112 results about "Specific mutation" patented technology

The invention discloses a screening method of a gene region set for detecting small residual focuses of ovarian cancer, the gene region set and a detection system of the gene region set, and belongs to the technical field of gene molecular diagnosis. According to the method, a preoperative blood sample, an intraoperative multipoint tumor tissue sample and postoperative daily peritoneal drainage liquid of an ovarian cancer patient on the first to sixth days are taken as detection samples, a novel ovarian cancer nuclear genome hot spot region screening method is developed, a gene region for ovarian cancer tumor DNA detection is constructed, and tumor tissue mutation information is taken as a tracing basis, so that an ovarian cancer tumor DNA detection result is obtained. The characteristics of tumor tissue specific mutation in the free DNA of the peritoneal drainage liquid are analyzed, and the purpose of detecting the free tumor DNA of the peritoneal drainage liquid is achieved. The method can be applied to the postoperative residual focus detection of the ovarian cancer patient, can sensitively and accurately evaluate the postoperative residual focus state of the patient at an early stage, and provides timely prognosis judgment basis for clinic, so as to support the adjustment of clinical decisions.

The invention discloses a 4-hydroxyphenylacetic acid-3-hydroxylase mutant with improved activity and application thereof, the 4-hydroxyphenylacetic acid-3-hydroxylase mutant is obtained by mutating wild type 4HPA3H enzyme from Escherichia coli, the amino acid sequence of the wild type 4HPA3H enzyme is as shown in SEQ ID No.1, and the amino acid sequence is specifically mutated into any one of the following: (1) M205F; and (2) T398S. According to the present invention, the whole-cell catalysis activity of the 4-hydroxyphenylacetic acid-3-hydroxylase mutant, the M205F mutant and the T398S mutant on the p-hydroxyphenyllactic acid is improved by 1.70 times and 1.24 times compared with the WT;

The invention belongs to the technical field of biomedicine, and particularly relates to tumor neoantigen polypeptide based on EGFR gene mutation and application of the tumor neoantigen polypeptide. According to the effective method for predicting and screening the tumor neoantigen by using the tumor neoantigen prediction platform, the specific mutation of tumor tissues is obtained, and the neoantigen polypeptide with high immunogenicity, high affinity and high activation effect is more accurately predicted; the screened new antigen polypeptide makes up the blank of individualized antigen peptide in treatment of lung cancer NSCLC patients with EGFR-L858R somatic mutation, can be synthesized in a large scale, is used for subsequent standardized and individualized immunotherapy of EGFR-L858R mutation tumor patients, and has a good clinical application prospect.

The purpose of the present invention is to provide: a protein that has an α1,2-fucosyltransferase activity and has excellent LNFPI productivity; and a method for producing LNFPI. The present invention provides a protein that has an activity to transfer a fucosyl group into lacto-N-tetraose (LNT) and has a specific mutation introduced therein (excluding a protein having a property such that an amino acid sequence for the protein to which a mutation is not introduced yet and an amino acid sequence for the protein to which the mutation has been introduced are the same as each other).

The present invention provides a computer-implemented method for predicting the treatment response of a subject having a lung cancer to an immune checkpoint inhibitor (CPI) therapy, the method comprising: providing a mutation profile of the subject, said profile comprising the presence or absence of cancer-specific mutations at one or more locations in at least five genes selected from the group consisting of: NF1, STK11, TSC2, BRCA2, BRAF, STAG2, U2AF1, BRIP1, PDGFRA, CTNNA1, PDK1, FGF10, and FLT1; analysing the mutation profile to classify the profile as matching the mutation profile of a response signature or a resistance signature, wherein the subject is predicted to be likely to respond to the CPI therapy if the mutation profile for the subject is classified as matching the mutation profile of the response signature and is predicted to be likely not to respond to the CPI therapy if the mutation profile for the subject is classified as matching the mutation profile of the resistance signature. Also provided are related methods and systems for predicting the treatment response of a subject having a lung cancer to an immune checkpoint inhibitor (CPI) therapy.

The present disclosure provides methods of determining whether a tumour-specific mutation is likely to be clonal in a subject. The method comprise determining, by a processor, a metric indicative of the probability that the mutation is clonal by combining evidence from sequence data obtained from the subject and an indication of whether the mutation is associated with one or more predetermined mutational signatures. The methods may be used to identify clonal mutations and clonal neoantigens in a subject, and to design immunotherapies that target clonal neoantigens. Related methods, systems and products are also described.

