46 results about "Genome human" patented technology

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing enzymes or enzyme domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing enzymes or domains, are provided.

A system is disclosed for discreetly assessing the compatibility of two or more human genomes across diverse elements, activities, and engagement platforms relevant to potential mating scenarios. The genomic data is subjected to encryption, with the option of employing homomorphic encryption to safeguard user privacy and security. Processing of the data is facilitated through a personal health database processing system, which may be cloud-based or edge-based. The application of homomorphic encryption ensures that the genomic information of individual users remains encrypted during processing, with the outcome limited to the display of progeny compatibility to the respective end users.

The invention discloses a haploid modeling method based on generic genome genetic information, relates to the technical field of genetic engineering, and aims to ensure existence of'essential genes' in human genomes as much as possible through a core sequence mechanism and a sliding window mechanism in order to solve the problem of low haploid modeling efficiency in the prior art. And the generic genome is divided into a plurality of core windows, so that a single window becomes parallel after being a relatively independent individual, modeling supporting high parallelization is realized, and the modeling efficiency is improved on the basis of ensuring real modeling.

Among other things, provided herein are systems that replace the natural random integration activity of a retrovirus with site-specific integration machinery. This approach allows for a more precise targeting of a gene of interest into a human genome, e.g., for therapeutic purposes. The system may include integration-deficient retrovirus (e.g., lentivirus) (IDLV), in which the natural integration activity has been reduced (e.g., by mutation to the viral integrase polypeptide). Instead, the system may comprise a site-specific recombinase (e.g., a serine recombinase, e.g., a serine integrase) capable of directing insertion of a template DNA, or portion thereof, into a desired site in the human genome.

The present invention discloses an in vitro method for obtaining DNA methylation biomarkers as exquisite DNA methylation positions in the human genome (i.e., CGIDs) that predict cervical cancer especially at as yet inaccessible early stages by examining progression of “categorical” DNA methylation alterations in three stages of premalignant lesions (cervical intraepithelial neoplasia (CIN)), progressing from CIN1 to CIN3. The present invention discloses combinations of CGIDs for detecting with high specificity and sensitivity cervical cancer by measuring their DNA methylation status and deriving a “methylation score”, which is useful as a biomarker for cervical cancer. Also disclosed are kits for predicting cervical cancer using such CGIDs using multiplexed next generation sequencing methylation assays, pyrosequencing assays and methylation specific PCR. The DNA methylation markers (CGIDs) described in the present invention are useful for cervical screening and early detection of cervical cancer by any person skilled in the art to detect cervical cancer.

The invention discloses an SNP (Single Nucleotide Polymorphism) site related to the risk of liver injury caused by methotrexate and application of the SNP site. The SNP is located at 31, 356 and 966bp positions of a No.6 chromosome of a human GRCh38 genome, and the basic group of the SNP is C or G. According to the scheme, the SNP site related to the methotrexate liver injury is provided, the risk of the liver injury caused by methotrexate can be effectively predicted, and the SNP site serves as a marker for predicting the liver injury caused by methotrexate.

A genetic prime editing screening platform to identify functional variants related to human health and disease, is configured substantially to annotate genome with nucleotide resolution with actionable disease prediction and treatment for personalized medicine.

A gene-leader editing screening platform for identifying functional variations associated with human health and disease, substantially configured to annotate genomes with nucleotide resolutions, accompanied by operable disease prediction and treatment for personalized medical treatment.

Disclosed are methods of preparing a composition of non-naturally occurring DNA, comprising: (a) extracting DNA from a sample of a subject; (b) contacting the extracted DNA or its derivative with a panel of oligonucleotide probes designed to hybridize to a plurality of preselected genomic regions, thereby generating selected DNA, wherein at least 50% of the preselected genomic regions are CpG regions that each comprises at least 3 CpG sites and a CpG density of at least 0.02 CpG / bp, wherein the preselected genomic regions cover 10-500 Mb of sequence space in human genome, wherein the extracted DNA or its derivative or the selected DNA or its derivative is further treated with an agent or a combination of agents that discriminates between methylated and unmethylated cytosines; and (c) performing high-throughput sequencing on the selected DNA or its derivative and generating sequencing reads.

