This disclosure provides a predictive risk assessment tools to determine personalized risk of multiple diseases in a subject using microbiome. Current risk prediction test using microbiome may only detect one disease or health condition at a time. By determining multiple diseases simultaneously, the disclosed techniques can provide a cost-effective method to support clinical decision making, and hence to help improve disease prevention and management.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
2.
SMALL MOLECULE INHIBITOR TARGETING A LEUKEMIC STEM CELL ASSOCIATED GENE FOR HIGH-RISK AML PATIENTS
Disclosed a method of identifying high-risk Acute Myeloid Leukemia patients based upon the expression of a leukemic stem-cell (LSC) associated gene known as Serine Protease Inhibitor Kazal type 2 (SPINK2), the method including: (i) Immunohistochemistry (IHC)-based detection of SPINK2 protein expression, (ii) quantification of SPINK2 expression using a scoring system (range 0-16), whereby high SPINK2 is defined as a score>3 and (iii) utilization of the score to classify patients as high-risk (score>3) or low risk (score 0-3). Additionally, disclosed is a method of treating AML using a small molecule inhibitor (SMI) that selectively targets a domain of SPINK2 protein in leukemic cells highly expressing SPINK2; wherein the SMI reduces SPINK2 protein expression, alters SPINK2 target gene mRNA expression, inhibits SPINK2 function and consequently LSC proliferation/survival. A method of identifying potential candidates for SPINK2-SMI therapy to enhance treatment outcomes, whereby potential candidates refer to patients with high SPINK2 expression, is also disclosed.
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
A61K 31/403 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
Cell-free DNA molecules in a mixture of a biological sample can be analyzed to detect viral DNA. Methylation of viral DNA molecules at one or more sites in the viral genome can be determined. Mixture methylation level(s) can be measured based on one or more amounts of the plurality of cell-free DNA molecules methylated at a set of site(s) of the particular viral genome. The mixture methylation level(s) can be determined in various ways, e.g., as a density of cell-free DNA molecules that are methylated at a site or across multiple sites or regions. The mixture methylation level(s) can be compared to reference methylation level(s), e.g., determined from at least two cohorts of other subjects. The cohorts can have different classifications (including the first condition) associated with the particular viral genome. A first classification of whether the subject has the first condition can be determined based on the comparing.
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 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
4.
DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING
Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
Various applications can use fragmentation patterns related of cell-free DNA, e.g., plasma DNA and serum DNA. For example, the end positions of DNA fragments can be used for various applications. The fragmentation patterns of short and long DNA molecules can be associated with different preferred DNA end positions, referred to as size-tagged preferred ends. In another example, the fragmentation patterns relating to tissue-specific open chromatin regions were analyzed. A classification of a proportional contribution of a particular tissue type can be determined in a mixture of cell-free DNA from different tissue types. Additionally, a property of a particular tissue type can be determined, e.g., whether a sequence imbalance exists in a particular region for a tissue type or whether a pathology exists for the tissue type.
Methods and systems described herein involve using long cell-free DNA fragments to analyze a biological sample from a pregnant subject. The status of methylated CpG sites and single nucleotide polymorphisms (SNPs) is often used to analyze DNA fragments of a biological sample. A CpG site and a SNP are typically separated from the nearest CpG site or SNP by hundreds or thousands of base pairs. Finding two or more consecutive CpG sites or SNPs on most cell-free DNA fragments is improbable or impossible. Cell-free DNA fragments longer than 600 bp may include multiple CpG sites and/or SNPs. The presence of multiple CpG sites and/or SNPs on long cell-free DNA fragments may allow for analysis than with short cell-free DNA fragments alone. The long cell-free DNA fragments can be used to identify a tissue of origin and/or to provide information on a fetus in a pregnant female.
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
7.
COMBINED SIZE- AND COUNT-BASED ANALYSIS OF MATERNAL PLASMA FOR DETECTION OF FETAL SUBCHROMOSOMAL ABERRATIONS
An aberration in a fetal genome can be identified by analyzing a sample of fetal and maternal DNA. Classifications of whether an aberration (amplification or deletion) exists in a subchromosomal region are determined using count-based and size-based methods. The count classification and the size classification can be used in combination to determine whether only the fetus or only the mother, or both, have the aberration in the subchromosomal region, thereby avoiding false positives when the mother has the aberration and the fetus does not.
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
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
8.
NONINVASIVE PRENATAL GENOTYPING OF FETAL SEX CHROMOSOMES
Methods, apparatuses, and system are provided for analyzing a maternal sample to determine whether a male fetus of a pregnant female has inherited an X-linked mutation from the mother. A percentage of fetal DNA in the sample is obtained, and cutoff values for the two possibilities (fetus inherits mutant or normal allele) are determined. A proportion of mutant alleles relative to a normal allele on the X-chromosome can then be compared to the cutoff values to make a classification of which allele is inherited. Alternatively, a number of alleles from a target region on the X-chromosome can be compared to a number of alleles from a reference region on the X-chromosome to identify a deletion or amplification. The fetal DNA percentage can be computed by counting reactions with a fetal-specific allele, and correcting the number to account for a statistical distribution among the reactions.
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
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 biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
The present disclosure describes techniques for measuring quantities (e.g., relative frequencies) of sequence end motifs of cell-free DNA fragments in a biological sample of an organism for measuring a property of the sample (e.g., fractional concentration of clinically-relevant DNA) and/or determining a condition of the organism based on such measurements. Different tissue types exhibit different patterns for the relative frequencies of the sequence end motifs. The present disclosure provides various uses for measures of the relative frequencies of sequence end motifs of cell-free DNA, e.g., in mixtures of cell-free DNA from various tissues. DNA from one of such tissue may be referred to as clinically-relevant 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
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
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
10.
COMPOSITIONS FOR ENHANCING IMMUNOTHERAPY EFFICACY IN COLORECTAL CANCER TREATMENT
A composition for use in enhancing efficacy of immunotherapy for colorectal cancer in a subject in need thereof includes an effective amount of (1) any one or more of Lactobacillus gallinarum. Roseburia intestinalis, and Streptococcus salivarius K12; and (2) a physiologically acceptable excipient.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
11.
METHYLATION PATTERN ANALYSIS OF TISSUES IN A DNA MIXTURE
The contributions of different tissues to a DNA mixture are determined using methylation levels at particular genomic sites. Tissue-specific methylation levels of M tissue types can be used to deconvolve mixture methylation levels measured in the DNA mixture, to determine fraction contributions of each of the M tissue types. Various types of genomic sites can be chosen to have particular properties across tissue types and across individuals, so as to provide increased accuracy in determining contributions of the various tissue types. The fractional contributions can be used to detect abnormal contributions of a particular tissue, indicating a disease state for the tissue. A differential in fractional contributions for different sizes of DNA fragments can also be used to identify a diseased state of a particular tissue. A sequence imbalance for a particular chromosomal region can be detected in a particular tissue, e.g., identifying a location of a tumor.
