70 results about "Copy-number variation" patented technology

The invention discloses application of NOR1 copy number variation in prediction of the mature period of pears, and belongs to the technical field of plant molecular markers, by analyzing genomes of pear varieties in different mature periods, it is found that copy number variation exists in DNA fragments where NOR1 is located, the copy number of the NOR1 is positively correlated with the mature period on the basis of analysis of genome assembly and three-generation sequencing data, and the mature period of the pear varieties is predicted. And determining the mature period of the pear according to the copy number of the NOR1. The molecular marker developed by the invention can predict the mature period of the filial generation in the seedling stage, and the breeding efficiency of early-maturing varieties is greatly improved.

The present disclosure provides a system and method for the detection of rare mutations and copy number variations in cell free polynucleotides. Generally, the systems and methods comprise sample preparation, or the extraction and isolation of cell free polynucleotide sequences from a bodily fluid; subsequent sequencing of cell free polynucleotides by techniques known in the art; and application of bioinformatics tools to detect rare mutations and copy number variations as compared to a reference. The systems and methods also may contain a database or collection of different rare mutations or copy number variation profiles of different diseases, to be used as additional references in aiding detection of rare mutations, copy number variation profiling or general genetic profiling of a disease.

The invention discloses a method for accurately identifying benign and malignant cells based on multi-dimensional characteristics of a single cell transcriptome, and belongs to the technical fields of bioinformatics, tumor molecular biology and cell identification. On the basis of single cell transcriptome sequencing data of tumor tissues and para-carcinoma tissues, three types of information including copy number variation, allele specific copy number variation and tumor-related transcriptional characteristics are synthesized, and final benign and malignant identification is performed on each EpCAM positive epithelial cell through a multi-evidence voting strategy. The method disclosed by the invention has relatively high stability and accuracy in a multi-patient, multi-sample and early tumor scene, particularly improves the recognition capability of early lesion and malignant cells in benign and malignant boundary transition state cells, and provides a reliable technical means for precise diagnosis and individualized treatment of tumors.

The application discloses a kind of marker for predicting oocyte copy number variation and application thereof, the marker includes the combination of CLEC11A, P4HB, EFEMP2, IL32, FTL, FLNA, COL6A3, ACPP and APOO protein.By the marker of the application, the expression level of granulosa cell secretory protein can be determined by granulosa cell transcriptome sequencing, and the genomic CNV condition of corresponding oocyte can be inferred.The detection object of the technical solution is discarded granulosa cell in assisted reproductive technology, so it will not have any impact on oocyte, and it is non-invasive;The present study is a transcriptome and methylation group detection from single cell level, with high-throughput characteristics, and all granulosa cells and oocytes are one-to-one matched, which can reflect the difference between single cell level COCs.

The invention relates to a method of determining somatic allele-specific copy number alterations (CNAs) in the genomes of cells in a test-sample from a subject, the method comprising: i) providing an indexed-DNA library of DNA fragments resulting from whole-genome amplification of genomic DNA from cells of the test-sample, ii) providing whole genome sequencing data of reference non-cancer cells from a reference-sample from the subject; and iii) determining somatic allele-specific copy number alterations in the genome(s) of the cells of the test-sample; and associated methods and uses in cancer therapy.

The application discloses a single cell whole genome amplification sequencing method. The application comprises the following steps: 1) separating a single cell, adding a single cell lysis solution to sufficiently lyse the single cell and digest proteins combined on the genomic DNA; 2) using a Tn5 transposome with a specific adapter sequence to fragment the DNA, while adding adapters to both ends of the fragments; 3) after end repair, using a ribonuclease to cut modified ribonucleotide residues on the adapter sequence; 4) using the adapter sequence as a primer to linearly amplify the fragmented DNA by using a single primer PCR method; and 5) adding sequencing adapters to both ends of the DNA fragments by using a chain extension and PCR method to obtain a final sequencing library. The method disclosed by the application can amplify single cell whole genome DNA with high coverage, uniformity and fidelity, and simultaneously and accurately detect chromosomal copy number variation CNV and single nucleotide mutation SNV on a single cell genome.