A method for detecting fetal CNVs through non-invasive prenatal testing, comprising steps: (a) collecting blood samples from pregnant women; (b) extracting cfDNA fragments from the blood samples, performing whole genome sequencing on extracted cfDNA fragments to obtain cfDNA sequencing data, and preprocessing cfDNA sequencing data by removing adapters, aligning and mapping reads to a referenced human genome; (c) performing quality control on obtained cfDNA sequencing data for being accepted for the prediction; (d) dividing referenced genome into a plurality of non-overlapping bins and filtering the bins based on a predetermined GC-content threshold for bins; (e) defining a CNV detection window, a bin size, a set of features for machine learning / deep learning models and fine-tune model for detecting fetal CNV for selecting a final model; and (f) applying the final model to predict fetal CNVs, including microdeletion syndromes, or microduplications, or aneuploidies, or the number of sex chromosomes.

A genomic data analyzer may be configured to detect and characterize, with a variant calling module, genomic variants from next generation sequencing reads out of a pool of enriched genomic patient samples without suffering from next generation sequencing workflow biases such as those introduced by sequencing errors in particular in repeat patterns regions of the human genome such as homopolymers or heteropolymers. The variant calling module may estimate the probability distribution of the length of the repeat pattern for each patient sample and cross-analyze it against other samples in a single experimental pool to identify best-fit variant models for each pair of samples. The variant calling module may further group samples according to their matching best-fit variant models and identify which group of patient samples carries the wild type reference without the need for control data in the pool. The variant calling module may subsequently characterize the homozygous or heterozygous repeat patterns variants for each patient sample with improved specificity and accuracy even in the presence of next generation sequencing biases.

The invention relates to the technical field of biological medicine, in particular to a molecular marker of alveolar rhabdomyosarcoma and application of the molecular marker, the molecular marker is a circPAX3R-loop site, and a DNA-RNA hybridization region of the molecular marker is located on chr2: 2230 94913-2230 95853 of a human genome. According to the application disclosed by the invention, a large number of R-loop structures exist in an alveolar rhabdomyosarcoma cell through DRIP-seq, a plurality of circRNAs exist in a cell nucleus of the alveolar rhabdomyosarcoma through circRNA sequencing, the existence of circPAX3R-loop is proved through qPCR after a DRIP product is subjected to RNase R and RNase H treatment, and the result shows that circPAX3R-loop exists in the cell nucleus of the alveolar rhabdomyosarcoma in the cell nucleus of the alveolar rhabdomyosarcoma in the cell nucleus of the alveolar rhabdomyosarcoma. The important clinical application value is realized on developing a reagent or a kit for diagnosing the alveolar rhabdomyosarcoma, a medicine for preventing and / or treating the alveolar rhabdomyosarcoma or a gene treatment strategy aiming at the target spot.

The invention provides a screening method and application of a human low-recombination-rate region micro-haplotype genetic marker. The screening method comprises the following steps: dividing a human genome into a low-recombination-rate region and a high-recombination-rate region; identifying a haplotype which is less than 200bp in length and contains 2-5 SNPs from a low recombination rate region, and taking the haplotype as a micro haplotype; calculating forensic medicine parameters of each micro haplotype; the forensic parameters comprise individual identification capability, non-father exclusion rate and effective allele number; screening out micro haplotypes with forensic parameters within a preset range; and evaluating the paternity identification efficiency of the screened micro-haplotypes by using the contribution degree of the product, and sequencing. According to the invention, the genetic marker is screened from a low recombination region, so that the interference of exchange recombination between homologous chromosomes in a cell meiosis (passage) process on a paternity identification result can be effectively avoided; meanwhile, the paternity identification efficiency of the genetic marker is evaluated through the product contribution degree, the individual identification ability and the paternity exclusion rate can be comprehensively considered, and a favorable basis is provided for selection of the genetic marker.