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
Methods are provided for diagnosing pregnancy-associated disorders, determining allelic ratios, determining maternal or fetal contributions to circulating transcripts, and/or identifying maternal or fetal markers using a sample from a pregnant female subject. Also provided is use of a gene for diagnosing a pregnancy-associated disorder in a pregnant female subject.
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
Techniques are provided for detecting hematological disorders using cell-free DNA in a blood sample, e.g., using plasma or serum. For example, an assay can target one or more differentially-methylated regions specific to a particular hematological cell lineage (e.g., erythroblasts). A methylation level can be quantified from the assay to determine an amount of methylated or unmethylated DNA fragments in a cell-free mixture of the blood sample. The methylation level can be compared to one or more cutoff values, e.g., that correspond to a normal range for the particular hematological cell lineage as part of determining a level of a hematological disorder.
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential 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
C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
14.
NONINVASIVE PRENATAL MOLECULAR KARYOTYPING FROM MATERNAL PLASMA
Disclosed herein are methods, systems, and apparatus for estimating a fetal DNA percentage in a biological sample. In some embodiments, methods may include receiving one or more sequence tags for each of a plurality of DNA fragments in the biological sample. In addition, methods may include determining genomic positions for the sequence tags. Also, methods may include for each of one or more genomic regions, determining, with a computer system, a respective amount of DNA fragments within the genomic region from sequence tags having genomic positions within the genomic region; normalizing the respective amount to obtain a respective density; and comparing the respective density to a reference density to identify whether the respective density is statistically different from the reference density. Further, methods may include estimating the fetal DNA percentage from the one or more genomic regions identified to have respective densities statistically different than the reference densities.
Particular forward and reverse primers may be used to link distant regions of the same large DNA molecule into a smaller DNA molecule. A reverse primer R1 can have a first portion complementary to an ending sequence of region A and can have a second portion having an overlapping sequence. A forward primer F2 can have a first portion complementary to a starting sequence of region B, where the forward primer includes a complementary overlapping sequence (e.g., the same first portion or a second portion) that is complementary to the overlapping sequence. The first portion of F2 may be the entire primer. The smaller DNA molecules can be used to determine haplotypes of regions. Kits including the particular forward and reverse primers are also described.
Systems and methods for using determination of base modification in analyzing nucleic acid molecules and acquiring data for analysis of nucleic acid molecules are described herein. Base modifications may include methylations. Methods to determine base modifications may include using features derived from sequencing. These features may include the pulse width of an optical signal from sequencing bases, the interpulse duration of bases, and the identity of the bases. Machine learning models can be trained to detect the base modifications using these features. The relative modification or methylation levels between haplotypes may indicate a disorder. Modification or methylation statuses may also be used to detect chimeric molecules.
Various embodiments are directed to detecting infection-causing microbial cell-free DNA from a biological sample based on their size profiles and/or end signatures, in which the detection of infection-causing microbial DNA can be performed without no template control (NTC) samples. Embodiments can include identifying the infection-causing pathogen-derived microbial DNA based on sizes of microbial cell-free DNA molecules. Embodiments can also include identifying from the infection-causing pathogen-derived microbial DNA based on end signatures of microbial cell-free DNA molecules. Embodiments can also include applying a machine-learning algorithm to a plurality of vectors that represent end signatures of the microbial cell-free DNA molecules, to identify the infection-causing pathogen-derived microbial DNA. By detecting the infection-causing pathogen-derived microbial DNA, a level of infection for the biological sample can be predicted.
Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The percentage of fetal DNA can be calculated from the same or different data used to determine the cutoff value, and can use a locus where the mother is homozygous and the fetus is heterozygous. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT).
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
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
Systems and methods for using determination of base modification in analyzing nucleic acid molecules and acquiring data for analysis of nucleic acid molecules are described herein. Base modifications may include methylations. Methods to determine base modifications may include using features derived from sequencing. These features may include the pulse width of an optical signal from sequencing bases, the interpulse duration of bases, and the identity of the bases. Machine learning models can be trained to detect the base modifications using these features. The relative modification or methylation levels between haplotypes may indicate a disorder. Modification or methylation statuses may also be used to detect chimeric molecules.
Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 25/00 - ICT specially adapted for hybridisationICT 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 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
21.
DIAGNOSTIC APPLICATIONS USING NUCLEIC ACID FRAGMENTS
Various embodiments are directed to applications (e.g., classification of biological samples) of the analysis of the count, the fragmentation patterns, and size of cell-free nucleic acids, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, such as viruses. Embodiments of one application can determine if a subject has a particular condition. For example, a method of present disclosure can determine if a subject has cancer or a tumor, or other pathology. Embodiments of another application can be used to assess the stage of a condition, or the progression of a condition over time. For example, a method of the present disclosure may be used to determine a stage of cancer in a subject, or the progression of cancer in a subject over time (e.g., using samples obtained from a subject at different times).
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 1/6879 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for sex determination
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
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
Methods are provided to improve the positive predictive value for cancer detection using cell-free nucleic acid samples. Various embodiments are directed to applications (e.g., diagnostic applications) of the analysis of the fragmentation patterns and size of cell-free DNA, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, including viruses. Embodiments of one application can determine if a subject has a particular condition. For example, a method of present disclosure can determine if a subject has cancer or a tumor, or other pathology. Embodiments of another application can be used to assess the stage of a condition, or the progression of a condition over time. For example, a method of the present disclosure may be used to determine a stage of cancer in a subject, or the progression of cancer in a subject over time (e.g., using samples obtained from a subject at different times).
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
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
Various embodiments are directed to applications (e.g., classification of biological samples) of the analysis of the count and size of cell-free nucleic acids, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, such as viruses. Embodiments of one application can predict if a subject previously treated for a pathology will relapse at a future time point. Targeted sequencing (e.g., specifically designed capture probes, amplification primers) can be used to identify DNA across the entire viral genome.
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
Temporal variations in one or more characteristics measured from a cell-free DNA sample are used to estimate a gestational age of a fetus. Example characteristics include the methylation level measured from the cell-free DNA sample, size of DNA fragments measured from the cell-free DNA sample (e.g., proportion of fetal-derived DNA fragments longer than a specified size), and ending patterns of the DNA fragments align to a reference genome.
Nuclease activity can affect the methylation level and fragmentation of cfDNA. Certain levels of nuclease activity may be correlated with certain levels of methylation in certain regions. Methylation level in certain genomic regions can be analyzed to classify nuclease activity. Methylation statuses of different genomic regions compared to methylation statuses of other genomic regions can determine a level of a condition (e.g., a disease such as cancer or disorder) in a subject. Nuclease activity can be monitored through analysis of methylation statuses of different sites. The efficacy of a treatment can also be determined using methylation levels at certain genomic regions. The number of fragments from genomic regions that are hypomethylated or hypermethylated in a reference genome can be used to provide information (e.g., fractional concentration) on the sample itself. The size distribution of extrachromosomal circular DNA can also be used to analyze a biological sample. Systems are also described.
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
26.
