29 results about "Pathogenic mutation" patented technology

The invention belongs to the technical field of medical software development, and particularly relates to a plateau newborn inherited metabolic disease screening system, a computer readable storage medium and application of the plateau newborn inherited metabolic disease screening system. According to the screening system, an altitude hierarchical multi-level reference value database based on a local healthy newborn queue is established, and the problem that the false positive rate of a plain area screening model in a plateau area is too high is solved by fitting an altitude metabolism marker reference median and a standard deviation curve. By designing a'biochemical primary screening-risk scoring-targeted sequencing automatic triggering 'three-level joint control data processing flow, targeted sequencing guided by a crowd specific pathogenic mutation library is started only when the biochemical risk is high, unnecessary whole genome sequencing is avoided, and the screening cost is remarkably reduced. The system can continuously iterate a reference curve and a risk threshold value according to definite diagnosis data, and closed-loop dynamic optimization from sample collection to report generation is achieved. The method has plateau adaptability, crowd specificity and cost controllability, and has a good clinical application prospect.

A duchenne muscular dystrophy-related exonic splicing enhancer, sgRNA and gene editing tool can be applied in the preparation of drugs for treating duchenne muscular dystrophy. The gene editing tool designed on the basis of cytosine deaminase AID mutants and Cas9 mutants can perform site-specific modification on a mammalian genome by using an adeno-associated virus (AAV) as a vector. By optimizing an encoding nucleic acid sequence and an element composition structure of the editing tool, site-specific targeted modification of mammalian genetic material DNA can be efficiently achieved; and by performing targeted genetic manipulation on the nucleic acid sequence carrying disease mutations, a pathogenic mutation cannot be retained in a mature protein amino acid sequence or the pathogenic mutation cannot perform its function, so that the purpose of treating various gene mutation type genetic rare diseases is achieved, and the advantages of high efficiency, safety and stability are achieved.

The application relates to the technical field of gene sequencing data processing and bioinformation analysis, in particular to a Web-based whole-exome sequencing tumor gene mutation detection visual analysis method and system. The system collects user sequencing data and a reference genome version through a Web interactive interface; a program is called to perform quality control cleaning and evaluation on the data, and a visual report is generated; sequence alignment is completed based on the reference genome, and a variation site is identified through algorithm iteration; biological annotation of the variation is combined with a database, a candidate pathogenic mutation set is screened out in multiple levels according to a strategy, the candidate set is projected to a visual interface, a site state is confirmed or removed in response to a manual checking instruction, and a final gene mutation detection report is generated. The application greatly simplifies the whole-exome sequencing data processing procedure, makes it easy for clinical doctors or researchers without bioinformation background to start, and improves the popularization rate and work efficiency of tumor gene detection work.

Methods and systems for predicting the pathogenicity of variant sequences detected in a sample from a subject are described. The disclosed methods may comprise, for example, receiving sequence read data for a plurality of sequence reads obtained from a sample from a subject; identifying one or more variant sequences based on the sequence read data; providing a variant sequence from the one or more identified variant sequences as input to a trained machine learning model configured to determine a pathogenicity prediction score for the identified variant sequence based on the variant sequence and at least one of additional genomic profiling, demographic pathogenicity prediction score determined for the variant sequence identified in the sample from the subject.

This application belongs to the field of biotechnology and relates to an efficient and specific editing system, method, and application for A-G base substitution. The fusion protein described in this application comprises, from the N-terminus to the C-terminus, a first SaCas9 nickase fragment, a chimeric deaminase fragment, and a second SaCas9 nickase fragment. The deaminase is selected from adenosine deaminase or a variant thereof, specifically ecTadA8e. The amino acid sequence of ecTadA8e is shown in SEQ ID NO. 20, or has more than 80% sequence identity with the amino acid sequence shown in SEQ ID NO. 20, and possesses the function or activity of ecTadA8e. The fusion protein provided in this application, combined with the corresponding guide RNA, can efficiently and specifically replace the base A with G at the target site, providing an effective tool for repairing pathogenic mutations, studying gene function, and improving cell function, and has promising application prospects.