This invention relates to the field of biomedical technology and discloses a broad-spectrum antimicrobial peptide and its applications. The invention obtains a broad-spectrum antimicrobial peptide H by mining non-classical open reading frames (ncORFs) in the human genome. Experimental verification shows that the broad-spectrum antimicrobial peptide H has significant inhibitory effects on both Gram-positive bacteria (Staphylococcus aureus ATCC 29213) and Gram-negative bacteria (Escherichia coli K88). Furthermore, the broad-spectrum antimicrobial peptide H can form an α-helix. The α-helix structure projection diagram shows that one side is rich in positively charged hydrophilic amino acid residues, and the other side is rich in hydrophobic amino acid residues, exhibiting good amphiphilicity. In addition, the broad-spectrum antimicrobial peptide H provided by this invention has low hemolytic activity and no cytotoxicity, ensuring in vivo safety while achieving highly efficient bactericidal activity. It also features a short synthetic sequence, small molecular weight, and is easy to chemically synthesize.

The present application relates to the technical field of biological medicine, and in particular to a molecular marker of alveolar rhabdomyosarcoma and application thereof, wherein the molecular marker is circFOXO1R-loop site, and a DNA-RNA hybridization region thereof is located at chr13:41133915-41134263 of a human genome. In the present application, the circFOXO1R-loop site is verified by CUT&Tag-qPCR and DRIP-qPCR, and it is found that the circFOXO1R-loop can promote the combination of FOXO1 gene and RNAPol II and DNA damage, and it has important clinical application value for developing a reagent or kit for diagnosing alveolar rhabdomyosarcoma, a drug or a gene therapy strategy for preventing and / or treating alveolar rhabdomyosarcoma aiming at the target.

The present invention discloses the application of a dual liver cancer molecular marker in the preparation of liver cancer detection reagent products, belonging to the technical field of detection kits. The dual liver cancer molecular marker is a composition of DNA methylation dual liver cancer molecular markers screened by the inventor from human genome regions covering more than 10 times the 450K chip range through two rounds of targeted methylation sequencing and suitable for early liver cancer detection. In the sample dataset used in the present invention, the detected performance of the screened markers and composition is optimal, which can further improve the detection accuracy on the basis of a single methylation marker and avoid the problems of false detection and missed detection. Compared with the commonly used liver cancer screening methods, the dual liver cancer molecular marker has significantly improved stability, sensitivity and accuracy, and can be used for the detection of in vitro blood samples, which is very beneficial to the popularization and promotion of early screening and early diagnosis of liver cancer.

The invention belongs to the technical field of bioinformatics, and discloses a common value evaluation method and device for tumor neoantigens, equipment and a storage medium, missense mutation analysis is performed by acquiring mutation data of a pan cancer sample, a plurality of missense mutation sites are obtained and compared with a human genome to obtain candidate mutation sites, and the candidate mutation sites are used for evaluating the common value of the tumor neoantigens. Extracting the newborn peptide fragment corresponding to each candidate mutation site, inputting the newborn peptide fragment into the prediction model, predicting the binding score of the newborn peptide fragment and the human leukocyte antigen, and calculating the common value score of each newborn peptide fragment according to the number of the newborn peptide fragments generated at the candidate mutation sites and the corresponding binding score of the newborn peptide fragment and the human leukocyte antigen; according to the method, the new peptide fragments are sorted according to the descending order of the scores, and the new antigen sequence is screened out from the sorting result, so that the new antigen value can be effectively evaluated based on the number of the new peptide fragments generated by the site and the binding scores of the corresponding new peptide fragments and the human leukocyte antigen, and the new antigen with higher adaptability is screened out.

A computer implementable system manages genetic information associated with a human genome of a target subject and displayed via a graphical user interface (GUI). The target subject genetic information is encrypted. The system compares the clinical data of the target subject with clinical data in its database to provide a first ranking of possible genetic diseases. Then the genetic information of the target subject is compared to the genetic information in the database to re-rank via a weight score evaluation based on predetermined criteria thereby providing a second ranking of possible genetic diseases. Allowing a user to decrypt a portion or portions of the encrypted target subject genome that are related to the possible genetic diseases and blocking decryption of the rest of the genome. Providing access to the decrypted portions of the target subject genome via the GUI.

