49 results about "Missense mutation" patented technology

The present invention relates to a computer-implemented multi-module classifier method and system for providing a pathogenicity classification score of a variant of a protein of interest. The classifier comprises a sequence module based on a protein language model (PLM); a structure module based on a graph neural network (GNN); a property module; and a unified head module based on a machine learning model. The invention further relates to methods for preparing, training, and implementing the multi-module classifier system.

The invention discloses a missense mutation function effect prediction model construction method and a prediction method, and relates to the technical field of biological information. According to the method, on the basis of pathogenic and benign missense mutation data, various molecular phenotypic characteristics are enriched and annotated through statistical indexes, and a machine learning model for mutation function effect prediction is constructed. The model fuses feature information of a plurality of molecular levels, comprises comprehensive evaluation indexes of a residual base level, a mutation level and a protein level, and is trained and optimized based on a random forest algorithm. The method not only can accurately predict pathogenic mutation, but also shows excellent performance in recognition of cancer-driven missense mutation, has good generalization ability and biological interpretability, and can provide solid technical support for pathogenicity and carcinogenicity recognition of missense mutation and molecular mechanism research of missense mutation.

The invention discloses application of an NPFFR2 gene SNP site in judgment of dairy cow hysteritis resistance, and belongs to the technical field of livestock and poultry molecular biology, the SNP site is rs110326785, and the site generates Ggt; the metritis resistance of a dairy cow individual with the genotype of GG at the site is obviously higher than that of dairy cow individuals with the genotypes of GA and AA. The mutation of the SNP site rs110326785 is missense mutation, so that glutamic acid at the 406th site of an amino acid sequence coded by NPFFR2 mutates into lysine, when the genotype of the site is GG, the dairy cow metritis resistance is the highest, and the SNP site can be used for screening and identifying dairy cows with high metritis resistance, so that dairy cow individuals with high metritis resistance are selected for cattle herd optimization and auxiliary breeding.

The invention relates to the technical field of biological gene mutation prediction, in particular to a multi-omics feature-based missense mutation function classification method and system. The classification method comprises the following steps: S1, collecting a multi-omics comprehensive feature set related to missense mutation; s2, constructing a heterogeneous graph; s3, learning a meta-path-based weight of each node in the heterogeneous graph; s4, calculating weights of different meta-paths by using attention of a semantic level; s5, performing weighted summation on the node weight and the meta-path weight to obtain final embedding representation of each node; s6, training to obtain a multi-omics feature-based missense mutation function classification model; and S7, outputting a prediction score based on the multi-omics feature missense mutation function classification model, and dividing missense mutation according to the prediction score. According to the method, the heterogeneous graph is constructed by utilizing multiple omics characteristics, and the relationship between biological entities is explicitly modeled, so that GOF and LOF mutations are distinguished more accurately.

The invention relates to the technical field of tumor vaccines, and provides a novel mRNA (messenger Ribonucleic Acid) tumor vaccine for treating mouse liver cancer, which is prepared by the following steps: S1, specific neoantigen prediction: carrying out bioinformatics analysis on a next-generation sequencing database of tumor patients in the hospital, and selecting tumor specific neoantigens through the following steps; s11, low-quality readings are removed through a filtering step; s12, detecting single nucleotide variation by using a Mutect method and a VarScan method; s13, annotating missense mutation by using ANNOVAR software; in-vivo and in-vitro experiments prove that the vaccine has a remarkable anti-tumor effect, is designed and synthesized aiming at a newly screened new antigen mutation sequence and has high specificity and pertinence, and experimental results show that the vaccine can remarkably improve immune response of specific CTLs cells, induce T cell response of new antigen specificity, and has a good anti-tumor effect in a tumor-bearing mouse model. The vaccine has a remarkable inhibiting effect on tumor growth, and the problems in the prior art are solved through the technical scheme.

Mouse models of obesity associated with human MC4R missense mutations are provided. Human mutations introduced with CRISPR / Cas9 into the mouse MC4R gene lead to an severely obese mouse phenotype in mice with a heterozygous genotype.

The present invention generally relates to tRNA-based effector molecules for use in inserting missense mutations into the open reading frame (ORF) of a gene, e.g., for the treatment of repetitive sequence amplification diseases.