The invention provides an exon copy number variation detection method, device and equipment, and relates to the technical field of high-throughput sequencing, the method comprises the following steps: inputting feature information of a to-be-detected sample in each target interval into a target hybrid expert model, and outputting a reliability score of copy number variation of the to-be-detected sample in each target interval; obtaining the reliability grade of the copy number variation of the exon interval according to the reliability grade of the copy number variation of each target interval; updating the reliability grade of the copy number variation of the exon interval of the to-be-detected sample to obtain the reliability grade of the copy number variation of the updated exon interval; and filtering the copy number variation of the exon interval, and determining an exon copy number variation detection result of the sample to be detected. According to the method provided by the embodiment of the invention, exon copy number variation can be accurately detected.

The application provides an exon copy number variation detection method, device and equipment, and relates to the technical field of high-throughput sequencing, which comprises the following steps: inputting characteristic information of a sample to be detected in each target interval into a target hybrid expert model, and outputting reliability scores of copy number variations of the sample to be detected in each target interval; obtaining reliability classification of copy number variations of an exon interval according to the reliability scores of copy number variations of each target interval; updating the reliability classification of copy number variations of the exon interval of the sample to be detected, and obtaining updated reliability classification of copy number variations of the exon interval; and filtering the copy number variations of the exon interval, and determining an exon copy number variation detection result of the sample to be detected. The method of the application embodiment realizes accurate detection of exon copy number variations.

The present invention provides methods, compositions and kits for using a transposase and a transposon end for generating extensive fragmentation and 5′-tagging of double-stranded target DNA in vitro, then using a DNA polymerase for generating 5′- and 3′-tagged single-stranded DNA fragments without performing a PCR amplification reaction, wherein the first tag on 5′-ends exhibits the sequence of the transferred transposon end and optionally, an additional arbitrary sequence, and the second tag on 3′-ends exhibits a different sequence from the sequence exhibited by the first tag. The method is useful for generating 5′- and 3′-tagged DNA fragments for use in a variety of processes, including processes for metagenomic analysis of DNA in environmental samples, copy number variation (CNV) analysis of DNA, and comparative genomic sequencing (CGS), including massively parallel DNA sequencing (so-called “next generation sequencing”).

This invention discloses a method and system for assessing tumor content in liquid biopsies. The method performs quality control on high-throughput sequencing data from body fluid samples, filtering germline variations, clonal hematopoietic-related variations, and sequencing errors to obtain copy number variation (CNV) information and somatic mutation characteristic information. A weighted mean squared error loss function is constructed based on the CNV information, and the tumor content is solved using a constrained gradient descent method. When the CNV signal does not meet preset judgment conditions, the system switches to the mutation characteristic module, constructing a negative log-likelihood function based on a binomial distribution based on the principal clonal cluster, and solving for the tumor content through iterative optimization. In extreme cases, a backoff mechanism is triggered. This invention combines the stability of CNV at high tumor content with the sensitivity of mutational VAF at low content, achieving adaptive assessment from low to high tumor content.

Methods of identifying genetic mutations and / or genetic alterations are provided.SOLUTION: Methods for classifying the presence or absence of genetic mosaicism for a copy number variation in one or more fetuses (e.g., predicting whether a fetus or more than one fetus is affected by a copy number variation) are provided. The sample nucleic acid is subjected to a sequencing process and the resulting sequence reads are analyzed to identify genetic copy number variation regions. Genetic mosaicism for a copy number variation region is classified for a fetus or more than one fetus based on (i) a mosaicism ratio of a fraction of nucleic acid having the copy number variation region to a fraction of fetal nucleic acid and (ii) a chromosome having the genetic copy number variation region (e.g., an identified type of aneuploidy) or (ii) a number of fetuses carried by a pregnant female.SELECTED DRAWING: None

The application discloses a tumor cell line drug response prediction method integrating multiple omics and essential gene information, relates to the field of tumor drug response prediction, and is a DROEG prediction method (Drug Response based on Omics and Essential Genes). Four kinds of omics data, including gene expression data, copy number variation data, methylation data and somatic mutation data, and CRISPR gene effect data (CERES Score) are introduced to construct a drug response model, and the effect of the model is comprehensively evaluated by a qualitative evaluation method and a quantitative evaluation method. The application introduces CRISPR essential gene information, establishes a drug response prediction model, is more accurate than existing methods, has the functions of quantitative and qualitative prediction and evaluation, is more suitable, and is more flexible to operate.