The present invention provides a computer-implemented method for estimating the cancer cell fraction (CCF) of at least one tumour-specific mutation in a subject. Also provided are related methods for monitoring the clonal dynamics of a tumour, monitoring a treatment of the tumour and methods for treating a subject having a cancer, as well as systems for implementing the methods of the invention.

The invention relates to novel DNA polymerases of the polX family, and in particular Terminal deoxynucleotidyl Transferase (TdT) variants comprising specific mutations or substitutions, and to their uses.

The invention states to a novel DNA polymerase of the polX family, in particular a Terminal deoxynucleotidyl Transferase (TdT) variants comprising specific mutations or substitutions and their uses.

The invention states to a novel DNA polymerase of the polX family, in particular a Terminal deoxynucleotidyl Transferase (TdT) variants comprising specific mutations or substitutions and their uses.

Disclosed are methods of isolating T cells having antigenic specificity for a mutated p53 amino acid sequence encoded by a cancer-specific p53 mutation, the method comprising: inducing autologous APCs of the patient to present the mutated p53 amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated p53 amino acid sequence; and selecting the autologous T cells. Also disclosed are related methods of preparing a population of cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

The disclosed embodiments concern methods for determining sequences of interest using targeted unique molecular index (TUMI) sequences that are uniquely associated with individual polynucleotide fragments in plants, such as those present in a transgenic event, a site-specific mutation or a wild type variant. System, apparatus, and computer program products are also provided for determining a sequence of interest implementing the methods disclosed.

A new technique for improving the secretion production of a heterologous protein by a coryneform bacterium is developed, and thus a method for the secretion production of a heterologous protein is provided. A coryneform bacterium having a secretion production ability of a heterologous protein and modified to maintain a phoS gene having a specific mutation is cultured to produce a heterologous protein by secretion.

Genetically modified zebrafish, in which mutation combinations frequently identified in human AML are stably expressed in the stem cell population of the fish, are provided. The combination of mutations result in morphologic, cytochemical and molecular changes of its blood cells that are remarkably similar to those in human AML. The zebrafish model provides a foundation for the study of AML initiation and progression and a high throughput in vivo drug screening platform to identify personalized therapies for AML based on specific mutation combinations. The method of drug screening includes contacting embryos or adult fish containing mutations as disclosed herein, with a test agent, at test concentrations and test intervals to determine the therapeutic effect if any, of the test agent.

This disclosure relates to a technique for identifying tumor-specific mutations through integrated analysis of next-generation sequencing data using machine learning models. In certain embodiments, a computer implementation method is provided, comprising: generating sequence reads from one or more samples collected from the same patient; generating variant calling files by analyzing the sequence reads corresponding to each of the one or more samples; generating a list of candidate somatic variants by comparing the variant calling files; generating a score for each of the candidate somatic variants in the list of candidate somatic variants using a classification machine learning model, wherein the score is generated based on a plurality of classifications generated by the classification machine learning model; determining the ctDNA status for the patient based on the score, wherein the ctDNA status is either positive or negative; and generating a report providing the ctDNA status for the patient.

Provided herein are methods and compositions related to the finding that specific mutations in nonstructural proteins of self-replicating RNA molecules including RNA replicons, such as Sindbis RNA replicons or Venezuelan equine encephalitis (VEE) replicons, can stabilize the longevity of the RNA replicon and can stabilize the expression of the cargo proteins encoded by the self-replicating RNA molecule or RNA replicon. Also disclosed herein are compositions and methods directed to the discovery that certain viral proteins, including viral proteins that repress internal cellular innate immunity, can stabilize the payload expression and replication of the replicons. Technologies provided herein provide stabilization mechanisms that can improve vaccines, gene therapies, and / or other gene delivery methods.

This invention discloses a sequencing technique for enriching mutations after library construction. The co-priming amplification (Co-PCR) technique of this invention couples a mutation probe to a short P5 / P7 primer. This short primer has a low melting temperature (Tm) and cannot hybridize and amplify on its own at the reaction temperature. Only when the mutation probe hybridizes to the mutation site can it assist the coupled short P5 / P7 primer in hybridizing to the adjacent P5 / P7 sequence at the end of the pre-library, initiating amplification. Therefore, this Co-PCR technique not only amplifies a specific mutation in a specified gene but also amplifies from both ends of the original pre-library, replicating the complete sequence information of the pre-library, including sequencing adapters, indexes, and sequencing primers. The amplified products can be directly sequenced after purification. By optimizing the co-primers, Co-PCR enrichment amplification of five sites in the pre-library was achieved, resulting in nearly 100-fold enrichment.