A genetic prime editing screening platform to identify functional variants related to human health and disease, is configured substantially to annotate genome with nucleotide resolution with actionable disease prediction and treatment for personalized medicine.

The invention relates to the technical field of molecular auxiliary diagnosis, and discloses a specific methylation marker for auxiliary diagnosis of renal papillary cell carcinoma, the marker is cytosine which takes a human genome GRCh38.p14 Primary Assessment as a reference genome and is located in at least one CpG site in a Chr7: 99392794-99392876 region, and the marker is one or more of cytosine at the positions of Chr7: 99392813, Chr7: 99392820, Chr7: 99392831, Chr7: 99392855 and chr7: 99392871. According to the invention, CpG site cytosine in the Chr7: 99392794-99392876 region is limited as a methylation marker, so that the problems of difficult cancer species identification and high missed diagnosis rate caused by the situation that traditional renal cell carcinoma diagnosis mostly depends on imaging subjective interpretation or generalization of tumor markers are improved.

Described are methods for identifying an ASD risk gene, NHIP, and methods for determining the risk of an offspring for developing an ASD. A common structural variant disrupting the proximity of NHIP to a fetal brain enhancer was associated with NHIP expression and methylation levels and ASD risk, demonstrating a common genetic influence. NHIP is a novel environmentally-responsive ASD risk gene relevant to brain development in a previously under characterized region of the human genome.

The invention belongs to the field of molecular biology and medicine, and discloses a primer, a probe group and a detection system for detecting a single nucleotide polymorphism (SNP) molecular marker related to liver cancer susceptibility and prognosis. The SNP molecular marker rs6903C / T is located in a 3 'UTR region of an MRPL34 gene, and the expression and protein level of the MRPL34 gene are influenced due to the change of m6A modification. Through screening of more than 48,000,000 SNPs of 1161 liver cancer cases and 1353 contrast cases and verification in 3157 liver cancer cases and 4795 contrast cases, the rs6903 is found to be significantly associated with the susceptibility of the liver cancer; meanwhile, through analysis of 451 liver cancer cases and 147 liver cancer cases, the rs6903 is found to be a molecular marker for prognosis of the liver cancer. The primer disclosed by the invention is used for amplifying a gene segment containing a human genome rs6903 site; the probe is used for identifying whether cytosine nucleotide at the rs6903 site in the amplified gene segment is mutated into thymine nucleotide or not; meanwhile, the invention also provides a reaction system for detecting the rs6903 site.

Some aspects of this disclosure provide compositions, strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins capable of inducing a cytosine (C) to guanine (G) change in a nucleic acid (e.g., genomic DNA) are provided. In some embodiments, fusion proteins of a nucleic acid programmable DNA binding protein (e.g., Cas9) and nucleic acid editing proteins or protein domains, e.g., deaminase domains, polymerase domains, and / or base excision enzymes are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a nucleic acid programmable DNA binding protein (e.g., Cas9), and nucleic acid editing proteins or domains, are provided.

The present invention provides a urine simulation sample, a reference product for urothelial carcinoma, and a preparation method and application thereof. A preparation method of a urine simulation sample for urothelial carcinoma comprises the following steps: S1: preparing a urothelial carcinoma cell culture: digesting T24 cells with trypsin at a concentration of 0.15% - 0.35% v / v, and culturing to obtain a T24 cell suspension; S2: preparing free DNA of urothelial carcinoma: fragmenting the human genomic DNA standard NA12878 with 100% methylation level into free DNA with a length of 150 bp - 300 bp; S3: mixing the urothelial carcinoma cell culture obtained in step S1, the free DNA of urothelial carcinoma obtained in step S2, and a urine sample of a healthy person to obtain a urine simulation sample for urothelial carcinoma. The present invention provides a urine simulation sample and a reference product with a clear background, capable of simulating clinical samples, having low cost, being renewable and having universality.

