46 results about "Variant allele" patented technology

To provide a technique that enables direct seeding cultivation of seed potatoes in the field of production of sweet potato tuberous roots (sweet potato cultivation), which offers significant labor-saving benefits, wherein the technique enables efficient development of sweet potato plants having desired traits and exhibiting low enlargement of seed potatoes.SOLUTION: A method for identifying a sweet potato plant exhibiting low enlargement of seed potatoes, includes the steps of: detecting a nucleotide site indicating the "Kyushu 199-type variant allele" associated with a DNA marker from a genomic DNA of the sweet potato plant to be identified, with respect to "the DNA marker that shows relevance to the phenotype of low enlargement of seed potatoes" in the genomic DNA of sweet potato plants; and determining that the sweet potato plant to be identified is a sweet potato plant exhibiting low enlargement of seed potatoes if a nucleotide site indicating the "Kyushu 199-type variant allele" associated with the DNA marker is detected in the detection step.SELECTED DRAWING: Figure 2

Methods, systems, and software for estimating circulating tumor fraction are provided. A first plurality of nucleic acid sequences for a plurality of loci in genomic DNA from a solid tumor sample is obtained. A second plurality of nucleic acid sequences for a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the same subject is obtained. One or more somatic mutations is identified in the first plurality of nucleic acid sequences. A variant allele frequency (VAF) is determined for each somatic mutation based on a frequency of the respective somatic mutation in the liquid biopsy sample and a frequency of the corresponding wild type allele in the liquid biopsy sample, thereby determining a set of VAFs. An estimate of the circulating tumor fraction for the test subject is determined based on the set of VAFs for the one or more somatic mutations.

The invention relates to the technical field of biomedicine, in particular to a method for constructing a plasma ctDNA organ distribution characteristic spectrum of advanced colorectal cancer. The method comprises the following steps: collecting a peripheral blood sample at multiple time points, separating plasma by adopting a double-centrifugal method, and extracting circulating tumor DNA (Deoxyribose Nucleic Acid); carrying out whole exome sequencing based on ctDNA to obtain genome variation information and calculating variation allele frequency, and synchronously detecting the expression quantity of immune-related proteins by adopting an Olink proteomics technology; integrating the genome data, the protein expression data and the clinical pathological features, and constructing a multi-dimensional feature data matrix; and taking the organ metastasis condition confirmed by iconography as a supervision label, training a model by applying a machine learning algorithm, screening key prediction factors, constructing a quantitative prediction model, and finally generating a visual organ metastasis tendency prediction map. According to the method, early and accurate prediction of the advanced colorectal cancer organ metastasis tendency is realized through multi-omics data collaborative analysis and machine learning modeling.

The disclosure relates to methods of assessing the success of treatment with durvalumab and chemotherapy for resectable non-small cell lung cancer (R-NSCLC) in patients based on circulating tumor DNA (ctDNA) detection, ctDNA clearance and / or partial clearance and / or variant allele fraction (VAF) before and after such treatment. The disclosure also relates to methods for treating patients with R-NSCLC based on ctDNA detection, ctDNA clearance and / or partial molecular clearance and / or VAF before and after such treatment.

Described herein are methods of inhibiting an allele that contains a mutation in a cell (e.g., treating a subject with an allele that contains a mutation). The method includes delivering to the cell an antisense oligonucleotide that targets a variant allele that is in cis with the mutation (e.g., the mutation is a gain of function mutation or a dominant negative mutation), wherein the cell or subject is heterozygous for the target variant, and the antisense molecule is effective at knocking down expression the target variant allele (e.g., effective at preventing, treating, or ameliorating at least one symptom associated with the mutation). Also described herein are methods of haplotyping a cell or subject, and antisense oligonucleotides that target mutant superoxide dismutase 1 (SOD1) and other genes.

A method of identifying a variant as a somatic variant derived from cell free DNA (cfDNA) identifies the variant at a locus based on differences between the nucleic acid sequence for a cfDNA fragment in a plurality of cfDNA fragments and a nucleic acid sequence for the locus in a reference sequence, where the cfDNA fragments are from a liquid biopsy sample from a subject. A set of cfDNA fragments comprising the variant, in the plurality of cfDNA fragments, determines fragment length metrics. A variant allele fraction (VAF) is determined based on comparison of the number of cfDNA fragments having the variant and the total number of cfDNA fragments mapping to the locus. Clonal hematopoiesis prevalence metrics for the variant are obtained. The fragment length metrics, VAF, and hematopoiesis metrics are inputted into a model thereby obtaining, as model output, whether the variant is a somatic variant derived from cfDNA.