The invention relates to the technical field of gene detection, in particular to a probe composition and a kit for screening various genetic disease related gene mutations and a preparation method of the probe composition and the kit. The hereditary diseases comprise 23 hereditary diseases such as citrullinemia type, hepatolenticular degeneration, 21-hydroxylase deficiency, progressive pseudohypertrophy muscular dystrophy, fragile X syndrome, Friedreich ataxia, glycogen accumulation disease type II, Gaucher disease, autosomal recessive deafness type 1A, Fabry disease, alpha-thalassemia, beta-thalassemia and the like. The probe composition disclosed by the invention can be used for simultaneously screening the specific mutation types of the various genetic disease related genes, and is more accurate, comprehensive, convenient, high in detection efficiency, simple and economical compared with the traditional screening.

The invention discloses a construction method and application of a basic group editor of industrial bacteria of cephalosporium acremonium based on CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9), and belongs to the field of gene engineering. The cephalosporium acremonium industrial bacterium base editor provided by the invention can be used for specific mutation of a specific site of the DNA level of the cephalosporium acremonium industrial bacterium. The cytosine base editor CBE constructed by the invention is a plasmid comprising a fusion protein A and an sgRNA expression element. The base editor CBE can successfully mediate C.G-T.A, is suitable for the base editor of the high-yield CPC cephalosporium acremonium industrial bacteria, utilizes the protoplast, is high in conversion efficiency, can mediate specific site mutation in the cephalosporium acremonium industrial bacteria, and has application value.

The present disclosure provides methods of introducing site-specific mutations in a target cell and methods of determining efficacy of enzymes capable of introducing site-specific mutations. The present disclosure also provides methods of providing a bi-allelic sequence integration, methods of integrating of a sequence of interest into a locus in a genome of a cell, and methods of introducing a stable episomal vector in a cell. The present disclosure further provides methods of generating a human cell that is resistant to diphtheria toxin.

The present invention belongs to the technical field of molecular biology, and specifically relates to a xylanase XynZT-2 mutant and its application. The xylanase XynZT-2 mutant is obtained by site-directed mutagenesis of the xylanase XynZT-2 with the amino acid sequence shown in SEQ ID No. 2. The specific mutation sites are as follows: T28I, A33V, M97L, A102C, S148T, A238G, S239P, M241L, T287S or I291V. The optimal temperature and optimal pH of 10 xylanase XynZT-2 mutants have changed, and the obtained xylanase XynZT-2 mutants show application value in the fields of pulp brewing, bioenergy, food manufacturing, etc.

A method of treating a subject having been diagnosed as having cancer with an immunotherapy is described. The method comprises targeting one or more clonal neoantigens selected using a method comprising determining whether a tumour-specific mutation is likely to be clonal in a subject. The method comprises providing sequence data from one or more samples from the subject comprising tumour genetic material, the sequence data comprising for each of the one or more samples, and determining the likelihood that the tumour-specific mutation is clonal as a posterior probability depending on: a prior probability of the mutation being clonal, and the probabilities of observing the sequence data if the tumour-specific mutation is (i) clonal and (ii) non-clonal, in view of a tumour fraction for each of the one or more samples and one or more candidate joint genotypes.

The present technology relates to methods, computing devices, and systems for predicting the fitness of mutant p53 based on the loss of transcription factor function and immunogenicity of a particular TP53 mutation. The fitness of mutant p53 may be used to determine whether a patient will benefit from a particular anti-cancer therapy such as immune checkpoint inhibitor therapy, adoptive T-cell therapy, or prophylactic cancer vaccine therapy.

This invention discloses the application of the VDAC2 gene or VDAC2 protein as a target in screening drugs for the treatment of retinitis pigmentosa, relating to the field of biomedical technology. The drug is one that reduces the expression level of the VDAC2 gene or inhibits the expression level or activity of the VDAC2 protein; the CDS sequence of the VDAC2 gene is shown in SEQ ID NO.1. This invention uses a rod cell-specific promoter to inhibit VDAC2 expression, which can significantly improve the survival rate of local photoreceptor cells. This method intervenes in the early stages of the disease, conforming to the natural course of RP. It strengthens the function of rod cells before a large number of photoreceptor cells die, delaying their degenerative process and indirectly protecting cone cells, thereby prolonging the patient's effective visual retention time. This overcomes the shortcomings of existing gene therapies, which are mainly applicable to late-stage or specific mutation types, and provides a therapeutic basis for retinitis pigmentosa.

