicism ratio of a fraction of nucleic acid having the copy number variation region to a fraction of fetal nucleic acid, and (ii) the chromosome having the genetic copy number variation region (e.g., the type of aneuploidy identified) or (ii) a number of fetuses being carried by the pregnant female.
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. Optionall the nucleic acid is genomic DNA.
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
4.
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 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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
5.
METHODS AND PROCESSES FOR ASSESSMENT OF GENETIC MOSAICISM
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.
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.
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
7.
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.
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 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
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.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
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
9.
METHODS FOR NON-INVASIVE ASSESSMENT OF COPY NUMBER 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.
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
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.
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
11.
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.
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
Technology provided herein relates in part to methods, processes, machines and apparatuses for detecting genetic variations. In some embodiments, the technology is related to non-invasive assessment of aneuploidies.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
G06F 19/00 - 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)
13.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF 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
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
14.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF GENETIC VARIATIONS
Methods, processes and apparatuses for non-invasive assessment of genetic variations. The invention may make use of nucleic acid fragments from circulating cell free nucleic acid. The methods are based on partitioning one or more genomic regions of a reference genome into a plurality of portions according to the coverage variability (proportionality), the local fetal fraction and/or the CG profile.
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
15.
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.
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
Technology described herein pertains in part to diagnostic tests that make use of sequence reads generated by a sequencing process. In some embodiments, a component used to generate a chromosome representation can be based on counts of sequence reads not aligned to a reference genome.
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 19/22 - 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
G06F 19/24 - for machine learning, data mining or biostatistics, e.g. pattern finding, knowledge discovery, rule extraction, correlation, clustering or classification
17.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF GENETIC VARIATIONS
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 1/68 - 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 19/18 - 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
19.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF 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
20.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF GENETIC VARIATIONS
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 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
21.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF GENETIC VARIATIONS
Provided herein are methods for non-invasive assessment of genetic variations. The methods are based on mapped sequence reads and make use of decision analyses. The decision analyses sometimes include segmentation analyses and/or odds ratio analyses.
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
22.
GENETIC MARKERS FOR MACULAR DEGENERATION DISORDER TREATMENT
Provided in part herein are genetic variations (e.g., single nucleotide polymorphisms), in particular the specific SNPs rs1870377, rs2071559, rs2305948 in the gene KDR and the specific SNPs rs3025033 and rs3025039 in the gene VEGFA, associated with a vascular endothelial growth factor (VEGF) suppression response to an anti-VEGF agent for treatment of a macular degeneration disorder (e.g., age-related macular degeneration (AMD)). Also provided herein are methods for determining a genotype that includes such genetic variations, methods for predicting a VEGF suppression response for a subject according to a genotype, and methods for selecting a treatment suitable for treating a macular degeneration disorder (e.g., wet AMD) for a subject in need thereof according to a genotype.
The invention relates to a collection of primer pairs that may be used for identifying hypermethylated genomic loci characterized by criteria such as the number of CpG methylation sites, the density of methylation-sensitive restriction sites and the degree of methylation
The technology relates in part to selection, quantification and use of particular nucleic acid markers. In some embodiments, such markers are particular epigenetic markers, and sometimes each marker is a particular methylation state of a nucleic acid locus.
A method and system for analyzing circulating cell-free nucleic acids from a pregnant female with reduced bias. Counts of sequnce 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 analsis, such as the detection of fetal aneuploidy.
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 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
The invention is directed to a method of selecting disease-correlated clonotypes that have a reduced likelihood of producing a false positive signal of relapse when used to monitor minimal residual disease. In accordance with the invention, candidate correlating clonotypes are obtained from a patient, the rarity of each is determined either by comparison with a clonotype database or a clonotype model, and one or more of the rarest of such clonotypes are used to monitor the minimal residual disease.
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 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
28.