BASE MODIFICATION ANALYSIS USING ELECTRICAL SIGNALS
Systems and methods for determining base modifications using electrical signals and other data is described herein. Embodiments can make use of features derived from electrical signals related to sequencing, such as those acquired from using a nanopore, that are affected by the various base modifications, as well as an identity of nucleotides in a window around a target position whose methylation status is determined. Other features may include a vector of statistical values of a segment of the electrical signal corresponding to the nucleotide and a statistical value of the electrical signal in a window in a region of the nucleic acid molecule. The detected base modifications can be used for additional analysis of a biological sample.
Systems, methods, and apparatus for determining a fractional concentration of fetal DNA in a biological sample are provided. The biological sample may be enriched for nucleic acid molecules in a target region. A plurality of nucleic acid molecules from the enriched biological sample may be sequenced specific to the target region. One or more first loci may be determined. The fetal genome is heterozygous at each first loci such that the fetal genome has a respective first and second allele at that first loci. The maternal genome is homozygous at each first loci such that the maternal genome. For at least one of the first loci, a first number of counts of the respective first allele and a second number of counts of the respective second allele may be determined. The fractional concentration may be determined based on the first and second numbers.
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 biostatisticsICT 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
Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g., to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.
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
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
Methods and systems described herein involve using long cell-free DNA fragments to analyze a biological sample from a pregnant subject. The status of methylated CpG sites and single nucleotide polymorphisms (SNPs) is often used to analyze DNA fragments of a biological sample. A CpG site and a SNP are typically separated from the nearest CpG site or SNP by hundreds or thousands of base pairs. Finding two or more consecutive CpG sites or SNPs on most cell-free DNA fragments is improbable or impossible. Cell-free DNA fragments longer than 600 bp may include multiple CpG sites and/or SNPs. The presence of multiple CpG sites and/or SNPs on long cell-free DNA fragments may allow for analysis than with short cell-free DNA fragments alone. The long cell-free DNA fragments can be used to identify a tissue of origin and/or to provide information on a fetus in a pregnant female.
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
30.
NON-INVASIVE DETERMINATION OF TISSUE SOURCE OF CELL-FREE DNA
Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.
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
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
Embodiments may include a method of sequencing cell-free DNA fragments. Cell-free DNA fragments may include plasma DNA fragments. The method may include receiving a biological sample including a plurality of DNA fragments. The biological sample may have a first concentration of DNA fragments. The method may also include concentrating the biological sample to have a second concentration of DNA fragments. The second concentration of DNA fragments may be 5 or more times higher than the first concentration of DNA fragments. The method may further include passing the plurality of DNA fragments through nanopores on a substrate. For each of the plurality of DNA fragments, electrical signals may be detected as the DNA fragment passes through a nanopore. The electrical signals may correspond to the sequence of the DNA fragment. Systems for analyzing DNA fragments are also described.
The ends of cell-free DNA fragments may be used for analysis of a biological sample. In some embodiments, DNA from a urine sample may be analyzed. Cell-free DNA fragments often include jagged ends, where one end of one strand of double-stranded DNA extends beyond the other end of the other strand. The length and amount of these jagged ends may be used to determine a level of a condition of an individual. The density of ends of fragments in certain regions may also be used in classifying the level of a condition. Additionally, DNA fragments may show a periodic pattern with the amount of DNA fragments corresponding to a length of the overhang. The periodicity may be analyzed to determine properties of a biological sample. Jagged ends may also be analyzed with a technique that avoids trimming overhanging 3′ ends of a double-stranded 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
C12Q 1/6816 - Hybridisation assays characterised by the detection means
Embodiments are related to the accurate detection of somatic mutations in the plasma (or other samples containing cell-free DNA) of cancer patients and for subjects being screened for cancer. The detection of these molecular markers would be useful for the screening, detection, monitoring, management, and prognostication of cancer patients. For example, a mutational load can be determined from the identified somatic mutations, and the mutational load can be used to screen for any or various types of cancers, where no prior knowledge about a tumor or possible cancer of the subject may be required. Embodiments can be useful for guiding the use of therapies (e.g. targeted therapy, immunotherapy, genome editing, surgery, chemotherapy, embolization therapy, anti-angiogenesis therapy) for cancers. Embodiments are also directed to identifying de novo mutations in a fetus by analyzing a maternal sample having cell-free DNA from the fetus.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
An amount of mitochondrial DNA molecules relative to an amount of nuclear DNA molecules is determined in a biological sample, and the relative amount is used for various purposes, e.g., screening, detection, prognostication or monitoring of various physiological and pathological conditions. As examples, an amount of mitochondrial DNA can be used to estimate a concentration of DNA of a tissue type, such as a fetal DNA concentration, tumor DNA concentration, or a concentration of DNA in the biological sample derived from a non-hematopoietic tissue source. Sequencing techniques can be used to determine a mitochondrial DNA concentration in a sample for an accurate detection of a level of cancer. A level of an auto-immune disease is also determined using a relative amount of mitochondrial DNA molecules compared nuclear DNA molecules.
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
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
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
A fractional concentration of fetal relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments of a particular size or range of sizes. DNA fragments may be sequenced to obtain sequence reads, and the sequence reads may be aligned to a reference genome to determine sizes of the DNA fragments. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a parameter providing a statistical measure of a size profile and the fractional concentration of the fetal DNA. For a given sample, a value of the parameter can be determined from DNA fragments of a particular size or range of sizes in a sample. A comparison of the value to the calibration data points can provide the estimate of the fractional concentration of the fetal DNA.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6816 - Hybridisation assays characterised by the detection means
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
Size-band analysis is used to determine whether a chromosomal region exhibits a copy number aberration or an epigenetic alteration. Multiple size ranges may be analyzed instead of focusing on specific sizes. By using multiple size ranges instead of specific sizes, methods may analyze more sequence reads and may be able to determine whether a chromosomal region exhibits a copy number aberration even when clinically-relevant DNA may be a low fraction of the biological sample. Using multiple ranges may allow for the use of all sequence reads from a genomic region, rather than a selected subset of reads in the genomic region. The accuracy of analysis may be increased with higher sensitivity at similar or higher specificity. Analysis may include fewer sequencing reads to achieve the same accuracy, resulting in a more efficient process.
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 1/6809 - Methods for determination or identification of nucleic acids involving differential 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
37.
NUCLEASE-ASSOCIATED END SIGNATURE ANALYSIS FOR CELL-FREE NUCLEIC ACIDS
Various embodiments are directed to using nuclease expression in tissues that influences cell-free DNA end signatures/motifs and size of overhang between DNA strands. Embodiments can identify a nuclease that is being differentially regulated in abnormal cells relative to normal cells. Embodiments can determine that the nuclease preferentially cuts DNA into DNA molecules having: (i) a particular sequence end signature; or (ii) a specified length of overhang between a first strand and a second strand. A parameter can be determined for a biological sample based on an amount of DNA molecules that include an end sequence corresponding to the particular sequence end signature and/or a measured property correlating to the specified length of overhang. The parameter can be used to determine a characteristic of a tissue type, a fractional concentration of clinically-relevant DNA molecules, or a level of abnormality of a tissue type in the biological sample.