The invention belongs to the technical field of agricultural biology, and particularly discloses a grape germplasm innovation method based on X-ray gradient mutagenesis and an LD50 precise prediction model, and the method comprises the following steps: selecting an annual grape branch for vernalization treatment, and trimming the annual grape branch into a single-bud stem segment; setting an irradiation time gradient, accurately calculating an LD50 value through a cubic spline interpolation model, and carrying out X-ray irradiation on the single-bud stem segment according to the LD50 value; after irradiation, performing cutting and liquid paraffin sealing, and then performing cuttage, potting and field planting treatment; performing secondary vernalization on mutagenesis plant branches, trimming the mutagenesis plant branches into single-bud stem segments, collecting tender leaves after cutting survival, extracting genome DNA, performing whole genome sequencing, and accurately distinguishing mutagenesis specific variation and natural variation. By establishing a complete technical system of standardized vernalization, gradient irradiation, LD50 accurate calculation and whole genome verification, the problems of inaccurate irradiation parameters, nonstandard material treatment, low mutation screening accuracy and the like in the prior art are solved.

The invention belongs to the field of software testing, and relates to a TypeScript compiler defect detection method based on variation and difference testing. According to the method, firstly, a grammar program data set containing general grammar features and specific grammar features is constructed by means of a Githhub open source community and a large language model, and a group of algorithm sets containing general mutation algorithms and type-specific mutation algorithms are designed to perform random mutation on programs in the grammar program data set; and inputting the obtained abrupt program data set into different versions of TypeScript compilers for differential testing, analyzing in combination with an execution result of Node.js, and judging whether the compiler has defects or not according to six defined conditions. A code complexity representation method is provided, six different indexes are used for measuring the code complexity of the mutation program, and the mutation program with the improved code complexity is added into a grammar program data set to continuously enrich the diversity of the mutation program.

To provide new Fc domains that have an increased serum half life by enhanced pH-dependent binding to FcRn.SOLUTION: In some aspects of the present invention, Fc domain variants are provided which display enhanced pH-dependent affinity for FcRn. In some aspects of the present invention, methods are provided for isolating antibody Fc domains that display enhanced affinity at acidic pH and pH selectivity for FcRn. In another aspect of the present invention, specific mutations and combinations of mutations in IgG1 Fc domains are provided that can result in pH-selective binding and / or increased affinity to FcRn.SELECTED DRAWING: None

The application provides a pyroglutamic acid transaminase mutant and application thereof, the mutant is obtained by mutation on the basis of wild-type pyroglutamic acid transaminase, and specific mutation includes at least one of the following sites: (1) the 13th isoleucine is mutated into arginine; (2) the 35th valine is mutated into arginine; (3) the 183rd asparagine is mutated into aspartic acid; and the mutant is suitable for industrial enzymatic production of L-aspartic acid and the process of amino acids taking L-aspartic acid as a precursor; especially, the I13R / V35R / N183D mutant obtained by modification has high positive catalytic activity and strict direction selectivity, and completely loses the reverse reaction activity of decomposing L-aspartic acid; the mutant is overexpressed with phosphoenolpyruvate carboxylase in L-threonine production strain THRS-6, and a high-efficiency L-threonine synthesis metabolic pathway is constructed, and the yield of L-threonine is significantly improved when glucose is used as a substrate.

The invention relates to norcoclaurine synthases and substrate binding sites having one or more site-specific mutation which increase the activity, when compared to the wild type synthase, of the condensation of 4-HPAA and dopamine to (S)-norcoclaurine and / or 3,4-DhPAA and dopamine to (S)-norlaudanosoline. The inventors both identified specific mutations corresponding to at position 73, 75, 77, 82, 99, 114, 141, 142, 147, 152, 174 and / or 178 in the count according to SEQ ID No: 1, and sites corresponding to the binding domains defined in SEQ IN NO: 4 and 5, where the mutated increase of the activity may be positioned within these norcoclaurine synthases. These domains are conserved regions.

The invention provides a molecular marker primer and a kit for identifying sex of brachymystax lenok tsinlingensis and application of the molecular marker primer and the kit, and belongs to the technical field of sex identification of salmonidae fishes. Through comparative analysis of genomes of male and female brachymystax lenok tsinlingensis individuals, it is found that the male brachymystax lenok tsinlingensis has two specific mutation sites, and then two pairs of primers are designed according to flanking areas of the two mutation sequences and are 617-F1 / R1 and 556-F1 / R1 respectively. Each primer can be used independently to identify the gender of brachymystax lenok tsinlingensis, and the primer has the advantages of stable, accurate and reliable result. The molecular marker primer disclosed by the invention can be used for identifying the gender of the brachymystax lenok tsinlingensis and has important significance on the development of genetic breeding work of the brachymystax lenok tsinlingensis.