MONITORING MANTLE CELL LYMPHOMA CLONOTYPES IN PERIPHERAL BLOOD AFTER IMMUNOTRANSPLANT
The invention is directed to a method of monitoring a mantle cell lymphoma residual disease in an immunotransplant patient by post-treatment analysis of clonotype profiles from patient blood samples. In some embodiments, methods of the invention comprising steps of (a) treating a patient by immunotransplanting the patient with vaccine-primed autologous T cells; (b) obtaining a peripheral blood sample from the patient comprising B-cells and/or cell-free nucleic acids; (c) amplifying molecules of nucleic acid from the B-cells of the sample and/or cell-free nucleic acids in the sample, the molecules of nucleic acid comprising recombined DNA sequences from immunoglobulin genes; (d) sequencing the amplified molecules of nucleic acid to form a clonotype profile; and (e) determining from the clonotype profile a presence, absence and/or level of the one or more patient-specific clonotypes correlated with the mantle cell lymphoma, including phylogenic clonotypes thereof.
The invention is directed to sequencing-based methods for monitoring a minimal residual disease of a plasma cell proliferative disorder, such as multiple myeloma and/or MGUS, by one or more clonotypes correlated with the disorder. In some embodiments, such methods comprise the following steps: (a) obtaining a sample of peripheral blood from the patient; (b) amplifying molecules of nucleic acid from the sample, the molecules of nucleic acid comprising recombined DNA sequences from immunoglobulin genes; (c) sequencing the amplified molecules of nucleic acid to form a clonotype profile; and (d) determining from the clonotype profile a presence, absence and/or level of one or more patient-specific clonotypes correlated with the plasma cell proliferative disorder and phylogenic clonotypes thereof.
The invention is directed to sequencing-based methods for monitoring a minimal residual disease of a diffuse large B cell lymphoma (DLBCL) by one or more clonotypes correlated with the disorder. In some embodiments, such methods comprise the following steps: (a) obtaining a sample of peripheral blood from the patient; (b) amplifying molecules of nucleic acid from the sample, the molecules of nucleic acid comprising recombined DNA sequences from immunoglobulin genes; (c) sequencing the amplified molecules of nucleic acid to form a clonotype profile; and (d) determining from the clonotype profile a presence, absence and/or level of one or more patient-specific clonotypes correlated with the DLBCL and phylogenic clonotypes thereof.
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
33.
HIGH SENSITIVITY MUTATION DETECTION USING SEQUENCE TAGS
The invention is directed to methods for increasing the sensitivity of high throughput sequencing, particularly for distinguishing true rare mutations from amplification, sequencing and other sample processing errors that occur in sequencing techniques. In one aspect, methods of the invention includes steps of (a) preparing templates from nucleic acids in a sample; (b) labeling by sampling the templates to form tag-template conjugates, wherein substantially every template of a tag-template conjugate has a unique sequence tag; (c) linearly amplifying the tag- template conjugates; (d) generating a plurality of sequence reads from the linearly amplified tag- template conjugates; and (e) determining a nucleotide sequence of each of the nucleic acids based on the frequencies, or numbers, of each type of nucleotide at each nucleotide position of each plurality of sequence reads having identical sequence tags.
The invention provides a method of making measurements on individual cells of a population by forming reactors containing single cells and a predetermined number, usually one, homogeneous sequence tag. In one aspect, the invention provides a method of making multiparameter measurements on individual cells of such a population by carrying out a polymerase cycling assembly (PCA) reaction to link their identifying nucleic acid sequences, such as sequence tag copies derived from a homogeneous sequence tag, to other cellular nucleic acids of interest, thereby forming fusion products. The fusion products of such PCA reactions are then sequenced and tabulated to generate multiparameter data for cells of the population.
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.
The invention is directed to the use of sequence tags to improve sequence determination of amplicons of related sequences, particularly large and complex amplicons, such as those comprising recombined nucleic acids encoding immune receptor molecules. In one aspect, sequence reads having the same sequence tags are aligned after which final base calls are determined from a (possibly weighted) average base call from sequence read base calls at each position. Similarly, in another aspect, sequence reads comprising series of incorporation signals are aligned by common sequence tags and base calls in homopolymer regions are made as a function incorporation signal values at each "flow" position.
The invention is directed to a prognostic indicator for CLL patients who have undergone an allogeneic stem cell transplant (SCT). The indicator is based on a method of monitoring levels and changes in levels of correlating clonotypes of the CLLs at successive time points. The prognostic indicator applies to patients who have survived for at least one year from an allogeneic SCT and includes criteria based on the following two measurements: (a) frequency of CLL correlating clonotypes (e.g. in terms of number per 106 clonotypes) in an initial clonotype profile (from peripheral blood), and (b) fold change in such CLL correlating clonotype number between such initial measurement and a successively measured clonotype profile.