C12Q 1/34 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase
Systems and methods for using determination of base modification in analyzing nucleic acid molecules and acquiring data for analysis of nucleic acid molecules are described herein. Base modifications may include methylations. Methods to determine base modifications may include using features derived from sequencing. These features may include the pulse width of an optical signal from sequencing bases, the interpulse duration of bases, and the identity of the bases. Machine learning models can be trained to detect the base modifications using these features. The relative modification or methylation levels between haplotypes may indicate a disorder. Modification or methylation statuses may also be used to detect chimeric molecules.
Methods and systems described herein involve using long cell-free DNA fragments to analyze a biological sample from a pregnant subject. The status of methylated CpG sites and single nucleotide polymorphisms (SNPs) is often used to analyze DNA fragments of a biological sample. A CpG site and a SNP are typically separated from the nearest CpG site or SNP by hundreds or thousands of base pairs. Finding two or more consecutive CpG sites or SNPs on most cell-free DNA fragments is improbable or impossible. Cell-free DNA fragments longer than 600 bp may include multiple CpG sites and/or SNPs. The presence of multiple CpG sites and/or SNPs on long cell-free DNA fragments may allow for analysis than with short cell-free DNA fragments alone. The long cell-free DNA fragments can be used to identify a tissue of origin and/or to provide information on a fetus in a pregnant female.
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
40.
SIZE-BASED ANALYSIS OF CELL-FREE TUMOR DNA FOR CLASSIFYING LEVEL OF CANCER
A fractional concentration of tumor DNA in a plasma sample is estimated by analyzing a biological sample of an organism. One or more sequence reads obtained from a sequencing of the DNA fragment are received. The one or more sequence reads are aligned to a reference genome to obtain aligned locations for both ends of the DNA fragment. Using the aligned locations, a size of the DNA fragment is determined. For each size of a plurality of sizes, an amount of a set of the plurality of DNA fragments from the plasma sample corresponding to the size is determined. A first value of a first parameter is calculated based on the amounts of DNA fragments at multiple sizes. The first value is compared to a calibration value. A fractional concentration of tumor DNA in the plasma sample is estimated based on the comparison.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
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
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6816 - Hybridisation assays characterised by the detection means
41.
Molecular analyses using long cell-free fragments in pregnancy
Methods and systems described herein involve using long cell-free DNA fragments to analyze a biological sample from a pregnant subject. The status of methylated CpG sites and single nucleotide polymorphisms (SNPs) is often used to analyze DNA fragments of a biological sample. A CpG site and a SNP are typically separated from the nearest CpG site or SNP by hundreds or thousands of base pairs. Finding two or more consecutive CpG sites or SNPs on most cell-free DNA fragments is improbable or impossible. Cell-free DNA fragments longer than 600 bp may include multiple CpG sites and/or SNPs. The presence of multiple CpG sites and/or SNPs on long cell-free DNA fragments may allow for analysis than with short cell-free DNA fragments alone. The long cell-free DNA fragments can be used to identify a tissue of origin and/or to provide information on a fetus in a pregnant female.
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
42.
BITERMINAL DNA FRAGMENT TYPES IN CELL-FREE SAMPLES AND USES THEREOF
The present disclosure describes techniques for measuring quantities (e.g., relative frequencies) of end motif pairs of cell-free DNA fragments in a biological sample of an organism for measuring a property of the sample (e.g., fractional concentration of clinically-relevant DNA) and/or determining a pathology of the organism based on such measurements. Different tissue types exhibit different patterns for the relative frequencies of the end motif pairs. The present disclosure provides various uses for measurements of the relative frequencies of end motif pairs of cell-free DNA, e.g., in mixtures of cell-free DNA from various tissues. DNA from certain tissue(s) may be referred to as clinically-relevant DNA.
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
43.
Method for a photon induced material deposition and a device therefor
A method for photon induced material deposition includes providing a first solution, which contains metallate or metal ions, providing a second solution, which contains light sensitive reducing agent, such as semiconductor nanoparticles, mixing the first solution and the second solution to form a reagent on a substrate, and focusing a light source on the reagent to form a mechanically rigid deposition in the focus of the light source.
B29C 64/135 - Processes of additive manufacturing using only liquids or viscous materials, e.g. depositing a continuous bead of viscous material using layers of liquid which are selectively solidified characterised by the energy source therefor, e.g. by global irradiation combined with a mask the energy source being concentrated, e.g. scanning lasers or focused light sources
B33Y 30/00 - Apparatus for additive manufacturingDetails thereof or accessories therefor
B33Y 80/00 - Products made by additive manufacturing
B29C 64/273 - Arrangements for irradiation using laser beamsArrangements for irradiation using electron beams [EB] pulsedArrangements for irradiation using laser beamsArrangements for irradiation using electron beams [EB] frequency modulated
H01L 21/02 - Manufacture or treatment of semiconductor devices or of parts thereof
Various methods, apparatuses, and systems are provided for detecting a genetic disorder in a gene associated with a nuclease, for determining an efficacy of a dosage of an anticoagulant, and for monitoring an activity of a nuclease. Measured parameter values can be compared to a reference value to determine classifications of a genetic disorder, efficiency, or activity. An amount of a particular base (e.g., in an end motif) at fragment ends, an amount of a particular base at fragment ends of a particular size, or a total amount of cell-free DNA fragments (e.g., as a concentration) can be used. Certain samples may be treated with an anticoagulant, and different incubation times can be used for certain methods.
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 apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
Methods, systems, and apparatus are provided for determining zygosity of a multiple-fetus pregnancy using a biological sample taken from the mother. The fetal and maternal DNA in the sample (e.g. plasma) can be analyzed for a particular chromosomal region to identify genetic differences in the fetuses. For example, a normalized parameter for the measure of a primary or secondary allele can show variances for different chromosomal regions when fetuses are dizygotic. Such a variance can be determined relative to an expected value if the fetuses were genetically identical. Statistical methods are provided for analyzing the variation of the normalized parameters to determine fetal DNA concentration and the maternal-fetal mixed genotype at various loci. Parental genotype and haplotype information can also be used to identify inheritance of different parental haplotypes to indicate genetic differences among the fetuses.
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 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
47.
Determination of base modifications of nucleic acids
Systems and methods for using determination of base modification in analyzing nucleic acid molecules and acquiring data for analysis of nucleic acid molecules are described herein. Base modifications may include methylations. Methods to determine base modifications may include using features derived from sequencing. These features may include the pulse width of an optical signal from sequencing bases, the interpulse duration of bases, and the identity of the bases. Machine learning models can be trained to detect the base modifications using these features. The relative modification or methylation levels between haplotypes may indicate a disorder. Modification or methylation statuses may also be used to detect chimeric molecules.