The invention discloses a system for screening Reiye's syndrome based on NOD2 gene new pathogenic mutation. The invention provides a computer device. The computer device comprises a memory, a processor and a computer program stored in the memory, the processor executes the computer program to implement the following steps: receiving NOD2 gene data (cDNA sequence) of a person to be tested; the method comprises the following steps: reacting the NOD2 gene with any one of the following mutations in SEQ ID No.2 stored in a computer: c.380Cgt; t, c, 2657Cgt; t, c.328Ggt; a, c.1295Cgt is selected from the group consisting of the T, c, 1981Ggt; c, and c, 2452Agt; c) performing comparison; and according to a comparison result, outputting information about whether the to-be-detected person is or is suspected to be a patient with the Reiderson's syndrome or about the risk of suffering from the Reiderson's syndrome. The novel pathogenic gene mutation form related to the NOD2 gene of the patient with the Reidersi syndrome is found, the novel pathogenic gene mutation form can serve as a target object to be used for developing a reagent and a computer device for diagnosing or screening the Reidersi syndrome, and the novel pathogenic gene mutation form has important significance on diagnosis and screening of the Reidersi syndrome.

This invention belongs to the field of biopharmaceuticals and relates to a gene therapy drug for hereditary retinal dystrophy related to RLBP1 gene mutations and its application. Specifically, it involves constructing a recombinant AAV-RLBP1 gene therapy drug, which is then injected intravitreally to infect retinal pigment epithelial cells and Müller cells, causing them to express complete and active RLBP1 protein. This invention utilizes a modified AAV vector to package codon-optimized human RLBP1-cDNA, enabling the expression of complete and active RLBP1 protein, which participates in the visual circulation pathway, rescuing retinal dysfunction caused by pathogenic mutations in the RLBP1 gene, improving visual function in patients, or delaying disease progression.

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 discloses a method, device and storage medium for correcting mitochondrial genome sequencing mutations. The mitochondrial genome sequencing mutation correction method of the application comprises the following steps: firstly, retaining possible pathogenic mutations through a known mutation whitelist; and then, removing false positives caused by experimental errors and sequencing errors by using 11 filtering indexes, such as the average value of the position of a read in which the mutation is located, the chain distribution deviation of the mutation and the average base quality value of the mutation, so as to obtain a high-credibility mutation set. The correction method of the application can reduce the workload of mutation interpretation and improve the accuracy of analysis results. Moreover, the correction method of the application is not limited by the number of samples and can be used for correcting single samples or a small number of samples.

The application discloses an ncRNA gene mutation interpretation method, a storage medium and a terminal, and relates to the field of ncRNA gene mutation interpretation.The ncRNA gene mutation interpretation method comprises the following steps: constructing an ncRNA gene pathogenic mutation standard dataset, an ncRNA gene benign variation standard dataset and an ncRNA gene variation harmfulness standard dataset for experimental verification; constructing a scoring model for training ncRNA gene variation harmfulness and an ncRNA gene related disease phenotype similarity scoring model by using the aforementioned datasets; performing logistic regression modeling on harmfulness scoring files and ncRNA gene disease phenotype similarity scoring files containing the same number of pathogenic and benign ncRNA gene variation sites by using data mining software; obtaining an algorithm model for screening and identifying specific evaluation of ncRNA gene pathogenic mutations; training the algorithm model; and interpreting and reporting ncRNA gene mutations by using the trained algorithm model.The ncRNA gene mutation interpretation method can realize standardized, automatic, intelligent and high-throughput clinical interpretation reports for ncRNA gene mutations, greatly improves the interpretation efficiency and the accuracy of the interpretation.

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.

Disclosed herein is a system for discovering a drug active site of protein, to which a drug binds, in a protein containing a pathogenic mutation. The system includes: a pathogenic mutation position de

The invention relates to the technical field of gene editing, in particular to a method for synchronously constructing a mouse model with the point mutation (Knockin, KI) of a Clcn3 gene p.T570I and the knockout (Knockout, KO) of the Clcn3 gene by utilizing a CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) system and application of the mouse model. By optimizing a gRNA targeting site and a donor oligonucleotide sequence, efficient introduction of Clcn3 gene p.T570I point mutation is achieved, and the mutation efficiency is improved by 30% or above compared with a traditional method; the constructed Clcn3 gene p.T570I KI and KO mouse models can be used for stably inheriting target mutation. The method is short in period, low in cost and suitable for large-scale gene editing animal model construction, the first Clcn3 gene p.T570I KI mouse model carrying the human pathogenic mutation site in the world is constructed, and an ideal and reliable genetic tool is provided for deep analysis of the physiological function of the CLCN3 gene and related disease mechanisms.

