23 results about "Human sequence" patented technology

The invention discloses an RNA G-quadruplex prediction method and system based on a pre-training model and an RNA secondary structure, and the method comprises the steps: obtaining the position information of human rG4 on a human transcript; for each sequence, filling the same length to two sides according to the position coordinates of the sequence, so that the total length reaches a set length value; obtaining human cDNA sequence data as a reference sequence, and extracting rG4 data containing flanking sequence information from the cDNA sequence according to the filled sequence coordinates as a positive sample sequence; disorganizing each positive sample sequence to obtain a negative sample sequence; rNA secondary structure features of each sample sequence are generated; extracting sequence features of the sample sequence by using a pre-training model; and inputting the sequence features and the RNA secondary structure features into a prediction model for model training. According to the scheme, the secondary structural features of the RNA sequence are utilized, the secondary structural features are introduced as auxiliary information, and the prediction performance of the model can be remarkably improved.

The invention relates to a human source sequence filtering index construction method and device and computer equipment. The method comprises the following steps: acquiring an HG38 human genome and a human genome of at least one human group different from the HG38 human genome, and respectively determining non-redundant target genome sequences, which are not matched with the HG38 human genome, in the human genome of each human group; and constructing a human source sequence filtering index according to the non-redundant target genome sequence. By adopting the method, the filtering index can be constructed on the basis of multiple human genome sequences which are from different sources and are subjected to redundancy elimination processing, so that the sequencing data can be fully filtered out of the human sequences on the basis of the filtering index, the redundant sequences are prevented from being repeatedly analyzed, and the filtering efficiency of the human sequences is improved.

The application provides an anti-Spike protein antibody of a novel coronavirus and an application thereof. By means of genetic engineering and phage surface display library technology, specific antibodies against the S protein of the novel coronavirus are screened from a single-chain antibody library of non-immune full human sequences. The antibodies have an affinity to the S protein of the virus between 1nM and 50nM, the antibodies have an inhibiting effect on the combination of the S protein of the novel coronavirus and human receptor ACE2, and the anti-S protein antibodies of the application have a good ability to combine with the S protein and a potential neutralizing inhibiting effect. The application provides specific antibody candidate molecules for the development of diagnostic reagents, preventive and therapeutic antibody drugs against the novel coronavirus (2019-nCoV) and the treatment of other diseases such as pneumonia caused by the coronavirus.

The application provides an anti-Spike protein antibody of a novel coronavirus and an application thereof. By means of genetic engineering and phage surface display library technology, specific antibodies against the S protein of the novel coronavirus are screened from a single-chain antibody library of non-immune full human sequences. The antibodies have an affinity to the S protein of the virus between 1nM and 50nM, the antibodies have an inhibiting effect on the combination of the S protein of the novel coronavirus and human receptor ACE2, and the anti-S protein antibodies of the application have a good ability to combine with the S protein and a potential neutralizing inhibiting effect. The application provides specific antibody candidate molecules for the development of diagnostic reagents, preventive and therapeutic antibody drugs against the novel coronavirus (2019-nCoV) and the treatment of other diseases such as pneumonia caused by the coronavirus.

Proteases of Group IV (+)ssRNA viruses were found to act on a human sequences in addition to the viral sequences. The identity of the cleavable human sequences is disclosed. Detection of these sequences can act as a diagnostic of infection. It is contemplated that these findings could be employed to facilitate post-translational silencing at the level of protein (e.g., removal of existing proteins), thus serving as a protein analog to CRISPR / Cas9 and RNAi / RISC, and further to enable sequence-specific silencing of host functions without the modification of the host genome.

The present invention provides the use of a PTMA protein coding sequence in the preparation of a drug for treating myocardial infarction. The PTMA protein coding sequence is a mouse PTMA protein coding sequence, a rat PTMA protein coding sequence, or a human PTMA protein coding sequence. The mouse sequence is shown in Seq ID No. 1, the rat sequence is shown in Seq ID No. 2, and the human sequence is shown in Seq ID No. 3. The PTMA protein coding sequence provided by the present invention can promote the proliferation of damaged myocardial cells, regenerate and repair myocardial tissue, reconstruct the heart morphology after myocardial infarction, restore the heart's pumping function, alleviate the development of cardiac pathological remodeling, prevent the occurrence of heart failure, and has a long-term therapeutic effect on cardiac function after myocardial infarction.

The invention relates to the technical field of biological industry, and discloses a single-cell RNA-seq-based HBV expression level and fragment distribution analysis method, which comprises the following steps: constructing position information of each HBV gene in a linear transcriptome and a circular genome to obtain a mapping relationship between the transcriptome and the genome; sequencing original data obtained by scRNAseq is compared to an HBV transcriptome reference sequence, and a human source sequence and an HBV source sequence are recognized; removing a human source sequence to obtain an HBV source transcriptome sequence; converting the position of the HBV source transcriptome sequence aligned on the transcriptome into an alignment position on the genome according to the mapping relation between the transcriptome and the genome; and calculating the number of the sequencing sequences covered on each basic group of the genome, and drawing the coverage depth of each basic group of the HBV genome to obtain the expression level and fragment distribution of the single-cell RNA-seq sequencing data on the HBV genome. The blank of the HBV analysis method based on the single cell resolution is filled.