Techniques are provided for analyzing circular DNA in a biological sample (e.g., including cell-free DNA, such as plasma). For example, to measure circular DNA, cleaving can be performed to linearize the circular DNA so that they may be sequenced. Example cleaving techniques include restriction enzymes and transposases. Then, one or more criteria can be used to identify linearized DNA molecules, e.g., so as to differentiate from linear DNA molecules. An example criterion is mapping a pair of reversed end sequences to a reference genome. Another example criterion is identification of a cutting tag, e.g., associated with a restriction enzyme or an adapter sequence added by a transposase. Once circular DNA molecules (e.g., eccDNA and circular mitochondrial DNA) are identified, they may be analyzed (e.g., to determine a count, size profile, and/or methylation) to measure a property of the biological sample, including genetic properties and level of a disease.
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
Techniques are provided for detecting hematological disorders using cell-free DNA in a blood sample, e.g., using plasma or serum. For example, an assay can target one or more differentially-methylated regions specific to a particular hematological cell lineage (e.g., erythroblasts). A methylation level can be quantified from the assay to determine an amount of methylated or unmethylated DNA fragments in a cell-free mixture of the blood sample. The methylation level can be compared to one or more cutoff values, e.g., that correspond to a normal range for the particular hematological cell lineage as part of determining a level of a hematological disorder.
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential 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
C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
Particular forward and reverse primers may be used to link distant regions of the same large DNA molecule into a smaller DNA molecule. A reverse primer R1 can have a first portion complementary to an ending sequence of region A and can have a second portion having an overlapping sequence. A forward primer F2 can have a first portion complementary to a starting sequence of region B, where the forward primer includes a complementary overlapping sequence (e.g., the same first portion or a second portion) that is complementary to the overlapping sequence. The first portion of F2 may be the entire primer. The smaller DNA molecules can be used to determine haplotypes of regions. Kits including the particular forward and reverse primers are also described.
Cell-free DNA molecules in a mixture of a biological sample can be analyzed to detect viral DNA. Methylation of viral DNA molecules at one or more sites in the viral genome can be determined. Mixture methylation level(s) can be measured based on one or more amounts of the plurality of cell-free DNA molecules methylated at a set of site(s) of the particular viral genome. The mixture methylation level(s) can be determined in various ways, e.g., as a density of cell-free DNA molecules that are methylated at a site or across multiple sites or regions. The mixture methylation level(s) can be compared to reference methylation level(s), e.g., determined from at least two cohorts of other subjects. The cohorts can have different classifications (including the first condition) associated with the particular viral genome. A first classification of whether the subject has the first condition can be determined based on the comparing.
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 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
53.
Size-based sequencing analysis of cell-free tumor DNA for classifying level of cancer
A classification of a level of cancer in an organism is determined by analyzing a biological sample of the organism. The biological sample comprises clinically-relevant DNA and other DNA. At least some of the DNA is cell-free in the biological sample. An amount of a first set of DNA fragments from the biological sample corresponding to each of a plurality of sizes is measured. A first value of a first parameter is calculated based on the amounts of DNA fragments at the plurality of sizes. The first value is compared to a reference value. A classification of a level of cancer in the organism is determined based on the comparison.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
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
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6816 - Hybridisation assays characterised by the detection means
54.
Diagnostic applications using nucleic acid fragments
Various embodiments are directed to applications (e.g., classification of biological samples) of the analysis of the count, the fragmentation patterns, and size of cell-free nucleic acids, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, such as viruses. Embodiments of one application can determine if a subject has a particular condition. For example, a method of present disclosure can determine if a subject has cancer or a tumor, or other pathology. Embodiments of another application can be used to assess the stage of a condition, or the progression of a condition over time. For example, a method of the present disclosure may be used to determine a stage of cancer in a subject, or the progression of cancer in a subject over time (e.g., using samples obtained from a subject at different times).
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 1/6879 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for sex determination
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
55.
METHYLATION PATTERN ANALYSIS OF HAPLOTYPES IN TISSUES IN A DNA MIXTURE
Systems, apparatuses, and method are provided for determining the contributions of different tissues to a biological sample that includes a mixture of cell-free DNA molecules from various tissues types, e.g., as occurs in plasma or serum and other body fluids. Embodiments can analyze the methylation patterns of the DNA mixture (e.g., methylation levels at particular loci) for a particular haplotype and determine fractional contributions of various tissue types to the DNA mixture, e.g., of fetal tissue types or tissue types of specific organs that might have a tumor. Such fractional contributions determined for a haplotype can be used in a variety of ways.
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 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
The present disclosure describes techniques for measuring quantities (e.g., relative frequencies) of sequence end motifs of cell-free DNA fragments in a biological sample of an organism for measuring a property of the sample (e.g., fractional concentration of clinically-relevant DNA) and/or determining a condition of the organism based on such measurements. Different tissue types exhibit different patterns for the relative frequencies of the sequence end motifs. The present disclosure provides various uses for measures of the relative frequencies of sequence end motifs of cell-free DNA, e.g., in mixtures of cell-free DNA from various tissues. DNA from one of such tissue may be referred to as clinically-relevant DNA.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
The present disclosure relates to arginase albumin binding domain (ABD) fusion proteins and methods of preparation and use thereof. Also provided are methods involving arginine depletion for the treatment of obesity, metabolic disorders, and related complications and comorbidities.
Disclosed herein are methods, systems, and apparatus for detecting microamplifications or microdeletions in the genome of a fetus. In some embodiments, the method comprises receiving sequence tags for each of a plurality of DNA fragments in a biological sample; determining genomic positions for the sequence tags; determining whether the density of DNA in each of a plurality of genomic regions is aberrantly high or low; identifying as a microamplification a set of consecutive genomic regions having aberrantly high density; and identifying as a microdeletion a set of consecutive genomic regions having aberrantly low density. The biological sample may be a blood sample obtained noninvasively from a female subject pregnant with the fetus.
The quality of cell-free DNA for analysis is improved by techniques described herein. Cell-free DNA may include DNA with defects that do not allow for analysis of those DNA with techniques such as sequencing and targeted capture enrichment. These defects may be defects within the strands of the DNA and not present at the ends of the DNA. These intrastrand defects in cell-free DNA can be repaired. The repair of the defects in cell-free DNA may then allow for these repaired cell-free DNA to be analyzed by techniques, including sequencing and targeted capture enrichment.
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
60.
System and method for separation of water and fat signals during spin-lock magnetic resonance imaging
Separation of fat and water signals in MRI images can be achieved by a technique that includes using a spin-lock RF pulse sequence that incorporates adiabatic pulses and using Dixon methods for water/fat separation. The spin-lock RF pulse sequence can be, for example, an adiabatic continuous-wave constant-amplitude spin-lock (ACCSL) pulse sequence. Data acquisition can use any acquisition method compatible with Dixon methods. Following data acquisition, a source image can be generated and analyzed (e.g., using Dixon methods) to generate separate water and fat images. A spatial distribution of a spin-lock based imaging biomarker (e.g., T1rho) can be determined from the water image and/or the fat image.