The invention is directed to methods of monitoring B-cell lymphoid proliferative disorders, such as B-cell acute lymphoblastic leukemias, by measuring the presence, absence and/or levels of correlating, or index, clonotypes and related clonotypes that have evolved therefrom, for example, as part of the disease condition. In one aspect, such methods are implemented by generating sequencing-based clonotype profiles and determining frequencies of correlating, or index, clonotypes present, including new clonotypes that have evolved therefrom, particularly, in the case of B-cell ALL, by VH substitution. The invention also includes use of such monitoring information to modify treatment status of a patient.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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
43.
DETECTION AND QUANTITATION OF SAMPLE CONTAMINATION IN IMMUNE REPERTOIRE ANALYSIS
The invention is directed to methods for detecting and quantifying nucleic acid contamination in a tissue sample of an individual containing T cells and/or B cells, which is used for generating a sequence-based clonotype profile. In one aspect, the invention is implemented by measuring the presence and/or level of an endogenous or exogenous nucleic acid tag by which nucleic acid from an intended individual can be distinguished from that of unintended individuals. Endogenous tags include genetic identity markers, such as short tandem repeats, rare clonotypes or the like, and exogenous tags include sequence tags employed to determine clonotype sequences from sequence reads.
The invention is direct to a method for determining a cancer patient's immune responsiveness to anti-cancer vaccination. In one aspect, for each of a plurality of vaccinations, pairs of clonotype profiles are obtained, one immediately prior to vaccination and one during the period of peak immune response, usually within two to twenty days after the vaccination. Responsiveness is correlated to successive increases in identical clonotypes within each pair of clonotype profiles in at least two successive vaccinations.
The invention is directed to methods for determining nucleic acids that encode immune receptor chains originating from the same cell, that is, paired immune receptor chains. Methods of the invention comprise high-throughput sequencing of rearranged nucleic acids encoding immune receptors from one or more samples of lymphocytes. In one aspect, from a plurality of subsets of a sample, nucleic acids encoding separate chains of a pair are separately sequenced, wherein the size of the sample and the number of subsets are selected so that the distribution of lymphocytes approximates a binomial model. Paired chains are determined by identifying pairs that appear together or that are entirely absent in the subsets.
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
48.
MONITORING TRANSFORMATION OF FOLLICULAR LYMPHOMA TO DIFFUSE LARGE B-CELL LYMPHOMA BY IMMUNE REPERTOIRE ANALYSIS
The invention is directed to a method of prognosing in an individual a transformation from follicular lymphoma to diffuse large B-cell lymphoma (DLBCL) by measuring changes and/or lack of changes in certain groups of related clonotypes, referred to herein as "clans," in successive clonotype profiles of the individual. A clan may arise from a single lymphocyte progenitor that gives rise to many related lymphocyte progeny, each possessing and/or expressing a slightly different immunoglobulin receptor due to somatic mutation(s), such as base substitutions, inversions, related rearrangements resulting in common V(D)J gene segment usage, or the like. A higher likelihood of transformation from follicular lymphoma to DLBCL is correlated with the persistence of clans in successive clonotype profiles whose clonotype membership fails to undergo diversification over time.
The invention is directed to a method of detecting immune activation in an individual by measuring frequencies and sizes of certain groups of related clonotypes, referred to herein as "clans," in a clonotype profile of the individual. A clan may arise from a single lymphocyte progenitor that gives rise to many related lymphocyte progeny, each possessing and/or expressing a slightly different immunoglobulin receptor due to somatic mutation(s), such as base substitutions, inversions, related rearrangements resulting in common V(D)J gene segment usage, or the like. Immune activation is correlated to frequencies and sizes of clans in a clonotype profile exceeding reference values for those features.