The invention discloses a blocking agent for eliminating environmental DNA (Deoxyribose Nucleic Acid) of human pollution and a detection method of the environmental DNA, and the blocking agent plays a role in inhibiting amplification of a human source sequence by specifically hybridizing with a human source template and blocking primer annealing or DNA polymerase extension. The invention further provides application of the CRISPR-Cas12a technology to in-vitro removal of human-derived DNA pollution, the method can reduce the sequencing cost and the time cost of bioinformatics processing without affecting detection of target biological groups, and the method is mainly used for treating human pollution in marine environment DNA. And the method can also be used for treating human-derived DNA pollution in similar molecular biology research and application.

The present invention discloses a method and system for predicting RNA G-quadruplex based on a pre-training model and RNA secondary structure, including obtaining the position information of human rG4 on human transcripts; for each sequence, padding the same length to both sides according to its sequence position coordinates so that the total length reaches a set length value; obtaining human cDNA sequence data as a reference sequence, extracting rG4 data containing flanking sequence information from the cDNA sequence according to the filled sequence coordinates as a positive sample sequence; shuffling each positive sample sequence to obtain a negative sample sequence; generating RNA secondary structure features for each sample sequence; extracting sequence features of the sample sequence using a pre-training model; and inputting sequence features and RNA secondary structure features into a prediction model for model training. This scheme utilizes the secondary structure features of RNA sequences and introduces the secondary structure features as auxiliary information, which can significantly improve the prediction performance of the model.

Compositions, kits, and methods are provided for validating patient-specific oligonuclotide assays using spike-in controls. The compositions comprise multiple sets of spike-in oligos, each set including a unique reference sequence and near-neighbor sequences with at least one substitution, insertion, or deletion. Near-neighbor concentrations are less than the reference and collectively span at least four orders of magnitude (e.g., 1:10 to 1:10,000); all sets have the same number of near-neighbors and concentration ratios. Spike-in sequences are unrelated to human sequences and are complementary to synthesis-control oligos at known concentrations. Kits further include synthesis-control oligos and patient-specific oligos for human DNA or RNA targets. Methods involve spiking a sample, co-synthesizing control and patient-specific oligos, assaying by PCR or sequencing, and validating limit of detection and dynamic range by comparing observed counts to known ratios. Applications include ctDNA and cfRNA testing.

The application relates to the technical field of biological industry, and discloses an analysis method for HBV expression level and fragment distribution based on single-cell RNA-seq, constructs position information of each gene of HBV in a linear transcriptome and a circular genome, and obtains a mapping relationship of the transcriptome and the genome; compares original sequencing data obtained by scRNA-seq to an HBV transcriptome reference sequence, identifies human sequences and HBV sequences, removes the human sequences, and obtains HBV source transcriptome sequences; converts the position of the sequencing sequence on the transcriptome into a comparison position on the genome through the mapping relationship of the transcriptome and the genome; calculates the number of sequencing sequences covered on each base of the genome, draws the coverage depth of each base of the HBV genome, and obtains the expression level and fragment distribution of single-cell RNA-seq sequencing data on the HBV genome. The application fills the blank of the HBV analysis method based on single-cell resolution.

The invention discloses a multiple PCR primer design method for drug-resistant mutation targeted detection and application thereof, and belongs to the field of biotechnology primer design, the method comprises the following steps: determining a drug-resistant gene of a target species and a detection site thereof; generating a primer set on the basis of one step length based on the target sequence position of the drug-resistant gene mutation site; the candidate primer is subjected to primer attribute evaluation such as TM value, primer length and GC content; meanwhile, a specific sequence is obtained through human-derived sequence non-specific amplification evaluation, dimer evaluation and comparison of a candidate primer and a nt library, the primer coverage degree is evaluated based on a species genome, a conservative primer sequence is obtained, and finally, a final target drug-resistant gene mutation site primer is obtained based on a mutation frequency result. The method is wide in applicability, parallel detection of multiple drug-resistant genes in a single cell can be achieved, and a new strategy is provided for developing design of multiple PCR system primers for drug-resistant mutation targeted detection.

The invention discloses a construction method and application of an IL22 gene humanized animal, and relates to the technical field of biology. The construction method is characterized in that a whole genome sequence of exons 1-5 of a non-human animal Il22 gene is replaced by a whole genome sequence of exons 1-5 of a human IL22 gene, and a non-human animal genome contains a human sequence shown as SEQ ID NO.4. The construction method comprises the following steps: firstly, constructing a human-derived sequence; an ideal in-vivo research platform is provided for deeply researching a human IL22 signal channel mechanism and screening tumor and immune disease treatment medicines.