Whether a fetus has an aneuploidy associated with a first chromosome is detected using ratios of alleles detected in a maternal sample having a mixture of maternal and fetal DNA. DNA from the sample is enriched for target regions associated with polymorphic loci and then sequenced. Polymorphic loci (e.g., single nucleotide polymorphisms) in the target regions with fetal-specific alleles are identified on a first chromosome and on one or more reference chromosomes. A first ratio of the fetal-specific alleles and shared alleles is determined for the loci on the first chromosome. A second ratio of the fetal-specific alleles and shared alleles is determined for the loci on the reference chromosome(s). A third ratio of the first and second ratio can be compared to a cutoff to determine whether an aneuploidy is present, and whether the aneuploidy is maternally-derived or paternally-derived.
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 hybridisationICT specially adapted for gene or protein expression
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 20/40 - Population geneticsLinkage disequilibrium
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
62.
Determining a nucleic acid sequence imbalance associated with cancer using multiple markers
Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The percentage of fetal DNA can be calculated from the same or different data used to determine the cutoff value, and can use a locus where the mother is homozygous and the fetus is heterozygous. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT).
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
Cell-free DNA fragments often include jagged ends, where one end of one strand of double-stranded DNA extends beyond the other end of the other strand. The length and amount of these jagged ends may be used to determine a level of a condition of an individual, a fractional concentration of clinically-relevant DNA in a biological sample, an age of individual, or a tissue type exhibiting cancer. The jagged end length and amount may be determined using various techniques described 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
Radio frequency antennas sharing a ground plane are largely decoupled using one or more lumped capacitive elements set into holes within the ground plane. The holes, which are precisely placed, can extend to a side of the ground plane. A stub extends from a fringe of the hole either straight or bending in an L shape, and a capacitor connects between an end of the stub and another side of the hole. Capacitive elements can also be supported on raised solder pads above a ground plane or off to one side of the ground plane. Methods for manufacturing the decoupling apparatus are described.
H01Q 1/24 - SupportsMounting means by structural association with other equipment or articles with receiving set
H01Q 21/08 - Arrays of individually energised antenna units similarly polarised and spaced apart the units being spaced along, or adjacent to, a rectilinear path
65.
Accurate deduction of fetal DNA fraction with shallow-depth sequencing of maternal plasma
Embodiments of the present invention provide methods, systems, and apparatus for deducing the fetal DNA fraction in maternal plasma without using paternal or fetal genotypes. Maternal genotype information may be obtained from a maternal-only DNA sample or may be assumed from shallow-depth sequencing of a biological sample having both maternal and fetal DNA molecules. Because sequencing may be at shallow depths, a locus may have only few reads and may fail to exhibit a non-maternal allele even if a non-maternal allele is present. However, normalized parameters that characterize non-maternal alleles sequenced can be used to provide an accurate estimate of the fetal DNA fraction, even if the amount of non-maternal alleles is in error. Methods described herein may not need high-depth sequencing or enrichment of specific regions. As a result, these methods can be integrated into widely used non-invasive prenatal testing and other diagnostics.
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
Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 25/00 - ICT specially adapted for hybridisationICT 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 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
67.
Analysis of fragmentation patterns of cell-free DNA
Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 25/00 - ICT specially adapted for hybridisationICT 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 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
68.
Analysis of fragmentation patterns of cell-free DNA
Factors affecting the fragmentation pattern of cell-free DNA (e.g., plasma DNA) and the applications, including those in molecular diagnostics, of the analysis of cell-free DNA fragmentation patterns are described. Various applications can use a property of a fragmentation pattern to determine a proportional contribution of a particular tissue type, to determine a genotype of a particular tissue type (e.g., fetal tissue in a maternal sample or tumor tissue in a sample from a cancer patient), and/or to identify preferred ending positions for a particular tissue type, which may then be used to determine a proportional contribution of a particular tissue type.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 25/00 - ICT specially adapted for hybridisationICT 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 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
69.
System and method for peer-to-peer wireless communication
Methods and systems for peer-to-peer communication are provided. In one example, a first device may receive, from a server, a pairing code and a first handshake code. The first device may transmit at least a first portion of the pairing code in a first broadcast message and receive, from the second device, a second broadcast message. The first device may authenticate the second device based on at least a second portion of the pairing code in the second broadcast message. The first device may establish a wireless peer-to-peer communication channel with the second device, and receive, from the second device, a second handshake code via the wireless peer-to-peer communication channel. The first device may authorize the second party to engage in an offline interaction with the first party based on the first handshake code and the second handshake code.
Systems and methods for de-identification of medical images can be applied to medical images acquired using various techniques. A 3D medical image can be analyzed to generate an image mask that partitions the image into a foreground region and a background region. From the image mask, a “skin surface” can be reconstructed based on the boundary between the foreground region and the background region. The image mask can be modified, e.g., by moving a randomly-selected subset of the voxels from the foreground region to the background region so that the shape of the skin surface is altered, thus obscuring patient-identifying features. The original medical image can be modified by changing the intensity of voxels in the background region while preserving the original intensity of voxels in the foreground region.
G06T 5/20 - Image enhancement or restoration using local operators
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
Various applications can use fragmentation patterns related of cell-free DNA, e.g., plasma DNA and serum DNA. For example, the end positions of DNA fragments can be used for various applications. The fragmentation patterns of short and long DNA molecules can be associated with different preferred DNA end positions, referred to as size-tagged preferred ends. In another example, the fragmentation patterns relating to tissue-specific open chromatin regions were analyzed. A classification of a proportional contribution of a particular tissue type can be determined in a mixture of cell-free DNA from different tissue types. Additionally, a property of a particular tissue type can be determined, e.g., whether a sequence imbalance exists in a particular region for a tissue type or whether a pathology exists for the tissue type.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
Optimizations are provided for segmenting tissue objects included in an ultrasound image. Initially, raw pixel data is received. Here, each pixel corresponds to ultrasound information. This raw pixel data is processed through a first fully convolutional network to generate a first segmentation label map. This first map includes a first set of objects that have been segmented into a coarse segmentation class. Then, this first map is processed through a second fully convolutional network to generate a second segmentation label map. This second map is processed using the raw pixel data as a base reference. Further, this second map includes a second set of objects that have been segmented into a fine segmentation class. Then, a contour optimization algorithm is applied to at least one of the second set of objects in order to refine that object's contour boundary. Subsequently, that object is identified as corresponding to a lymph node.
Analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for solid tumor assessment or cancer screening. However, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. Regarding the size profile of plasma DNA molecules, some studies reported increased integrity of tumor-derived plasma DNA while others reported shorter tumor-derived plasma DNA molecules. We performed an analysis of the size profiles of plasma DNA in patients with cancer using massively parallel sequencing at single base resolution and in a genomewide manner. Tumor-derived plasma DNA molecules were further identified using chromosome arm-level z-score analysis (CAZA). We showed that populations of aberrantly short and long DNA molecules co-existed in the plasma of patients with cancer. The short ones preferentially carried the tumor-associated copy number aberrations. These results show the ability to use plasma DNA as a molecular diagnostic tool.
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 40/00 - ICT specially adapted for biostatisticsICT 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
74.