The present invention is drawn to methods for measuring numbers, levels, and/or ratios of cells, such as lymphocytes, infiltrated into a solid tissue, such as a tumor or a tissue affected by an autoimmune disease, and to methods for making patient prognoses based on such measurements. In one aspect, methods of the invention comprise sorting lymphocytes from an accessible tissue, such as peripheral blood, into functional subsets, such as cytotoxic T cells and regulatory T cells, and generating clonotype profiles of each subset. An inaccessible disease- affected tissue is sampled and one or more clonotype profiles are generated. From the latter clonotype profiles, levels lymphocytes in each of the functional subsets are determined in the disease-affected tissue by their clonotypes, which are identified from lymphocytes sorted into subsets from the accessible tissue.
The invention is directed to methods for biometrically identifying or distinguishing biological specimens, such as patient specimens, as being from the same or different individuals by analysis of specimen clonotypes. The invention provides a direct or backup method for determining or confirming specimen identities. In one aspect, a method of the invention includes generating a first clonotype profile from a first specimen and forming therefrom an identifier set of clonotypes, which serves as a molecular fingerprint of the first specimen. Other specimens are determined to be from the same source individual or from a different source individual by generating clonotype profiles from such specimens and determining the presence or absence in such profiles of clonotypes of the identifier set of the first specimen.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C12Q 1/04 - Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
The invention is directed to methods for measuring immune activation by the level of clonotypes having the same unique regions and different isotype-determining regions. In one aspect, the method of the invention comprises forming a sequence-based clonotype profile from a sample containing B lymphocytes, wherein each clonotype of such profile comprises a unique region, such as a portion of a VDJ segment, and an isotype determining region, such as a portion of a C gene segment. Immune activation is indicated whenever the level of such clonotypes exceeds an upper bound of a reference range determined from multiple individual measurements or population measurements.
The invention includes a method for determining the disease status of an individual suffering from ankylosing spondylitis by monitoring the individual's T-cell repertoire for the presence and/or level of clonotypes encoding T-cell receptor chains with segments identical to and/or related to the peptide LCASSLEASGSSYNEQFFGPGTRLTV (SEQ ID NO: 1) or the peptide VYFCASSDSSGSTDTQYFGPGTRLTV (SEQ ID NO: 2). The invention also includes therapeutic antibodies specific for these peptides for ameliorating the effects of ankylosing spondylitis.
The invention is directed to a method of screening patients suffering from an autoimmune disease for responsiveness to treatment with a disease modifying anti-rheumatic drug, or DMARD. In some embodiments the method of the invention comprises the steps of (a) measuring an IgH clonotype profile from B-cells in a sample of tissue affected by the autoimmune disease, the IgH clonotype profile including IgH clonotypes, IgG clonotypes, and IgD clonotypes; and (b) classifying a patient as being more likely to respond to DMARD treatment, whenever the patient has, with respect to reference levels characteristic of normal tissue, elevated IgH concentration, elevated IgG fraction, and reduced IgD fraction.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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
57.
METHODS AND PROCESSES FOR NON-INVASIVE ASSESSMENT OF 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
The invention is directed to methods of measuring an immune response by comparing sequence-based clonotype frequency data from successively measured clonotype profiles. In particular, the invention includes immunotherapies of cancers, such as lymphomas, that include sensitive pre- and post-vaccination sequence-based measurements of changes in a patient's immune repertoire, thereby providing a sensitive measure of the likelihood of treatment success.
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.
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
60.
PRODUCTS AND PROCESSES FOR MULTIPLEX NUCLEIC ACID IDENTIFICATION
Provided herein are products and processes for detecting the presence or absence of multiple target nucleic acids. Certain methods include amplifying the target nucleic acids, or portion thereof; extending oligonucleotides that specifically hybridize to the amplicons, where the extended oligonucleotides include a capture agent; capturing the extended oligonucleotides to a solid phase via the capture agent; releasing the extended oligonucleotide by competition with a competitor; detecting the extended oligonucleotide, and thereby determining the presence or absence of each target nucleic acid by the presence or absence of the extended oligonucleotide.
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 methods employ inhibitory oligonucleotides for reducing the efficiency of the amplification of the dominant nucleic acid and/or target competitors for improving the quantification.
Provided herein are fetal diagnostic methods, kits and computational products useful for non- invasively detecting genetic variations for which maternal nucleic acid sequences are utilized as a reference.
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 19/26 - for data visualisation, e.g. graphics generation, display of maps or networks or other visual representations
64.
