134 results about "Copy-number variation" patented technology

The invention discloses application of a gene marker in early screening of esophagus, stomach and intestine multiple cancer species, an early screening model construction method and a detection device, and belongs to the technical field of early noninvasive detection of digestive tract tumors. By analyzing the whole genome characteristics of circulating free DNA in peripheral blood, a novel multi-cancer-species screening system is established. On the basis of low-depth whole genome sequencing data, molecular markers in three dimensions, namely a genome copy number variation mode, a DNA fragment distribution characteristic with a specific length and an epigenetics signal of a transcription initiation region, are emphatically detected. An advanced converter neural network architecture is adopted, and the model can efficiently capture complex feature association in a whole genome range through a specific self-attention mechanism. The model design particularly considers the particularity of genome data, introduces an adaptive position coding system, and accurately reflects the spatial distribution relationship of DNA fragments on chromosomes. Therefore, the system can still maintain excellent detection performance under extremely low sequencing depth.

The invention provides a primer probe combination and a kit for detecting the copy number of a 22q11 region based on digital PCR and a use method of the primer probe combination. Specific probes of a target gene TBX1, a target gene CRKL, a target gene SMARCB1 and a reference gene GAPDH are integrated in different fluorescence channels, and the copy number of the target gene is detected according to the ratio of the copy number of the reference gene to the copy number of the three target genes. According to the invention, amplification products of different sites in different fluorescence channels are integrated in the same system in digital PCR reaction, so that the detection flux is greatly improved, and low-cost and high-flexibility accurate quantification of 22q11. 2 copy number variation is realized through a single-channel multi-target fluorescence layering strategy; and the dependence on expensive equipment, complex operation and professional analysis in the prior art is overcome.

The invention relates to the technical field of assisted reproduction polygene detection, and discloses an oocyte occurrence and maturation disorder detection panel, a detection kit and application thereof, and the detection panel comprises mutation genes related to the oocyte occurrence and maturation disorder for detection, copy number variation genes and rearrangement event and deletion genes. According to the application, by detecting high-risk genes and mutation sites, the risk of occurrence and maturation disorder of the oocytes is predicted in combination with clinic, the development potential of the oocytes is evaluated, the in-vitro maturation strategy is optimized, and the clinical outcome of assisted reproduction is improved. The detection panel can be used for efficiently detecting gene mutation which has clinical diagnosis and treatment significance on oocyte occurrence and maturation disorders; the method has important guiding significance on genetic counseling, risk prediction, clinical diagnosis, precise treatment and potential personalized intervention measures of patients suffering from recurrent oocyte occurrence disorder, oocyte maturation disorder and low oocyte maturation rate and patients to be subjected to assisted reproduction technology treatment.

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.

According to the application of the HTATSF1 gene in regulation and control of cattle muscle growth and development and breeding, the influence of the HTATSF1 gene on muscle growth and development and the correlation between HTATSF1-CNV and cattle growth traits are verified, a reliable molecular marker is provided for cattle seed selection and breeding, and help is provided for cattle variety improvement. A foundation is laid for association between copy number variation and growth traits of the cattle HTATSF1 gene, cattle molecular marker-assisted selection breeding work can be accelerated, the method is simple, rapid and convenient to popularize and apply, and a complete solution from fundamental research to industrial application is provided for improvement of cattle germplasm resources.

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 invention discloses a probe group for detecting copy number variation of pathogenic genes of limb development defect diseases as well as a design method, a kit and application of the probe group, and belongs to the technical field of biomedicine. The probe group comprises probes of which the nucleotide sequences are as shown in SEQ ID NO. 1 to SEQ ID NO. 516. The invention also discloses a design method of the probe group, a kit comprising the probe group, and a method for detecting copy number variation of the pathogenic gene of the limb development defect disease by using the probe group or the kit. The probe group and the kit provided by the invention can realize high-throughput, high-resolution, high-accuracy and low-cost copy number variation detection.

Provided herein are, inter alia, are methods and systems for amplifying a chromosomal fragment DNA sequence. The methods and systems provided herein are, inter alia, useful for detecting copy number variation, structural variation, and / or extrachromosomal DNA within the chromosomal DNA of a plurality of cells. In addition, the methods provided herein are, inter alia, useful for jointly analyzing chromatin architecture and gene expression at a single cell level. The methods provided herein can be, inter alia, used to analyze chromosomal heterogeneity, clonal shifts, and / or evolutionary shifts between different cells.

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.

The invention discloses a resequencing-based space mutagenesis peanut population genotype variation map and a construction method thereof, and belongs to the technical field of plant biotechnology and plant molecular breeding, and the technical key points are as follows: a space mutagenesis peanut mutant plant is utilized, based on a whole genome resequencing technology, genetic variation sites in a genome are systematically detected, and the genotype variation map of the space mutagenesis peanut population is obtained. A variation map of a space mutagenesis peanut population genome is constructed, the map comprises no less than 500,000 mononucleotide variations (SNP), 100,000-200,000 insertion and deletion (InDel), about 3000 copy number variations (CNV) and about more than 3000 structural variations (SV), and 66 genes related to peanut grease anabolism are screened out. The construction method comprises the following steps: obtaining a mutant plant, extracting DNA, sequencing, detecting and identifying SNP, InDel, CNV and SV variation sites, and the like.

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 belongs to the technical field of biological information detection, and discloses a gene copy number variation detection method, according to the confidence interval determination of copy abnormal sites, clustering, determining the copy abnormal sites belonging to the high copy variation sub-class and the RD value being greater than the corresponding confidence interval and the copy abnormal sites belonging to the low copy variation sub-class and the RD value being less than the corresponding confidence interval as the copy variation sites, merging the copy variation sites with adjacent positions and the same variation type to obtain more accurate CNV fragments, separating the interval size of the RD site and the interval size of the CNV fragment, so that the resolution of the RD site can be improved while the stability of the CNV fragment is ensured, and the unsupervised machine learning method is used for the clustering classification of the copy abnormal sites and the comparison with the confidence interval, so that the copy variation sites are double-recognized, the recognition accuracy of the copy variation sites is further improved, and the accuracy, sensitivity and stability of the CNV detection are improved.

The invention discloses application of an HAVCR2 gene in cattle molecular marker-assisted selective breeding, and belongs to the technical field of molecular genetics. The method comprises the following steps: by taking cattle genome DNA as a template, amplifying a cattle HAVCR2 gene copy number variation region by utilizing a specific PCR primer, amplifying a cattle BTF3 gene partial segment as an internal reference, and finally calculating and judging the individual copy number variation type by utilizing a 2 * 2-delta delta Ct method. The method provided by the invention lays a foundation for establishing association between cattle HAVCR2 gene copy number variation and growth and development, can be used for cattle molecular marker-assisted selective breeding work, and is convenient to popularize and apply.

The application discloses a method for identifying spotted neapolitan cow breeds by using bovine chromosome 6 copy number variation. Genome candidate region copy number variation analysis is carried out on selected neapolitan cow breeds with different spotted hair color traits; according to the found copy number variation segment of the genomic region 6:70230801-70291600 located on bovine chromosome 6, the copy number variation types of individuals are identified, low-cost and accurate identification of spotted neapolitan cow and solid color neapolitan cow breeds at the DNA level is realized, and the genetic breeding efficiency is improved.

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.