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 invention discloses application of an MYRF gene mutation detection method in preparation of a conical artery trunk deformity diagnostic reagent, and relates to the technical field of biology, and the technical key point is that the risk of conical artery trunk deformity of a subject is judged by detecting pathogenic mutation of an MYRF gene in a biological sample of the subject. Studies are developed from the aspects of clinical samples, stem cell levels, animal models and the like, the pathogenic mutation of the MYRF gene in the CTA sample is analyzed by utilizing a high-throughput sequencing technology, and the correlation between the gene mutation and disease occurrence is determined; molecular mechanisms of abnormal regulation axes or signal pathways of downstream target genes and heart development related genes caused by MYRF gene defects are analyzed in stem cell and animal models by using modern molecular biology technologies such as ChIP-Seq and RNA-Seq, and an efficient method is provided for diagnosing conic artery trunk deformity.

The application discloses a PTPRQ gene mutation site related to non-syndrome deafness, the mutation site is a novel pathogenic mutation site on a human PTPRQ gene, and is one or more combinations selected from c.4723C>T, c.6040C>T, c.1811T>C, c.5687-6del and c.6560C>T. A specific probe set for detecting a PTPRQ gene mutation, the probe set is a double-stranded DNA probe, is designed according to a PTPRQ gene 45-exon sequence of a transcript NM_001145026 and a flanking region of each 5' end and 3' end of each exon with an extension of 50 bp, contains 169 probes in total, the length of a single probe is 120 bp, a shingled design is adopted, there is an overlapping region between adjacent probes, and the probe density is dynamically adjusted according to the GC content of a target sequence. A detection method of a PTPRQ gene mutation, with peripheral blood or a blood sheet of a to-be-tested person as a sample, extracting genomic DNA, performing targeted capture enrichment by using the specific probe set, combining high-throughput sequencing with standardized bioinformatics analysis, and judging whether the PTPRQ gene mutation exists in the to-be-tested sample.

The present application relates to a SIGMA+ prediction mutation pathogenicity analysis method, system and device. It comprises: obtaining a mutation of a gene to be predicted; mapping the mutation of the gene to be predicted onto a protein structure of the gene to be predicted to obtain a protein structure with the mutation mapped; inputting the protein structure with the mutation mapped into a SIGMA model to obtain a structure feature score of the gene to be predicted; inputting the mutation of the gene to be predicted into a predictor to obtain a variation effect score of the gene to be predicted; and inputting the structure feature score and the variation effect score of the gene to be predicted into a classifier to obtain a classification result of the mutation being a pathogenic mutation or a benign mutation. The method aims to combine SIGMA with other predictors based on the mutation of the gene to be predicted and the protein structure information with the mutation mapped, to explore the high prediction ability and potential application value of SIGMA for mutation pathogenicity.

The application discloses sgRNA targeting GUCY2D mutation and application thereof in preparation of an eye disease treatment drug, and relates to the technical field of biological medicine. A nucleotide sequence of the sgRNA targeting GUCY2D mutation is shown in SEQ ID NO. 1-6 or SEQ ID NO. 8. Based on the screened sgRNA, the sgRNA is loaded into a recombinant AAV expression vector together with a compact adenine base editor, and in-situ precise repair is performed on pathogenic single base mutations in photoreceptor cells through eye local delivery. The application can efficiently correct pathogenic mutations, has no significant off-target risk, can effectively protect the structural integrity of photoreceptor cells, significantly restore the retinal electrophysiological function and overall visual perception ability of a model mouse, and has stable treatment effect, no obvious toxic side effects and good safety.

The invention relates to the technical field of gene detection, and particularly discloses a construction method and application of a spinal muscular atrophy pathogenic mutant gene copy number analysis model. Based on a nanopore sequencing technology, SMN1 and SMN2 copy number variation and intragene mutation can be simultaneously detected through a long and short amplicon combination method. Experimental operation and data analysis are rapid and simple, copy number variation of SMN1 and SMN2 and mutation in SMN1 and SMN2 genes can be accurately detected at the same time, tiny pathogenic mutation can be found easily, and more comprehensive and accurate SMA screening and diagnosis can be carried out. Meanwhile, the long amplicon system disclosed by the invention can be used for detecting g.27134Tgt; the SMN1 '2 + 0' genotype can be detected through detection of a G site, and the problem that comprehensive detection cannot be achieved in the prior art is solved.