This invention discloses a method for directed evolution of antibiotic-resistant Escherichia coli strains based on cytidine deaminase, belonging to the field of microbial directed evolution and genetic engineering technology. This method uses E. coli as the host, introducing a recombinant plasmid expressing an optimized double-stranded cytidine deaminase mutant. Utilizing the low toxicity and high mutagenicity of this mutant, continuous passage evolution is carried out under gradient concentrations of aminoglycoside antibiotics (kanamycin and streptomycin). Combined with whole-genome sequencing, molecular docking, and reverse genetics verification, the A145T missense mutation in the wcaE gene is identified as the core functional site. This invention overcomes the shortcomings of traditional spontaneous and chemical mutagenesis, which suffer from low efficiency and significant strain damage. The mutation type is controllable, the evolutionary cycle is short, and the obtained engineered strains can tolerate up to 300 mg / L kanamycin while exhibiting streptomycin cross-resistance, and the genetic stability of the tolerance trait is strong. This method is simple, highly reproducible, and suitable for industrial breeding of stress-resistant E. coli, and can be widely applied in antibiotic fermentation, industrial microbial culture, and other scenarios.

The invention relates to the technical field of agricultural breeding, and discloses a molecular marker related to egg shell color and application of the molecular marker, the SNP molecular marker corresponds to the 18378867 site from the 5'terminal on a chicken reference genome GRCg6a 6 # chromosome published in an Ensembl gene browser database, and the base of the site is C / T and is missense mutation on an ABCG2 gene. The SNP molecular marker is related to the egg shell color, is a new molecular marker, can accelerate the breeding progress of the character by detecting the genotype of the locus of a chicken individual to be determined and performing early selection on the chicken with the dominant genotype, and has great application value and economic benefit.

The invention discloses an SNP (Single Nucleotide Polymorphism) molecular marker related to a pig body length character and application, and belongs to the technical field of biology. The SNP molecular marker is located on a pig X chromosome, and an SNP site is located at the 467th basic group of a pig BHLHB9 gene coding region (A in ATG in the coding region is 1); the basic group of the SNP site is C / T missense mutation. The SNP molecular marker related to the pig body length character is disclosed for the first time, is used for distinguishing individuals with medium and short body lengths and individuals with long body lengths, is suitable for domestic pig breeds and foreign pig breeds, and is wide in pig breed application range. The method for detecting the genotype of the SNP molecular marker disclosed by the invention can be used for quickly and effectively predicting the body length of a pig in an early stage at low cost, has a wide application prospect in the aspect of improvement of a pig variety strain, and can obtain an excellent economic value.

The present invention provides a method of slowing the progression of ER + breast cancer in a patient comprising administering to the patient an effective amount of lasofoxifene or a pharmaceutically acceptable salt thereof and an effective amount of a CDK4 / 6 inhibitor (CDK4 / 6i) wherein breast cancer: (i) is estrogen receptor positive (ER +); (ii) having at least one function-acquired missense mutation within the ligand binding domain (LBD) of the estrogen receptor 1 (ESR1) gene; and (iii) have progressed and / or have oncogenic mutations in genes other than ESR1 during previous treatment with a CDK4 / 6 inhibitor.

To provide: methods of treating a patient diagnosed with or suspected of having Fabry disease; and methods of enhancing α-GalA in a patient diagnosed with or suspected of having Fabry disease.SOLUTION: There is provided a method comprising administering to a patient a therapeutically effective dose of a pharmacological chaperone for α-GalA, wherein the patient has a missense mutation in a nucleic acid sequence encoding α-GalA.SELECTED DRAWING: None

To provide new plants exhibiting improved resistance to nematodes, seeds and parts of the plants, methods of making and using such seeds and plants, and new SmD1 alleles that result in modified SmD1 proteins associated with such improved resistance to nematodes.SOLUTION: Provided are plants comprising SmD1 alleles encoding SmD1 proteins having at least 90% amino acid sequence identity to a particular sequence, wherein the SmD1 proteins comprise missense mutations resulting in modified SmD1 proteins that confer enhanced nematode resistance.SELECTED DRAWING: None

In general, the current disclosure relates to the tRNAs that encode for one amino acid but are covalently linked to a different amino acid. The tRNAs can correct missense mutations by providing a different amino acid during protein synthesis. Such tRNAs can be used to correct disease-causing missense mutations.

The invention provides a novel human distal bile duct cancer cell line with TP53 missense mutation and application, the novel human distal bile duct cancer cell line CBC3T-3 is established, the cell line is preserved in the China Center for Type Culture Collection (the preservation number is CCTCC NO: C202555), the uniqueness and stability of the cell line are proved through STR typing and karyotype analysis, and the TP53 missense mutation novel human distal bile duct cancer cell line has the advantages that the TP53 missense mutation novel human distal bile duct cancer cell line CBC3T-3 can be used for preparing the TP53 missense mutation novel human distal bile duct cancer cell line CBC3T-3; and a plurality of driver gene mutations including TP53 missense mutation are carried. The CBC3T-3 has strong proliferation, invasion and migration capabilities, has high tumor formation rate in immunodeficient mice, is resistant to cis-platinum and sensitive to paclitaxel and gemcitabine, and provides an experimental basis for selection of clinical chemotherapy regimens. According to the model, the TP53 missense mutation type distal bile duct cancer in-vitro model is successfully established, and a key experimental platform is provided for deeply researching the drug resistance mechanism of the TP53 missense mutation type distal bile duct cancer and developing an individualized treatment strategy aiming at the subtype of the TP53 missense mutation type distal bile duct cancer.