The application discloses a kind of gene markers in esophagus, stomach, intestine multiple cancer early screening application, early screening model construction method and detection device, belong to the early non-invasive detection technical field of digestive tract tumor.It establishes a new type of multiple cancer screening system by analyzing the whole genome characteristics of circulating free DNA in peripheral blood.Based on low-depth whole genome sequencing data, three dimensions of molecular markers are detected: genome copy number variation pattern, DNA fragment distribution characteristics of specific length and epigenetic signals of transcription initiation region.Advanced converter neural network architecture is used, and the model can efficiently capture the complex feature correlation in the whole genome range through its unique self-attention mechanism.The model design specially considers the particularity of genomic data, and introduces an adaptive position coding system to accurately reflect the spatial distribution relationship of DNA fragments on the chromosome.The system can still maintain excellent detection performance at very low sequencing depth.

The application provides a gene fragment recurrent copy number variation detection method based on deep learning, which comprises the following steps: (1) grouping, classifying and performing numerical conversion preprocessing on obtained gene data; (2) performing data modeling on the preprocessed data, and converting the original segmented data into a matrix form; (3) performing multi-scale sliding window sampling on the obtained matrix to obtain a data set; (4) performing data set labeling according to the visual features of the data; (5) training a constructed neural network by using the labeled data set; and (6) collecting gene data, inputting the gene data into the trained neural network after processing through steps (1)-(3), and outputting a recurrent copy number variation region.

The present application provides a marker combination for early detection of digestive system cancer, tissue localization, diagnosis, prognosis detection and identification of benign and malignant, the marker combination is selected from 1656 chromosome regions in table 1. A multi-cancer early screening and localization technology GutSeer for five high mortality digestive system cancers is also provided, which proves that using a relatively small second-generation sequencing panel can realize accurate cancer detection and organ tissue localization by using multiple dimensional characteristics including methylation, copy number variation and terminal motif.

This specification discloses methods for identifying stable control loci for use in fluorescence in situ hybridization (FISH) assays, and methods for determining whether copy number changes (e.g., amplification) of a target genomic locus (e.g., a gene, e.g., cyclin E1 (CCNE1)) have occurred in a biological sample (e.g., a non-neoplastic sample, a pre-neoplastic lesion, and / or a tumor). In particular, this disclosure provides an expanded repertoire of genomic loci that can serve as stable controls (e.g., stable control loci) for FISH assays aimed at determining copy number changes of a target genomic locus.

The invention belongs to the field of genetics detection, and particularly relates to a genetics-integrated single-molecule sequencing detection kit and system before embryo implantation. Specifically, the kit and the system provided by the invention can realize synchronous detection of human pre-implantation embryo aneuploid, copy number variation, chromosome structure abnormality and monogenic diseases. According to the method, the parent sample and the embryo sample are subjected to single molecule length reading sequencing, family members except a certificate and parents are not needed, direct detection of aneuploidy, copy number variation, chromosome structure abnormality and the like and indirect detection based on haplotype inference are achieved, the detection result is accurate, sensitive and visual, and information is comprehensive. According to the kit and the system disclosed by the invention, only the same experimental system and the same single-molecule long-fragment sequencing platform are needed, so that PGT-A, PGT-M, PGT-SR and haplotype genetic condition detection can be completely supported, the process is simple and convenient, the application range is wide, and therefore, the kit and the system have a good practical application value.

The application discloses a quality control method for detecting copy number variation of second-generation whole exome sequencing and application. The quality control method comprises the following steps: obtaining whole exome sequencing data of a sample to be detected, and calculating average sequencing depth of a probe region; matching the average sequencing depth of the sample to be detected with average sequencing depths of reference samples in different batches; if a matching condition is met, selecting corresponding depth reference sample sequencing data, and performing subsequent quality control on the sample to be detected; if the matching condition is not met, the sample to be detected cannot be used for copy number variation analysis; calculating STD and NEDDI of the sample to be detected, and comparing the STD and NEDDI with a quality control model; if the STD and NEDDI are located below a curve of the quality control model, the sample to be detected passes the quality control; otherwise, the sample to be detected does not pass the quality control. The application innovatively performs quality control grading in a data preprocessing stage, judges whether a sample is suitable for copy number abnormal genetic analysis, significantly improves variation detection accuracy and reliability, and provides efficient technical support for clinical practical application.

The application provides a STRC gene copy number variation detection method based on whole genome sequencing. The STRC gene and the STRCP1 gene are subjected to sequence alignment to find each difference site of the STRC gene and the STRCP1 gene. For each difference site, the sequence of the corresponding STRC position and STRCP1 position in the genome is read from a variation detection file. The total copy number of the true gene and the false gene is calculated by taking the reference site in the genome as a reference. The STRC gene copy proportion on each difference site is calculated. The STRC gene copy number on each difference site is calculated according to the total copy number and the STRC gene copy proportion. The STRC gene copy number on each exon is determined according to the STRC gene copy number on each difference site. The method can realize the detection of the STRC copy number, simplifies the detection process, improves the detection throughput and reduces the cost.