The present disclosure provides methods and compositions for producing, detecting, and selecting soybean plants and seeds comprising at least one high protein CCT (CONSTANS, CO-like and TOC1) domain containing variant allele and introgressing the high protein CCT variant allele into soybean plants. The present disclosure also provides methods and compositions for producing, detecting, and selecting soybean plants producing seeds having a high protein content including breeding methods for introgressing high protein alleles into soybean plants using marker assisted selection using markers linked to or associated with high protein CCT in soybean.

Methods, systems, and software are provided for determining a homologous recombination pathway status of a cancer in a test subject, e.g., to improve cancer treatment predictions and outcomes. In some embodiments, classifiers using one or more of (i) a heterozygosity status for DNA damage repair genes in a cancerous tissue, (ii) a measure of the loss of heterozygosity across the genome of the cancerous tissue, (iii) a measure of variant alleles detected in a second plurality of DNA damage repair genes in the genome of the cancerous tissue, (iv) a measure of variant alleles detected in the second plurality of DNA damage repair genes in the genome of a non-cancerous tissue, and (v) tumor sample purity are provided.

To provide methods and systems for tumor informed circulating tumor fraction estimation.SOLUTION: Methods, systems, and software for estimating circulating tumor fraction are provided. A first plurality of nucleic acid sequences for a plurality of loci in genomic DNA from a solid tumor sample is obtained. A second plurality of nucleic acid sequences for a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the same subject is obtained. One or more somatic mutations is identified in the first plurality of nucleic acid sequences. A variant allele frequency (VAF) for each somatic mutation is determined based on a frequency of the respective somatic mutation in the liquid biopsy sample and a frequency of the corresponding wild type allele in the liquid biopsy sample, thereby determining a set of VAFs. An estimate of the circulating tumor fraction for the subject is determined based on the set of VAFs for the one or more somatic mutations.SELECTED DRAWING: Figure 1A

The application discloses a method for detecting sample cross contamination based on SNP sites and application thereof. The method comprises the following steps: screening SNP sites, simulating data, constructing a model, and evaluating contamination degree according to the model. The screening of SNP sites comprises the following steps: (1) downloading sequencing-related FASTQ files or bam files from a database; (2) performing variation detection on high-throughput sequencing data of each sample in the files to obtain gvcf format files of variation information of the samples; (3) merging all gvcf files of the samples to obtain vcf format variation information of all the samples; and (4) screening SNP sites according to heterozygous state population frequency and variation allele frequency. The application simulates data of stable SNP sites carrying high population frequency, constructs a model, and evaluates contamination degree according to the model. The AF values of these SNP sites in different samples are relatively stable, and are concentratedly distributed near 0, 0.5 and 1; and the dose change of the AF values after the SNP sites contaminate other samples can accurately reflect the degree of sample cross contamination, and the operation is simple, fast and convenient.

Some embodiments of the methods and systems provided herein relate to variant calling from sequence data obtained from a single sample. In some embodiments, a somatic variant can be distinguished from a germline variant based on variant allele frequency in a sample and location in a genome.

The present disclosure provides a probabilistic model for accurate and sensitive somatic single nucleotide variant (SNV) detection in cell-free nucleic acid samples comprising a set of sequence data. A joint genotype may be determined for each locus in the set of sequence data, and germline mutations may be intrinsically removed. A set of filtrations can be applied to eliminate low quality somatic variant calls. Further, a global tumor cell-free deoxyribonucleic acid (cfDNA) fraction and overlapping read mates can be considered, thereby enabling accurate SNV detection and variant allele frequency estimation from samples with low tumor cfDNA fraction. A sensitive early detection of minimal residual disease (MRD) is designed by using the probabilistic model and the machine learning model for distinguishing true variants from sequencing errors.