The disclosure provides methods for treating estrogen receptor positive (ER+) cancer in a patient who has progressed on an aromatase inhibitor. Of particular interest are ER+ cancers that do not harbor a gain of function missense mutation within the ligand binding domain (LBD) of the Estrogen Receptor 1 (ESR1) gene. The provided methods involve the administration of an effective amount of lasofoxifene, a pharmaceutically acceptable salt, prodrug or functional derivative thereof.

The application relates to the technical field of agricultural breeding, and discloses a molecular marker related to eggshell color and application thereof. The SNP molecular marker corresponds to a site of 18378867 from a 5' end on a chromosome 6 of a chicken reference genome GRCg6a published in an Ensembl genome browser database, the base of the site is C / T, and the site is a missense mutation on an ABCG2 gene. The SNP molecular marker related to the eggshell color is a new molecular marker. By detecting the genotype of the site of a chicken individual to be determined, early selection is carried out on the chicken with an advantageous genotype, the breeding progress of the trait can be accelerated, and the application has great application value and economic benefits.

A gene signature for evaluating likely sensitivity of a cancer cell to treatment with inhibitors of Werner syndrome RecQ helicase (WRN) is provided. For cancer cells that have microsatellite instability (MSI) and / or mismatch repair deficiency (dMMR), sensitivity to treatment with a WRN inhibitor is likely if the cancer cell has a loss of function mutation in at least two of KMT2D, ARID1A or RAD50, or if the cancer cell has a loss of function mutation in ARID1A only, without loss of function mutations in KMT2D and RAD50. Cancer cells that are MSI and / or dMMR in which both ARID1A and at least one of KMT2D and RAD50 are wild type or have only missense mutations are unlikely to be sensitive to treatment with WRN inhibitors.

The invention provides an anti-tumor drug cell screening model establishment method based on a TBR1 site-directed mutant and application, and belongs to the technical field of biological medicine. By analyzing data of patients with medullary blastoma (MB) in children hospital of Nanjing Medical University and clinical patients with MB in EGA database, it is found that the proportion of Group 4 subtype MB is the highest, and TBR1 mutation specifically exists in Group 4 subtype MB; a mutation spectrum of TBR1 in Group 4 subtype MB clinical patient data is analyzed, a result shows that mutation is missense mutation, mutation sites are all concentrated in a T-box structural domain of TBR1, and a TBR1-G275 site is high-frequency mutation; the method comprises the following steps: designing a site 275 of a pegRNA targeted TBR1 T-box region by using a CRISPR-Cas9-based PE (Polyethylene) technology, carrying out site-directed mutagenesis on TBR1 in a Group 4 subtype D283 cell line on a genome level, and successfully constructing the Group 4 subtype MB cell model with TBR1-G275C mutation by using a method of drug screening, monoclonal culture and final sequencing verification.

The application provides a method and system for predicting the influence of missense mutations on clinical drug efficacy based on deep learning, comprising the following steps: S1, obtaining and preprocessing drug and mutant protein sequence data sets; S2, normalizing drug input data; S3, normalizing mutant protein sequence input data; S4, building a deep learning model according to the normalized data, and outputting a prediction classification. The application can predict the influence of mutations on clinical drug efficacy only using the structure attributes of drugs and mutant protein sequences. Since the application uses a relatively small feature dimension, it supports high-throughput mutation drug efficacy prediction with low computational overhead. The application can use a deep learning method to predict the influence of mutations on clinical drug use with high precision while maintaining interpretability, and the input features do not include clinical drug information and crystal structure determination experimental information.

The invention discloses application of an ALPK2 gene missense mutation marker in breeding of pigs with dominant production traits, and belongs to the technical field of molecular genetics and livestock breeding. By detecting ALPK2 gene mutation and screening individuals carrying mutation rs327271406 as a GG genotype, individuals with excellent growth traits (fast growth and high meat production performance) of European pig breeds can be rapidly screened out, the breeding period is shortened, the meat production efficiency of pig herds is improved, the breeding cost is reduced, the method is used for early screening of pig breeds with fast growth and high meat yield, high-quality pig herd breeding is accelerated, and the economic benefit is increased. The method evaluates the pig muscle development potential, guides molecular marker assisted breeding, and is especially used for commercialized lean type pig production.

Provided are RNAi involving siRNA, shRNA or antisense oligonucleotide (ASO) that reduce the expression of toxic KIF1A alleles, thereby reducing the production of mutant KIF1A, for use in the treatment of KAND. Also provided are RNA targeting oligonucleotides that reduce the expression of toxic KIF1A alleles herein incorporate sequences that target common benign single nucleotide polymorphisms (SNPs) that are cis present with one or more pathogenic KIF1A mutations.