Embodiments of the present application disclose a cancer auxiliary diagnosis device, a training method, an electronic device and a storage medium. In a specific embodiment, the structure comprises: a data input layer configured to receive DNA methylation data, transcriptome data and copy number variation data; a first attention mechanism module configured to fuse features of the DNA methylation data and corresponding transcriptome data to obtain first fused features; a second attention mechanism module configured to fuse features of the DNA methylation data and corresponding copy number variation data to obtain second fused features; a feature splicing module configured to splice the first fused features and the second fused features to obtain spliced features; a fully connected layer configured to reduce the spliced features to an m-dimensional vector; and a classifier configured to map the m-dimensional vector to obtain probability values of m classifications of cancer. The embodiment can reduce the redundancy between features and effectively improve the accuracy of cancer diagnosis.

The invention discloses a differential diagnosis and prognosis evaluation method for a pleural effusion microbiome based on metagenome sequencing and application, belongs to the technical field of bioinformatics, and discloses a method for analyzing the microbiome of a pleural effusion sample, and the method comprises the following steps: carrying out metagenome next-generation sequencing on an in-vitro pleural effusion sample to obtain a sequencing reading; performing bioinformatics analysis on the sequencing reading, and determining microorganism composition information of the pleural effusion sample based on a verification result; by establishing a unified mNGS experimental process and a parallel bioinformatics analysis path, two kinds of technical information of different dimensions, namely microbiome structural characteristics and host genome copy number variation (CNV), are synchronously output from single sequencing data, and the defect that microbiological analysis and genome analysis need to be carried out in batches in the prior art is overcome.

The application belongs to the technical field of gene detection and molecular diagnosis, and particularly relates to a kit for detecting a pathogenic gene of phenylketonuria and application thereof. The kit comprises a primer pair for amplifying specific exons and splicing regions of a phenylalanine hydroxylase gene, and specific probes for detecting hot spot mutations and deletion / repetition variations of the gene. The application can detect genetic variations related to phenylketonuria in one time, quickly and accurately by combining optimized multiplex polymerase chain reaction with high-throughput sequencing or gene chip technology, and covers various known hot spot mutations and copy number variations including c.1222C>T, c.1068-11G>A, c.728G>A and c.1162G>A. The kit has high detection sensitivity and strong specificity, and is suitable for positive recall diagnosis of neonatal phenylketonuria screening, genetic diagnosis of suspected patients, carrier screening and prenatal diagnosis, and provides an efficient tool for precise prevention and control of phenylketonuria.

The present invention relates to an improved method for diagnosing homologous recombination deficiencies (HRDs) in tumors. The method according to the present invention comprises the steps of: evaluating the number of large genomic alterations (LGAs) in a tumor sample by obtaining a copy number alteration (CNA) profile by shallow coverage whole-genome sequencing (sWGS); and determining an LGA score corresponding to the number of LGAs adjusted for the complexity of the tumor genome and the presence of one or two markers selected from a group of markers consisting of (1) phenotypes associated with mutations in cyclin-dependent kinase 12 (CDK12) with multiple intermediate gains in the CNA profile; (2) amplification of cyclin E1 (CCNE1); (3) amplification of human epidermal growth factor receptor-2 (HER2); and (4) phenotypes of amplification at multiple sites.

The invention discloses a cancer-related gene comprehensive scoring method and system based on multi-modal deep learning. Comprising the following steps: 1, obtaining scores corresponding to gene expression, copy number variation, methylation and somatic mutation processes, forming a feature vector by using the gene expression score, the copy number variation score, the methylation score and the somatic mutation score, and preprocessing the feature vector to obtain a standardized feature vector; 2, carrying out weight fusion on the standardized feature vectors, and calculating a comprehensive score; 3, constructing a multi-modal integrated model, and training the model by taking the comprehensive score as a model training target; and 4, carrying out score prediction on the genes by utilizing the trained multi-modal integrated model, outputting predicted scores, and carrying out gene list sorting according to the predicted scores. The method is suitable for mining key genes related to cancer occurrence and development from high-throughput sequencing data, and can be applied to tumor molecular mechanism research, prognostic marker screening and precise medical scheme formulation.