COMPLEMENT FACTOR H COPY NUMBER VARIANTS FOUND IN THE RCA LOCUS
Provided herein are compositions and processes that allow for sensitive detection of up to fifteen individual HPV sequences or types in a single, multiplexed test. High risk types that can be detected are HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 73. Processes and compositions described herein are based in part on the presence or absence of HPV nucleic acid, including HPV DNA and RNA.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
C12Q 1/04 - Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
66.
MONITORING HEALTH AND DISEASE STATUS USING CLONOTYPE PROFILES
There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer, especially lymphoid neoplasms, such as lymphomas and leukemias. Provided herein are methods for using DNA sequencing to identify personalized, or patient-specific biomarkers in patients with lymphoid neoplasms, autoimmune disease and other conditions. Identified biomarkers can be used to determine and/or monitor the disease state for a subject with an associated lymphoid disorder or autoimmune disease or other condition. In particular, the invention provides a sensitive method for monitoring lymphoid neoplasms that undergo clonal evolutions without the need to development alternative assays for the evolved or mutated clones serving as patient-specific biomarkers.
Methods of generating sequence profiles of populations of nucleic acids, whose member nucleic acids contain regions of high variability, such as populations of nucleic acids encoding T cell receptors or B cell receptors are presented. In addition, pluralities of sets of primers for generating nested sets of templates from nucleic acids in such populations are provided, thereby insuring the production of at least one template from which sequence reads are generated, despite such variability, or despite limited lengths or quality of sequence reads. Furthermore, members of such populations are bidirectionally sequenced so that further sequence information is obtained by analyzing overlapping sequence reads in the zones of highest variability.
The invention generally relates to methods for detecting fetal nucleic acids and methods for diagnosing fetal abnormalities. In certain embodiments, the invention provides methods for determining whether fetal nucleic acid is present in a maternal sample including obtaining a maternal sample suspected to include fetal nucleic acids, and performing a sequencing reaction on the sample to determine presence of at least a portion of a Y chromosome in the sample, thereby determining that fetal nucleic acid is present in the sample. In other embodiments, the invention provides methods for quantitative or qualitative analysis to detect fetal nucleic acid in a maternal sample, regardless of the ability to detect the Y chromosome, particularly for samples including normal nucleic acids from a female fetus.
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
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
G06F 17/00 - Digital computing or data processing equipment or methods, specially adapted for specific functions
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)
70.
FETAL GENOMIC ANALYSIS FROM A MATERNAL BIOLOGICAL SAMPLE
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.
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 aneuplodies.
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).
Described herein are products and processes for nucleic acid quantification, which are in part useful for detecting and determining the nucleotide sequence of rare nucleic acids (i.e., low copy number nucleic acids) in a sample. Such products and processes are useful for reducing the dynamic range among different nucleic acid species.
Provided herein are products and processes for detecting the presence or absence of multiple target nucleic acids. Certain methods include amplifying the target nucleic acids, or portion thereof; extending oligonucleotides that specifically hybridize to the amplicons, where the oligonucleotides include distinguishable labels and a capture agent; capturing the extended oligonucleotides to a solid phase via the capture agent; releasing and detecting the distinguishable label, and thereby determining the presence or absence of each target nucleic acid by the presence or absence of the distinguishable label.
There is a need for improved methods for determining the diagnosis and prognosis of patients with conditions, including autoimmune disease and cancer. Provided herein are methods for using DNA sequencing to identify personalized biomarkers in patients with autoimmune disease and other conditions. Identified biomarkers can be used to determine the disease state for a subject with an autoimmune disease or other condition.
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 aneuplodies.
Provided in part herein is an improved method for the detection of specific polymorphic alleles in a mixed DNA population. The method comprises enriching the relative percentage of a given polymorphic allele that is exponentially amplifiable by PCR. Provided also are methods for selectively enriching target nucleic acid, for example, fetal nucleic acid in a maternal sample. In the case of detecting fetal nucleic acid in a maternal sample, a restriction enzyme is introduced that can discriminate between the alleles of a polymorphic site. In some embodiments, the maternal allele is digested and nucleic acid comprising the paternal allele is relatively enriched.