The application belongs to the technical field of gene diagnosis, and discloses a new pathogenic gene CYLC1 of sperm head deformity and a mutation detection reagent thereof; the new pathogenic gene CYLC1 of sperm head deformity is used as a candidate gene diagnosis object of sperm head deformity, and four homozygous missense mutations thereof are c.1157A>C / p.N386T, c.1377G>T / p.K459N, c.1402T>G / p.S468A and c.1834T>A / p.C612S. The application can use the detection reagent to perform simple, fast and accurate gene diagnosis on sperm head deformity patients, and is also helpful for understanding pathogenesis, genetic counseling, prenatal diagnosis and gene therapy. The application can also use the established Cylc1 gene knockout mouse model to reveal the role and mechanism of Calicin-1 protein on sperm acrosome anchoring and head development of mammals.

The invention discloses application of a reagent for detecting SCN2B and / or SCN4B gene mutation in preparation of a hereditary arrhythmia detection product. According to the present invention, through the dual detection system combining whole exon sequencing with Sanger sequencing verification, the accurate capture of the pathogenic mutation such as SCN2B-R28Q / Y69H / P210L and SCN4B-T211M is achieved, and the problem that only SCN5A is determined as the main pathogenic gene in the clinical diagnosis of J wave syndrome (JWS) at present, and the gene detection of about 70-80% of patients is negative is solved. Wherein the three missense mutations of the SCN2B and the SCN4B-T211M variation are reported in the JWS for the first time, and the SCN4B is clear as the JWS pathogenic gene for the first time, so that the pathogenic gene spectrum of the JWS is obviously expanded. A detection product developed on the basis of the method can realize early accurate diagnosis, provide personalized risk assessment (such as sudden death early warning induced by fever) for patients, guide genetic screening of family members and remarkably improve clinical diagnosis and treatment efficiency.

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with biallelic missense mutations in otoferlin (OTOE), by way of OTOE gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOE isoform 5 protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOE isoform 5 protein. These vectors can be used to increase the expression of OTOE in a subject, such as a human subject suffering from sensorineural hearing loss.

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.

The application discloses application of a reagent for detecting SCN2B and / or SCN4B gene mutation in preparation of a genetic arrhythmia detection product. Through a double detection system of whole exon sequencing combined with Sanger sequencing verification, the application realizes accurate capture of pathogenic mutations such as SCN2B-R28Q / Y69H / P210L and SCN4B-T211M, and solves the difficulty that only SCN5A is confirmed as a main pathogenic gene in the current clinical diagnosis of J wave syndrome (JWS), and about 70%-80% of patients have gene detection negative. The three missense mutations of SCN2B and the SCN4B-T211M variation are reported for the first time in JWS, and SCN4B is confirmed as a pathogenic gene of JWS for the first time, which significantly expands the pathogenic gene spectrum of JWS. The detection product developed based on this can realize early accurate diagnosis, provide personalized risk assessment (such as early warning of sudden death induced by fever) for patients, and guide genetic screening of family members, and significantly improves the clinical diagnosis and treatment efficiency.

The application discloses an SCN5A mutant gene, wherein a base G at a genomic position chr3:38607917 is mutated into a base A, or a base G at a genomic position chr3:38620923 is mutated into a base T, with reference to a gene sequence GRCh37. The hybrid missense mutation of the base G at the genomic position chr3:38607917 into the base A and / or the hybrid missense mutation of the base G at the genomic position chr3:38620923 into the base T can distinguish a supraventricular syndrome patient from normal people, and can also be used as a biomarker for assisting clinical diagnosis of the supraventricular syndrome. The primers and the kit provided by the application provide a new drug target for human beings to conquer the supraventricular syndrome, and promote the research and development of innovative drugs.

The present invention relates to a therapeutic oligonucleotide for use in treating a disease in a subject that is associated with or caused by a missense, nonsense or in-frame indel mutation in a gene of the genome of the subject, wherein the therapeutic oligonucleotide is capable of specifically hybridizing to the 5'-splice site, the 3'-splice site or an exonic splicing enhancer (ESE) of an out-of- frame exon in the gene with the missense, nonsense or in-frame indel mutation, thereby causing skipping of the out-of-frame exon.

Provided herein are methods and systems for targeted gene disruption (knock-out, missense mutation) and targeted gene knock-in in mammalian cells using base editors and guide RNAs (gRNAs) designed to target splice acceptor-splice donor sites. Also provided herein are universally acceptable genetically engineered cells comprising targeted disruptions in immunotherapy-related genes and comprising a CAR / TCR for therapeutic applications.