SEQUENCE VARIANT ANALYSIS OF CELL-FREE DNA FOR CANCER SCREENING
A frequency of somatic mutations in a biological sample (e.g., plasma or serum) of a subject undergoing screening or monitoring for cancer, can be compared with that in the constitutional DNA of the same subject. A parameter can derived from these frequencies and used to determine a classification of a level of cancer. False positives can be filtered out by requiring any variant locus to have at least a specified number of variant sequence reads (tags), thereby providing a more accurate parameter. The relative frequencies for different variant loci can be analyzed to determine a level of heterogeneity of tumors in a patient.
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 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
An aberration in a fetal genome can be identified by analyzing a sample of fetal and maternal DNA. Classifications of whether an aberration (amplification or deletion) exists in a subchromosomal region are determined using count-based and size-based methods. The count classification and the size classification can be used in combination to determine whether only the fetus or only the mother, or both, have the aberration in the subchromosomal region, thereby avoiding false positives when the mother has the aberration and the fetus does not.
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
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
76.
Non-invasive determination of methylome of tumor from plasma
Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
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
Methods are provided for diagnosing pregnancy-associated disorders, determining allelic ratios, determining maternal or fetal contributions to circulating transcripts, and/or identifying maternal or fetal markers using a sample from a pregnant female subject. Also provided is use of a gene for diagnosing a pregnancy-associated disorder in a pregnant female subject.
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
Methods and systems for operating a sensor network are provided. In one example, a server may provide graphical data representing a hierarchical sensor network for displaying at a client device. The server may receive a selection to display sensor data from a first node of the nodes of the hierarchical sensor network and determine, based on the selection, a hierarchical sensor label associated with one or more first sensors of the hierarchical sensor network corresponding to the first node. The server may also receive a plurality of messages including sensor data generated by a plurality of sensors of the hierarchical sensor network from an in-bound real-time message processor, and identify a first set of messages based on the hierarchical sensor label. The server may extract the sensor data from the first set of messages and provide the sensor data for displaying at the client device.
H04L 29/08 - Transmission control procedure, e.g. data link level control procedure
G06K 7/10 - Methods or arrangements for sensing record carriers by electromagnetic radiation, e.g. optical sensingMethods or arrangements for sensing record carriers by corpuscular radiation
H04L 29/06 - Communication control; Communication processing characterised by a protocol
H04L 12/24 - Arrangements for maintenance or administration
Embodiments are related to the accurate detection of somatic mutations in the plasma (or other samples containing cell-free DNA) of cancer patients and for subjects being screened for cancer. The detection of these molecular markers would be useful for the screening, detection, monitoring, management, and prognostication of cancer patients. For example, a mutational load can be determined from the identified somatic mutations, and the mutational load can be used to screen for any or various types of cancers, where no prior knowledge about a tumor or possible cancer of the subject may be required. Embodiments can be useful for guiding the use of therapies (e.g. targeted therapy, immunotherapy, genome editing, surgery, chemotherapy, embolization therapy, anti-angiogenesis therapy) for cancers. Embodiments are also directed to identifying de novo mutations in a fetus by analyzing a maternal sample having cell-free DNA from the fetus.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The percentage of fetal DNA can be calculated from the same or different data used to determine the cutoff value, and can use a locus where the mother is homozygous and the fetus is heterozygous. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (SPRT).
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
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
Size-band analysis is used to determine whether a chromosomal region exhibits a copy number aberration or an epigenetic alteration. Multiple size ranges may be analyzed instead of focusing on specific sizes. By using multiple size ranges instead of specific sizes, methods may analyze more sequence reads and may be able to determine whether a chromosomal region exhibits a copy number aberration even when clinically-relevant DNA may be a low fraction of the biological sample. Using multiple ranges may allow for the use of all sequence reads from a genomic region, rather than a selected subset of reads in the genomic region. The accuracy of analysis may be increased with higher sensitivity at similar or higher specificity. Analysis may include fewer sequencing reads to achieve the same accuracy, resulting in a more efficient process.
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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
82.
Methylation pattern analysis of tissues in a DNA mixture
The contributions of different tissues to a DNA mixture are determined using methylation levels at particular genomic sites. Tissue-specific methylation levels of M tissue types can be used to deconvolve mixture methylation levels measured in the DNA mixture, to determine fraction contributions of each of the M tissue types. Various types of genomic sites can be chosen to have particular properties across tissue types and across individuals, so as to provide increased accuracy in determining contributions of the various tissue types. The fractional contributions can be used to detect abnormal contributions of a particular tissue, indicating a disease state for the tissue. A differential in fractional contributions for different sizes of DNA fragments can also be used to identify a diseased state of a particular tissue. A sequence imbalance for a particular chromosomal region can be detected in a particular tissue, e.g., identifying a location of a tumor.
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
Cell-free DNA molecules in a mixture of a biological sample can be analyzed to detect viral DNA. Methylation of viral DNA molecules at one or more sites in the viral genome can be determined. Mixture methylation level(s) can be measured based on one or more amounts of the plurality of cell-free DNA molecules methylated at a set of site(s) of the particular viral genome. The mixture methylation level(s) can be determined in various ways, e.g., as a density of cell-free DNA molecules that are methylated at a site or across multiple sites or regions. The mixture methylation level(s) can be compared to reference methylation level(s), e.g., determined from at least two cohorts of other subjects. The cohorts can have different classifications (including the first condition) associated with the particular viral genome. A first classification of whether the subject has the first condition can be determined based on the comparing.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
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
84.
Tumor suppressor REC8 as a biomarker for gastric cancer
The present invention provides a method for diagnosing and determining prognosis of gastric cancer in a subject by detecting suppressed expression of the REC8 gene, which in some cases is due to elevated methylation level in the genomic sequence of this gene. A kit and device useful for such a method are also provided. In addition, the present invention provides a method for treating gastric cancer by increasing REC8 gene expression or activity. Lastly, a highly sensitive and accurate detection method is provided for rapid determination of REC8 gene methylation status.
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
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
85.
Identifying a de novo fetal mutation from a maternal biological sample
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 biostatisticsICT 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
Methods are provided to improve the positive predictive value for cancer detection using cell-free nucleic acid samples. Various embodiments are directed to applications (e.g., diagnostic applications) of the analysis of the fragmentation patterns and size of cell-free DNA, e.g., plasma DNA and serum DNA, including nucleic acids from pathogens, including viruses. Embodiments of one application can determine if a subject has a particular condition. For example, a method of present disclosure can determine if a subject has cancer or a tumor, or other pathology. Embodiments of another application can be used to assess the stage of a condition, or the progression of a condition over time. For example, a method of the present disclosure may be used to determine a stage of cancer in a subject, or the progression of cancer in a subject over time (e.g., using samples obtained from a subject at different times).
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.
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
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
Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
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
89.
SEQUENCE VARIANT ANALYSIS OF CELL-FREE DNA FOR CANCER SCREENING
A frequency of somatic mutations in a biological sample (e.g., plasma or serum) of a subject undergoing screening or monitoring for cancer, can be compared with that in the constitutional DNA of the same subject. A parameter can derived from these frequencies and used to determine a classification of a level of cancer. False positives can be filtered out by requiring any variant locus to have at least a specified number of variant sequence reads (tags), thereby providing a more accurate parameter. The relative frequencies for different variant loci can be analyzed to determine a level of heterogeneity of tumors in a patient.