Provided herein are compositions, processes and kits for noninvasive, early determination of fetal sex from, and/or amount of fetal nucleic acid in, an extracellular nucleic acid sample from a pregnant female. Such compositions, processes and kits are useful for detection of low genomic copy numbers of male fetal nucleic acid in a high copy number background of female nucleic acid, thereby determining the sex of a fetus and/or amount of fetal nucleic acid in a sample.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
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
80.
SINGLE MOLECULE NUCLEIC ACID SEQUENCE ANALYSIS PROCESSES AND COMPOSITIONS
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 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.
The invention provides a novel additive for improved analysis by mass spectrometry. More specifically, ascorbic acid has been found to reduce or eliminate the presence of adducts commonly present in mass spectra. The improved processes and compositions of the invention allow for increased accuracy, sensitivity and throughput for samples analyzed by mass spectrometry.
The present invention is directed in part to a method for detecting a target nucleic acid using detector oligonucleotides detectable by mass spectrometry. This method takes advantage of the 5' to 3' nuclease activity of a nucleic acid polymerase to cleave annealed oligonucleotide probes from hybridized duplexes and releases labels for detection by mass spectrometry. This process is easily incorporated into a polymerase chain reaction (PCR) amplification assay. The method also includes embodiments directed to quantitative analysis of target nucleic acids.
Embodiments include integrated robotic sample transfer devices and components thereof which are used for reliably and accurately transferring small samples of material from one registered position to another registered position. Such transfers of material may be carried out by a single pin tool or an array of pin tools of a pin tool head assembly of robotic sample transfer devices. Some embodiments also include automated cleaning of the pin tools used to transfer the sample material. Some embodiments are fully integrated units having internal fluid supply and waste tanks, vacuum source, fluid pumps, controllers and user interface devices.
Provided herein are methods and kits for the separation, extraction and enrichment of short- stranded nucleic acid in the presence of a high background of long-stranded genomic material (e.g., host or maternal nucleic acids). The methods rely on primers that selectively bind to the long- stranded nucleic acid, whereby the primers may be used to subsequently separate the long and short nucleic acid.
Provided herein are products and processes for the amplification, detection and sequencing of short-stranded nucleic acid in the presence of a high background of long-stranded genomic material (e.g., host or maternal nucleic acids). The methods rely on the use of inside and outside primers introduced at varying concentrations, as well as universal amplification reactions that preferentially amplify short, low copy number nucleic acid.
The invention relates to methods for the detection and/or diagnosis of fetal chromosomal abnormalities. In particular, the invention concerns the diagnosis of fetal chromosomal abnormalities by combining free, fetal nucleic acid-based tests with other one or more non-free, fetal nucleic acid-based chromosomal abnormality tests.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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
88.
DETECTION AND QUANTIFICATION OF BIOMOLECULES USING MASS SPECTROMETRY
The present invention is directed in part to a method for detecting a target nucleic acid using detector oligonucleotides detectable by mass spectrometry. This method uses the 5' to 3' nuclease activity of a nucleic acid polymerase to cleave annealed oligonucleotide probes from hybridized duplexes and release labels for detection by mass spectrometry. This process is easily incorporated into a PCR amplification assay. The method also includes embodiments directed to quantitative analysis of target nucleic acids.
Provided herein are processes for rapidly identifying or determining sequence information in a sample nucleic acid by comparing sample nucleic acid sequence information to reference nucleic acid sequence information or information obtained from reference samples. Also provided are automated systems for conducting comparative sequence analyses.
Provided is an improved method for the detection of specific polymorphic alleles in a mixed DNA population. The method comprises enriching the relative percentage of a given polymorphic allele that is exponentially amplifiable by PCR. Also provided are methods for selectively enriching target nucleic acid, for example, fetal nucleic acid in a maternal sample. In the case of detecting fetal nucleic acid in a maternal sample, a restriction enzyme is introduced that can discriminate between the alleles of a polymorphic site. Preferably, the maternal allele is digested and nucleic acid comprising the paternal allele is relatively enriched.
The present invention provides evidence that PRC2 target methylation is present in multiple forms of cancer. In six out of seven tumor types, hypermethylated genes were found to have promoters that are enriched for PRC2 targets. Thus, featured herein are compositions and methods for treating cancer. In one aspect, methods are provided for blocking the binding of all or part of a PRC2 complex to a nucleic acid target gene region that comprises one or more PRC2 binding sites.