In one aspect, the disclosure relates to methods for monitoring clonal hematopoiesis of indeterminate potential (CHIP) in a subject, the method including at least performing DNA methylation sequencing on DNA from the subject, performing cell-type deconvolution from the methylation data to estimate a first set of cell-type proportions in the subject, repeating the method to determine a second set of cell-type proportions in the subject, and monitoring a change in variant allele fraction (VAF) using methylation data collected during performance of the method in conjunction with the first set of cell-type proportions and the second set of cell-type proportions. Also disclosed are methods for assessing the performance of a drug for treating a blood cancer.

Provided herein is a method for determining molecular response score for use in predictive model.Molecular response score can be used to monitor and guide the administration of treatment to subject.The molecular response score can be generated by a method comprising: for at least one variant among a plurality of variants classified into somatic cells, determining the weighted average of the first variant allele fraction (MAF) and the weighted average of the second MAF based on the first MAF and the second MAF.

Described herein are methods for improving sensitivity of tumor-informed MRD assays and panels by prioritizing sites to generate patient-specific panel of somatic variants based on expected variant allele frequency such that tumor somatic variants are overrepresented in cfDNA. Machine learning models trained with genomic data are also utilized to select the subset of somatic variants alone or in combination with an expected variant allele frequency.

Provided herein are methods related to measuring clonal fraction of one or more estrogen receptor 1 (ESRI) mutations in a liquid biopsy sample from an individual having cancer, as well as uses, systems, and computer readable storage media related thereto. In some embodiments, the methods comprise measuring a variant allele frequency of one or more ESRI mutations in a liquid biopsy sample obtained from the individual, measuring a tumor fraction of tumor nucleic acid molecules in the liquid biopsy sample, and calculating a ratio of the variant allele frequency of the one or more ESRI mutations to the tumor fraction of tumor nucleic acid molecules in the liquid biopsy sample.

Provided herein is an improved molecular inversion probe protocol, exhibiting reduced noise, high specificity and sensitivity and improved coverage at GC-rich regions.

Provided herein are methods, kits, and related compositions useful for detecting from a biological sample a low variant allele frequency (VAF) by conventional PCR methods by use of two or more specially configured probes. A first universal-type labelled probe would, normally, when hybridized to a sequence, generate an optically-detectable signal by PCR. Provided herein, however, are specially configured oligonucleotides that, when bound, either prevents non-specific binding of labelled probe to the sequence and / or inhibits reference sequence synthesis by PCR. In this manner, even very low populations of sequences in the presence of another population of sequence that could differ by as little as one nucleotide, can be reliably detected by commercially-available PCR systems.

A method of identifying a variant as a somatic variant derived from cell free DNA (cfDNA) identifies the variant at a locus based on differences between the nucleic acid sequence for a cfDNA fragment in a plurality of cfDNA fragments and a nucleic acid sequence for the locus in a reference sequence, where the cfDNA fragments are from a liquid biopsy sample from a subject. A set of cfDNA fragments comprising the variant, in the plurality of cfDNA fragments, determines fragment length metrics. A variant allele fraction (VAF) is determined based on comparison of the number of cfDNA fragments having the variant and the total number of cfDNA fragments mapping to the locus. Clonal hematopoiesis prevalence metrics for the variant are obtained. The fragment length metrics, VAF, and hematopoiesis metrics are inputted into a model thereby obtaining, as model output, whether the variant is a somatic variant derived from cfDNA.

The invention discloses a promoter cis-acting element for regulating and controlling APO1 gene expression and application of the promoter cis-acting element, and belongs to the technical field of plant genetic engineering. From the perspective of APO1 gene expression regulation, a promoter cis-regulation region CRE3 for determining APO1 gene expression is found, and it is proved that a strain with the number of grains per ear and the yield of a single plant remarkably improved can be obtained by conducting editing knockout on a CRE3 sequence through CRISPER / Cas9, two-year plot testing shows that the yield is obviously increased, the stem diameter is increased, and the yield is obviously increased. The method can realize improvement of lodging resistance, can be used for rapid improvement of panicle type and yield of rice varieties, is superior to natural variation alleles in performance, and has extremely high application value.

Methods for detecting a deficient DNA repair mechanism and / or evaluating microsatellite instability in a sample from a subject are described. The disclosed methods comprise analyzing nucleic acid sequence data for a plurality of microsatellite loci to calculate a microsatellite instability (MSI) score for the sample from a ratio of the number of microsatellite loci that exhibit variant alleles to the total number of microsatellite loci that meet, e.g., a minimum sequencing coverage requirement. The MSI score is compared a first threshold and, m some cases, to a second threshold to assign a status of high microsatellite instability′(MSI-H), microsatellite stable (MSS), or equivocal microsatellite instability (MSI-E) for the sample.