The present application relates to a SIGMA-based method, system and device for predicting the pathogenicity of mutations. The method comprises the following steps: obtaining mutations of a gene to be predicted; mapping the mutations of the gene to be predicted onto a protein structure of the gene to be predicted to obtain a protein structure with the mutations mapped; extracting features of the protein structure with the mutations to obtain mutation protein structure features; and inputting the mutation protein structure features into a SIGMA model to obtain a classification result of whether the mutations are pathogenic mutations or benign mutations. The mutation protein structure features include protein level features, residue level features and mutation level features. The method predicts the pathogenicity of mutations based on the SIGMA model and mutation protein structure features, explores the high prediction capability and potential application value of the pathogenicity of mutations, and has a beneficial promoting effect on the analysis and research of the pathogenicity of mutations of gene data.

The invention relates to a preparation method of an APP gene humanized mutation vector and a non-human animal model. The APP gene humanized mutation vector comprises an APP gene knockout vector and an APP gene homologous recombination vector, and the APP gene knockout vector comprises at least one of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 and SEQ ID NO: 4; the APP gene homologous recombinant vector comprises a part of nucleotide sequence for coding non-human animal APP protein, and the non-human animal APP protein contains human APP protein pathogenic mutation sites which are specifically as shown in SEQ ID NO: 5. Humanized mutation is carried out on the non-human animal APP, the original nature of the in-vivo environment of the non-human animal is maintained to the maximum extent, expression and folding of the gene are facilitated, the situation that protein folding is abnormal and conflicts with existing protein of the non-human animal are caused due to direct insertion of the human APP gene is prevented, and the method is closer to the real pathological process; and a more real and reliable disease model in pathology can be obtained.

The application discloses a kind of protein intrinsic disordered region site pathogenic variation calculation identification methods, it is characterized in that, by multi-view heterogeneous feature collaborative modeling mechanism, joint AIUPred energy representation and xTrimoPGLM, ESM etc., the implicit functional characteristics of mutation site are extracted from multiple dimensions;Adaptive feature interaction encoder based on multilayer dynamic hyperconnection structure is constructed, realize high-dimensional heterogeneous features cross-view adaptive gate interaction and reconstruction, effectively inhibit homologous redundancy and noise interference, highlight the key information related to pathogenicity discrimination, finally output pathogenicity prediction score.Experiments show that the method of the present application is significantly better than the existing mainstream mutation effect predictor in the context of protein intrinsic disordered region, especially in the correlation coefficient of Matthews, accuracy and precision, etc. Key indicators are consistently improved.The present application can provide efficient, reliable computing support and intelligent solutions for clinical genetic pathology diagnosis, precision medicine and drug target development.

The present application belongs to the technical field of medical software development, and particularly relates to a highland newborn genetic metabolic disease screening system, a computer readable storage medium and an application thereof. The screening system establishes an altitude stratified multi-level reference value database based on a local healthy newborn cohort, solves the problem of high false positive rate of screening models in plain areas in highland areas by fitting altitude metabolic marker reference median and standard deviation curves. By designing a three-level control data processing flow of "biochemical primary screening-risk score-targeted sequencing automatic triggering", only when the biochemistry is high risk, the population-specific pathogenic mutation library guided targeted sequencing is started, unnecessary whole genome sequencing is avoided, and the screening cost is significantly reduced. The system can also continuously iterate the reference curve and risk threshold according to the confirmed data, realize the closed loop dynamic optimization from sample collection to report generation. The present application has highland adaptability, population specificity and controllable cost, and has good clinical application prospect.

The present application relates to a method for targeting editing RNA based on LEAPER technology, which comprises safely and effectively performing in vivo editing of adenosine to hypoxanthine base on RNA by using LEAPER technology, accurately repairing pathogenic mutation sites, and achieving the purpose of treating all diseases caused by G>A mutations, such as MPS IH.