Disclosed herein are systems and methods for performing secondary analysis of nucleotide sequencing data in a time-efficient manner. Some embodiments include iteratively performing secondary analysis as sequence reads are generated by a sequencing system. Secondary analysis can include alignment of sequence reads to a reference sequence (e.g., a human reference genome sequence) and use of the alignment to detect differences between a sample and the reference. Secondary analysis can be capable of detecting genetic differences, variant calling and genotyping, identifying single nucleotide polymorphisms (SNPs), small insertions and deletions (indels), and structural changes in DNA, such as copy number variations (CNVs) and chromosomal rearrangements.

The invention discloses a method for generating high fidelity sample sequencing data. The method aims at accurately simulating copy number variation in a genome. According to the method, a traditional de novo generation model is innovatively abandoned, and an in-situ editing strategy based on real data is adopted. According to the method, on the basis of real sequencing data, reading segments of a specific region of a genome are accurately removed or quantitatively supplemented, and all endogenous system deviations and noise in base data are completely reserved while known copy number variation is introduced. Compared with the prior art, the method has the advantages that the core pain point of analog data distortion is solved, the reference data set highly consistent with real tumor sample features is generated, reliable data support is provided for performance evaluation and calibration of a downstream algorithm, the research and development process is remarkably accelerated, and the research and development cost is remarkably reduced.

The invention discloses an ultrahigh-sensitivity chromosome copy number variation detection system and method, and belongs to the technical field of biological detection and gene sequencing. The technical problems to be solved are that an existing detection system lacks multi-feature integration capability, signal enrichment is weak, a threshold value is fixed, and sensitivity and anti-interference performance are insufficient. According to the technical scheme, the system is characterized by comprising a sample processing and sequencing module, a data preprocessing and quality control module, a multi-dimensional feature extraction module, a signal enrichment and model prediction module and a dynamic threshold value screening and result judgment module. And enriching signals through an integrated model and multiple attention mechanisms, fitting a dynamic threshold value based on a healthy person reference sample, and outputting a scenarized detection result in combination with multi-standard verification.

The present disclosure provides a system and method for the detection of rare mutations and copy number variations in cell free polynucleotides. Generally, the systems and methods comprise sample preparation, or the extraction and isolation of cell free polynucleotide sequences from a bodily fluid; subsequent sequencing of cell free polynucleotides by techniques known in the art; and application of bioinformatics tools to detect rare mutations and copy number variations as compared to a reference. The systems and methods also may contain a database or collection of different rare mutations or copy number variation profiles of different diseases, to be used as additional references in aiding detection of rare mutations, copy number variation profiling or general genetic profiling of a disease.

The invention discloses a digital PCR detection system, kit and method for detecting single nucleotide polymorphism and copy number variation of a CYP2D6 gene and application, and belongs to the technical field of molecular biology. The method comprises the following steps: designing three pairs of CYP2D6 and reference gene RPP30 specific primers, matching with four locked nucleic acid modified TaqMan fluorescent probes, constructing a single-tube multiple digital PCR detection system, and synchronously and accurately detecting three single nucleotide polymorphisms of CYP2D6 * 10, CYP2D6 * 36 and CYP2D6 * 41 and CYP2D6 * 5 copy number variation; wherein the RPP30 reference gene can synchronously realize sample amplification quality control and target gene absolute quantitative calibration. The detection system depends on the advantages of high specificity of the LNA probe and high sensitivity of digital PCR, the detection sensitivity reaches 0.02 ng / mu L, the detection period is short, and the result is stable and reliable.

The invention is applicable to the technical field of bioinformatics and molecular diagnosis, and provides a TP53 gene heterozygosity deletion and copy number variation detection method based on targeted sequencing, and synchronous and accurate detection of LOH / CNV and mutation of a TP53 gene is realized through core technology innovations such as customized probe design, dynamic reference set correction, HMM model improvement and KDE double-peak judgment; compared with a traditional detection technology, the problems of CN-LOH leak detection and insufficient integrated analysis of mutation and structural variation are effectively solved, and the coincidence rate with whole exon sequencing reaches 100%; the method has the outstanding advantages of high sensitivity, high specificity, rapidness, high efficiency and controllable cost, can accurately judge the multiple strike states of TP53, provides a reliable molecular diagnosis basis for risk stratification, prognosis evaluation and individualized treatment decision of patients with myeloid tumors such as AML / MDS, and is more suitable for clinical conventional popularization and application.