Disclosed herein is a method of treatment of an individual suffering from gastroparesis or delayed gastric emptying. In an embodiment, the method comprises selecting an individual for treatment with tradipitant based on a presence of a variant allele in one or more of the SLC4A4, SDK2, LCLAT1, SLC25A16, or CNTN1 genes of the individual; and administering to the selected individual tradipitant at a dose of 150-400 mg / day.

To provide methods useful in determining the cellular origin of a cell-free nucleic acid (cfNA) fragment from a cfNA sample, such as a liquid biopsy sample.SOLUTION: The methods disclosed herein generally improve the specificity and / or sensitivity of an assay for detecting diseased cell nucleic acid (e.g., cancer cell DNA) in a cfNA sample by identifying variant alleles that are produced by non-target cells, such as hematopoietic stem cells in certain embodiments. Still other aspects include, inter alia, related systems and computer-readable media.SELECTED DRAWING: None

Methods are provided for treating a subject having chronic myelomonocytic leukemia (CMML), the method comprising: (a) identifying a RAS pathway mutation in tumor cells of the subject, wherein the RAS pathway mutation is a NRAS, KRAS, PTPN-11 and / or CBL mutation; (b) identifying a dominant CBL mutation of CBL variant allele frequency of from <5% to >10%; and (c) administering to the subject identified in step (a) a therapeutically effective amount of an anti-hGM-CSF antibody.

A method for detecting de novo structural variations includes: a genome analysis apparatus extracting k-mer data of a target individual from genome sequencing data of a target individual. The method may include: extracting k-mer data of a target individual from genome sequencing data, comparing a reference-genome k-mer database—including parents' and pan-genome k-mers—with the target individual's k-mers to select target-individual-specific k-mers, determining target-individual-specific reads, identifying candidate de novo structural-variation regions, predicting discordant read pairs using a machine-learning model, selecting final de novo regions based on an estimated variant allele frequency, and generating a clinical report.

An example method includes receiving sequence read data of nucleic acid molecules in a sample treated with a corrective enzyme after being obtained from a subject and generating a variant allele frequency (VAF) distribution of at least one type of substitution variant of the sequence read data by comparing the sequence read data to a reference genome. Candidate variants are identified in the VAF distribution. At least a portion of the candidate variants are determined to be false positive variants by determining that greater than a threshold number of the candidate variants are present within a threshold range of the VAF distribution. A report is generated based on one or more additional variants, which omit the false positive variants.

Some embodiments of the methods and systems provided herein relate to variant calling from sequence data obtained from a single sample. In some embodiments, a somatic variant can be distinguished from a germline variant based on variant allele frequency in a sample and location in a genome.

The invention belongs to the field of biological medicines, and provides a device for predicting disease recurrence based on an ultrahigh-sensitivity mutation load, an MRD gene detection panel covering 28 hotspot mutation regions of acute myelogenous leukemia is designed by integrating famous tumor public databases such as COSMIC, a quantitative blocker displacement amplification QBDA technology is combined, and the disease recurrence is predicted. According to the method, ultra-low abundance mutation with the variation allele frequency lower than 0.01% can be detected, a set of device for predicting relapse in advance based on ultra-high sensitivity mutation load change in the complete remission period of an acute myelogenous leukemia patient is developed, and the important clinical application value is achieved.

Methods of monitoring the efficacy of treatment in a subject suffering from myelodysplastic syndrome (MDS) are provided. Also provided are methods of identifying a subject having MDS for treatment with a telomerase inhibitor, and methods of treating MDS. The method comprises administering a telomerase inhibitor to the subject, and evaluating a variant allele frequency (VAF) of one or more of the following genes: SF3B1, TET2, DNMT3A, ASXL1, and CUX1 in a biological sample obtained from the subject after administration of the telomerase inhibitor. In some cases, a reduction in VAF by 25% or more identifies a subject having an increased likelihood of benefiting from treatment with a telomerase inhibitor. In some cases, the telomerase inhibitor is imerostat or imerostat sodium.