The present application belongs to the field of animal models, and relates to a kind of RHO-like protein and its application in the construction of retinal pathological animal model.The present application specifically provides a humanized RHO recombinant protein by replacing the amino acid region encoded by the second exon in the Rho protein of mouse with the amino acid region encoded by the second exon in the human RHO protein.Based on the humanized RHO recombinant protein and the humanized RHO recombinant protein with retinal pathogenic mutation, the present application provides a preparation method of humanized mouse model without carrying RHO pathogenic mutation and humanized mouse model carrying RHO pathogenic mutation.The present application provides a preclinical research platform highly simulating human disease for studying the mechanism of RHO pathogenic mutation leading to retinal degeneration and verifying the effectiveness and safety of gene therapy strategy.

The invention relates to multiple fluorescent quantitative PCR (Polymerase Chain Reaction) primers, a probe and a kit for detecting glucose-6-phosphate dehydrogenase deficiency G6PD (Glucose-6-phosphate dehydrogenase) gene variation sites. The invention provides three G6PD gene mutation sites found for the first time, and the three mutation sites are respectively a G6PD gene c.521Ggt, a G6PD gene c.521Ggt and a G6PD gene c.521Ggt. C, c, 661 Tgt, 661 Tgt; c, c, 680Ggt; c variation sites expand the pathogenic variation spectrum of the G6PD gene. The invention further provides a primer, a probe composition and a kit for detecting the G6PD gene variation site of the glucose-6-phosphate dehydrogenase deficiency disease. The primer, the probe composition and the kit are used for screening or diagnosing the glucose-6-phosphate dehydrogenase deficiency disease. The sequences of the primer and the probe are as shown in SEQ ID NO.1-10. The kit disclosed by the invention can comprehensively cover three new pathogenic variation sites of the G6PD gene related to the glucose-6-phosphate dehydrogenase deficiency, is high in accuracy and can specifically detect the pathogenic variation sites.

The application discloses a method and system for predicting phase separation driving residues, which integrates multidimensional sequence information and functional information of proteins, such as word vectors, sequence evolution information, amino acid composition, etc., to construct a machine learning model for predicting phase separation proteins and identifying driving residues. Based on the changes in phase separation prediction probability corresponding to different amino acid sequence changes, the contribution of each amino acid to the phase separation ability of the protein can be quantified. Based on PSPHunter, the phase separation probability of the protein missing each unit is calculated. The lower the score, the greater the impact of the unit on phase separation. The amino acid corresponding to the largest change in phase separation ability after truncation is considered to be a phase separation driving residue, and the region with relatively large influence and forming a valley is considered to be a driving region. The application realizes the prediction of phase separation proteins and the identification of driving residues, and can be further used for quantifying the influence of pathogenic mutations on phase separation and providing an analysis framework for analyzing the relationship between phase separation and diseases.

The present application belongs to the field of gene detection, and particularly relates to a gene combination for screening genetic diseases of newborns, a probe combination, a kit and a preparation method and device thereof. The kit provided in the present application contains capture probes for specific pathogenic genes, high-frequency gene sites and safe drug use gene sites, can detect more than 40,000 pathogenic mutations on 279 genetic disease-related genes at one time, realize rapid and accurate understanding of pathogenic mutation conditions of the subjects, can detect 331 high-frequency gene sites and 74 safe drug use gene sites at one time, provide a unique genetic ID card and drug interpretation, and help the clinic to develop a safer and more effective drug use plan for the subjects. The detection device provided in the present application can automatically analyze and arrange the sequencing data, assist the clinical workers in targeted variation interpretation, improve the work efficiency, and provide necessary conditions for large-scale application of newborn screening.

This invention provides a method for identifying or predicting missense mutations that pose a risk of causing disease. [Solution] A method for predicting whether a missense mutation is pathogenic or benign includes: (1) creating a pathogenic mutation population and a benign mutation population for the target protein; (2) calculating the mutation energy (△△Gmut), standardized solvent-accessible surface area (nSASA), and predicted local distance difference test (pLDDT) score for each individual mutation constituting each population, and calculating the average values ​​of △△Gmut, nSASA, and pLDDT score for each population; (3) calculating △△Gmut, nSASA, and pLDDT score for the missense mutation to be predicted; and (4) calculating the Mahalanobis distance of the missense mutation to be predicted from the pathogenic mutation population and the benign mutation population, respectively.