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
B01J 19/00 - Chemical, physical or physico-chemical processes in generalTheir relevant apparatus
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
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
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
90.
Size-based analysis of fetal DNA fraction in plasma
A fractional concentration of clinically-relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments at multiple sizes. For example, the fractional concentration of fetal DNA in maternal plasma or tumor DNA in a patient's plasma can be determined. The size of DNA fragments in a sample is shown to be correlated with a proportion of fetal DNA and a proportion of tumor DNA, respectively. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a size parameter and the fractional concentration of the clinically-relevant DNA. For a given sample, a first value of a size parameter can be determined from the sizes of DNA fragments in a sample. A comparison of the first value to the calibration data points can provide the estimate of the fractional concentration of the clinically-relevant DNA.
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6816 - Hybridisation assays characterised by the detection means
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
Diseases (e.g., cancer) of a particular organ can be detected by analyzing cell-free DNA. Some embodiments may use an organ-associated sample that is from a particular organ or passes through the particular organ, as may occur, for example, in urine, saliva, blood, and stool samples. In some embodiments, methylation levels of cell-free DNA can be measured in a sample. Tissue-specific methylation patterns can be used to determine fractional contributions from different tissue types. In other embodiments, sizes of organ-associated cell-free DNA can be measured. A statistical measure of the size profile may indicate that cell-free DNA fragments are collectively longer than expected for subjects with healthy tissue compared to non-healthy tissue. In other embodiments, two different samples can be analyzed to determine whether a particular organ has cancer. Cell-free DNA in a blood sample and organ-associated sample can both be analyzed to identify chromosomal regions exhibiting a copy number aberration.
G01N 33/493 - Physical analysis of biological material of liquid biological material urine
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6886 - 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
92.
Gestational age assessment by methylation and size profiling of maternal plasma DNA
Temporal variations in one or more characteristics measured from a cell-free DNA sample are used to estimate a gestational age of a fetus. Example characteristics include the methylation level measured from the cell-free DNA sample, size of DNA fragments measured from the cell-free DNA sample (e.g., proportion of fetal-derived DNA fragments longer than a specified size), and ending patterns of the DNA fragments align to a reference genome.
Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.
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
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
The disclosure provides a centrifugal microfluidics control system and a method configuring the same. The system may comprise a centrifugal tube; a centrifugal unit for accommodating the centrifugal tube and providing a centrifugal force to the centrifugal tube; a control unit fixed in bottom of the centrifugal tube; and a microfluidic supporting unit coupled to the control unit in the centrifugal tube. The control unit may change an orientation of the microfluidic supporting unit to change a direction of the centrifugal force applied to the microfluidic supporting unit.
Techniques are provided for detecting hematological disorders using cell-free DNA in a blood sample, e.g., using plasma or serum. For example, an assay can target one or more differentially-methylated regions specific to a particular hematological cell lineage (e.g., erythroblasts). A methylation level can be quantified from the assay to determine an amount of methylated or unmethylated DNA fragments in a cell-free mixture of the blood sample. The methylation level can be compared to one or more cutoff values, e.g., that correspond to a normal range for the particular hematological cell lineage as part of determining a level of a hematological disorder.
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 1/6888 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
96.
Light modulator using total internal reflection at an interface with a tunable conductive layer
A light modulator (e.g., for terahertz radiation) may be constructed using a prism in which light undergoes total internal reflection (TIR) at one surface. A tunable conductive layer is disposed on the TIR surface. The tunable conductive layer can have a conductivity that is dynamically controllable, e.g., by applying a voltage across the tunable conductive layer or by optically pumping the tunable conductive layer. The tunable conductive layer can absorb a portion of the reflected light beam, attenuating the beam, with the attenuation being a function of the electrical conductivity of the tunable conductive layer. The phase of the reflected light beam can also be altered as a function of electrical conductivity of the tunable conductive layer.
H04B 10/00 - Transmission systems employing electromagnetic waves other than radio-waves, e.g. infrared, visible or ultraviolet light, or employing corpuscular radiation, e.g. quantum communication
G02B 26/08 - Optical devices or arrangements for the control of light using movable or deformable optical elements for controlling the direction of light
G01N 21/3581 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using far infrared lightInvestigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using Terahertz radiation
G02F 1/315 - Digital deflection devices based on the use of controlled total internal reflection
H01Q 15/00 - Devices for reflection, refraction, diffraction or polarisation of waves radiated from an antenna, e.g. quasi-optical devices
G02F 1/01 - Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulatingNon-linear optics for the control of the intensity, phase, polarisation or colour
97.
Prodrug of green tea epigallocatechin-3-gallate (pro-EGCG) for use in the treatment of endometriosis
Method of treating endometriosis and related indications, comprising the administration of Pro-EGCG, a synthetic and derivative product of epigallocatechin-3-gallate [(−)-EGCG]. Use of Pro-EGCG in the manufacture of a medicament for treating endometriosis and related indications. Pro-EGCG for use in the treatment of endometriosis and related indications.
A classification of a level of cancer in an organism is determined by analyzing a biological sample of the organism. The biological sample comprises clinically-relevant DNA and other DNA. At least some of the DNA is cell-free in the biological sample. An amount of a first set of DNA fragments from the biological sample corresponding to each of a plurality of sizes is measured. A first value of a first parameter is calculated based on the amounts of DNA fragments at the plurality of sizes. The first value is compared to a reference value. A classification of a level of cancer in the organism is determined based on the comparison.
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
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6816 - Hybridisation assays characterised by the detection means
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)
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
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
99.
Detecting chromosomal aberrations associated with cancer using genomic sequencing
Methods, systems, and apparatus determine whether a first chromosomal region exhibits a deletion or an amplification associated with cancer in a sample from a subject (e.g., where the sample includes a mixture of cell-free DNA from tumor cells and non-malignant cells. Nucleic acid molecules of the biological sample are sequenced. Respective amounts of a clinically-relevant chromosomal region and of background chromosomal region(s) are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether first chromosomal region exhibits a deletion or an amplification associated with cancer.
G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
100.
Determining progress of chromosomal aberrations over time
Systems, apparatus, and methods are provided for determining aberrations in a biological sample from an organism. Biological samples including cell-free DNA fragments are analyzed to identify imbalances in chromosomal regions, e.g., due to deletions and/or amplifications in a tumor. Multiple loci are used for each chromosomal region. Imbalances can be used to diagnose a patient for cancer, prognosticate a patient with cancer, or to detect the presence or monitor progress of a premalignant condition. The severity of an imbalance as well as the number of regions exhibiting an imbalance can be used. A systematic analysis of non-overlapping segments of a genome can provide a general screening tool for a sample. Additionally, a patient can be tested over time to track severity of each of one or more chromosomal regions and a number of chromosomal regions to enable screening and prognosticating, as well as monitoring of progress (e.g. after treatment).
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
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