The invention relates to the technical field of plasma free DNA methylation markers, and provides a plasma free DNA methylation marker and application thereof. The methylation marker is composed of 50 methylation regions on a human genome hg38, and the cancers comprise lung cancer, colorectal cancer, liver cancer, stomach cancer, breast cancer, esophageal cancer and pancreatic cancer. The universal DNA methylation biomarkers capable of being used for combined diagnosis of multiple cancer species are screened out, and the markers have high specificity and sensitivity to cancer samples of different clinical stages and are of great significance to early diagnosis of cancers.

The invention relates to the technical field of gynaecology and obstetrics, and discloses a model for predicting the PE risk of pregnancy in early and middle pregnancy, which comprises the following steps: collecting a sample from peripheral blood of a pregnant woman, and separating plasma; the method comprises the following steps: extracting free DNA from plasma by using a magnetic bead separation method, and performing purification and quantitative treatment; performing high-throughput sequencing on the extracted free DNA to obtain sequencing data; through bioinformatics analysis, sequencing data is compared to a human genome, and a gene sequence related to PE is identified; and on the basis of the identified biomarker, in combination with clinical data of the pregnant woman, constructing a model for predicting the PE risk. According to the method, the prediction model is constructed by combining the free DNA sequencing data and the clinical data, so that the accuracy and the stability of predicting the PE risk can be improved. And gene sequences and variations related to PE can be identified through bioinformatics analysis and genome data comparison, so that more reliable prediction information is provided.

The application discloses a single-cell mixed sample sequencing and sample splitting method based on HLA genes. The application first acquires HLA gene typing information of each sample to be mixed; secondly, single-cell mixed sample sequencing is performed on the mixed sample to obtain single-cell mixed sample sequencing results of the mixed sample; finally, based on the HLA gene typing information, the sample source of each cell is identified by calculating the expression characteristics of HLA genes in the single-cell mixed sample sequencing sequence, and sample splitting is completed. The application breaks through the technical obstacle that few-cell clinical samples cannot be subjected to single-cell sequencing, greatly improves the utilization rate of these precious samples, significantly reduces the calculation consumption of sample splitting through an efficient HLA gene sequence pseudo-alignment algorithm, improves the ability to obtain genetic information from low-coverage cells by focusing on the HLA region with the highest polymorphism in the human genome, and effectively reduces the sequencing cost of a single sample through mixed sample sequencing.

The present invention relates to the technical field of single-cell multi-omics sequencing, and discloses a method for analyzing the epigenetic characteristics of chromosomal instability (CIN) in tumor cells. The steps include: preparing single-cell RNA libraries and DNA libraries for sequencing; respectively preprocessing the DNA and RNA sequencing data, aligning them to the human genome reference sequence, identifying differentially methylated regions, performing karyotype analysis, dividing tumor cells into different subgroups, and quantifying gene expression levels; analyzing the correlations among DNA methylation differences, gene expression differences, and karyotype heterogeneity between different subgroups. The method of the present invention can simultaneously measure DNA methylation, gene expression, and karyotype of single cells, and on this basis, analyze the correlations among DNA methylation, gene expression, and karyotype heterogeneity of tumor cells, which helps to more deeply understand the mechanisms of tumorigenesis and evolution.

A method and a kit for detecting influenza A and B viruses provides a primer group that can simultaneously detect influenza A virus and influenza B virus, in which a first primer pair uses a specific genome fragment of influenza A virus as an amplification target, and a second primer pair uses a specific genome fragment of influenza B virus as an amplification target. The primer group can withstand at least 300 nanograms (ng) of human genomic DNA interference in reverse transcription polymerase chain reaction when detecting influenza A and B viruses, thereby making detection sensitivity less susceptible to interference from human genomic DNA in the sample.

A haploid modeling method based on pan-genome genetic information relates to the field of genetic engineering technology. In response to the problem of low efficiency of existing haploid modeling, this application aims to ensure the existence of "essential genes" in the human genome as much as possible through a core sequence mechanism and a sliding window mechanism. In addition, this application divides the pan-genome into multiple core windows so that a single window becomes a relatively independent individual and then parallelizes them to support highly parallel modeling, thereby improving modeling efficiency while ensuring authentic modeling.