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
93.
NUCLEIC ACID-BASED TESTS FOR RHD TYPING, GENDER DETERMINATION AND NUCLEIC ACID QUANTIFICATION
The invention in part provides nucleic acid-based assays, which are particularly useful for non-invasive prenatal testing. The invention in part provides compositions and methods for RhD typing, detecting the presence of fetal nucleic in a sample, determining the relative amount of fetal nucleic acid in a sample and determining the sex of a fetus, wherein each of the assays may be performed alone or in combination.
The present invention is directed to methods useful for determining DNA quality after bisulfite treatment. The methods include a PCR-based assay, which allows ab-initio assessment of the DNA quality after bisulfite treatment and can help to prevent inaccurate quantitative measurement resulting from poor bisulfite treatment.
Methods and kits for the amplification, detection and quantification of a nucleic acid from a sample are disclosed The methods of the invention may be used in a wide range of applications, including, but not limited to, the detection and quantification of fetal nucleic acid from maternal plasma, the detection and quantification of circulating nucleic acids from neoplasms (malignant or non-malignant), accurate pooling analysis for low frequency alleles, or any other application requinng sensitive quantitative analysis of nucleic acids
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).
A large scale DNA methylation study was perfomred in patients with acute myeloid leukemia (AML) that revealed quantitative methylation patterns correlated with patient survival. Based on these results, a prognostic model was built which categorizes a patient's risk - either in a good or poor prognosis group. The findings provided herein support the use of genomic methylation markers for improved molecular classification and disease management in adult AML. Also, the results provide insight into the pathophysiology of AML and offer novel AML gene targets. Thus provided are methods and compositions for the prognosis of a subject suffering from acute myeloid leukemia (AML) based on the methylation state of nucleic acids. The methods may used alone to determine a patient's prognosis or in combination with other prognostic factors or markers such as gene expression.
The present invention provides a novel class of molecules, termed 旜compomers”, that enable the indirect detection of target molecules, as well as novel target detection reagents and compomer templates that encode compomers. Compomers are linear polymers generated from the compomer template portion of a target detection reagent during the course of an assay. In a given assay, each compomer species is correlated with a different target molecule, e.g., a carbohydrate, lipid, polypeptide, or target nucleic acid, particularly a specific nucleotide sequence within a target nucleic acid molecule. When, for example, a target nucleic acid is present in an assay, a compomer species specifically and uniquely correlated with the particular target (e.g., a known SNP or other genetic variant) is generated directly from a target-specific detection reagent (or indirectly from a larger precursor encoded by the compomer template and from which it is subsequently released), after which it can readily be detected, even in an assay where tens, hundreds, or thousands of different compomer species may be generated, as each compomer species is engineered to differ from the others by a small, resolvable defined characteristic (e.g., a mass increment, a difference in subunit composition, sequence, size, length, etc.). When coupled with highly sensitive detection techniques (e.g., MALDI-TOF mass spectrometry, nucleic acid hybridization, nuclear magnetic resonance, etc.), a large number of different compomer species can be detected in a single reaction, thereby facilitating highly multiplexed analyses of complex samples.
Provided herein are methods for identifying a risk of low BMD in a subject, reagents and kits for carrying out the methods, methods for identifying candidate therapeutics for treating low BMD-related disorders, such as osteoporosis, and therapeutic and preventative methods applicable to osteoporosis. These embodiments are based upon an analysis of polymorphic variations in nucleotide sequences within the human genome.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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
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
100.
METHODS FOR IDENTIFYING RISK OF BREAST CANCER OR PROSTATE CANCER AND TREATMENTS THEREOF
Provided herein are methods for identifying a subject at risk of breast cancer or prostate cancer, methods for providing a prognosis to a subject at risk of breast cancer or suffering from breast cancer, reagents and kits for carrying out the methods, methods for identifying candidate therapeutics for treating breast cancer or prostate cancer, and therapeutic methods for treating breast cancer or prostate cancer in a subject. These embodiments are based upon and analysis of polymorphic variations in nucleotide sequences within the human genome.
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 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
patents