The present application relates to a tumor risk prediction method and device based on cfDNA nucleosome fingerprint, belonging to the technical field of in vitro diagnosis. Among them, the method comprises: obtaining whole genome sequencing data of plasma or serum cfDNA; the whole genome sequencing data is subjected to quality control processing to remove non-human sequences to obtain human cfDNA sequencing fragments; the human cfDNA sequencing fragments are aligned to the human reference genome to obtain the genomic coordinates of each fragment and the coverage information thereof on the reference genome; based on the whole genome coverage signal, the enrichment region identification algorithm is used to determine the nucleosome positioning boundary, and the peak signal strength is taken as the nucleosome positioning intensity score; the nucleosome positioning intensity score is input into the tumor risk prediction model which has been trained, and the prediction risk probability of the subject suffering from tumor is output. Greatly improve the accuracy of noninvasive screening tumor prediction tumor risk, and the detection cost is low and the cycle is short.

The present invention discloses a bioinformatics method for pathogenic microorganism metagenomic detection based on second-generation sequencing technology, covering the steps of creating a species list, downloading genome sequences, building a database, quality control of sequencing data, removing human sequences, obtaining a strain identification list A based on k-mer and LCA algorithms, obtaining a strain identification list B based on bwa-mem algorithms, using list B to correct list A, and strain annotation and screening. Compared with the solutions currently on the market, the method provided by the present invention is significantly different. First, in order to ensure the accuracy and comprehensiveness of the analysis results, a human sequence database, a microbial comparison database, and a microbial annotation database were established. In addition, the present invention combines the current mainstream strain identification method based on k-mer and bwa-mem comparisons, realizes the organic combination of the two algorithms, and shows obvious advantages in the identification of low-abundance species. These improvements bring more reliable and more effective solutions to the detection of pathogenic microorganism metagenomics.

The embodiment discloses a computer-assisted method for evaluating and modifying immunogenicity, as well as related computer systems and storage media. The method includes using unsupervised learning of a protein large language model on all human sequences and a supervised deep learning neural networks to establish a predictive scoring model for the humanness score of peptide chains based on the data from the model training dataset to achieve classification between human and non-human species. This involves cutting protein sequences into all possible peptide chains of a preset length using a dynamic window method and importing these chains into the predictive scoring, thereby evaluating their immunogenicity in terms of humanness score. Peptide chains with scores above a certain threshold undergo all possible single-point virtual mutations to generate a set of modified peptide chains which are then reassessed using the model, selecting those with scores above the threshold of humanness for further consideration.

The invention provides a recombinant human collagen type II COLII-23k. The amino acid sequence of the recombinant human collagen type II COLII-23k is as shown in SEQ ID NO. 1. The invention also provides a pichia pastoris engineering bacterium for expressing the collagen COLII-23k, the engineering bacterium comprises a gene for coding the COLII-23k, and the coding gene is connected to a pichia pastoris expression vector in a seamless cloning manner. Meanwhile, the invention also provides an application of the collagen COLII-23k. The invention has the advantages that the active fragment COLII-23k of the human collagen type II provided by the invention is a complete human sequence, does not have redundant amino acid, and has excellent hemostatic activity and skin cell proliferation, adhesion and migration promotion functions; pichia pastoris engineering bacteria for expressing the protein are constructed through seamless cloning, the expression quantity is high, and industrial production is easy; and the collagen is wide in application scene, and can meet the requirements of multiple fields such as hemostasis, wound repair and medical beauty.

The embodiment discloses a computer-assisted method for evaluating and modifying immunogenicity, as well as related computer systems and storage media. The method includes using unsupervised learning of a protein large language model on all human sequences and a supervised deep learning neural networks to establish a predictive scoring model for the humanness score of peptide chains based on the data from the model training dataset to achieve classification between human and non-human species. This involves cutting protein sequences into all possible peptide chains of a preset length using a dynamic window method and importing these chains into the predictive scoring, thereby evaluating their immunogenicity in terms of humanness score. Peptide chains with scores above a certain threshold undergo all possible single-point virtual mutations to generate a set of modified peptide chains which are then reassessed using the model, selecting those with scores above the threshold of humanness for further consideration.

The invention relates to the technical field of biology, in particular to a de novo synthesis method of genome DNA of a super-large-fragment human highly repetitive sequence. The invention provides a strategy for gradually synthesizing and assembling the Mb-level genome DNA fragment with the human highly repetitive sequence from a small fragment, a medium-length fragment, a large fragment to a super-large fragment, the strategy is simple, convenient, efficient and accurate, and the problem of synthesizing the super-large fragment DNA containing the highly repetitive sequence gene in the prior art is solved; accurate assembly of complete chromosomes of saccharomyces cerevisiae is achieved, research on genomes containing complex repetitive sequences is promoted, and the method has wide application prospects in the fields of synthetic biology, gene therapy, biological pharmacy and the like.

The application discloses synthesis of type XVII humanized collagen and a preparation method and application thereof, and particularly relates to the technical field of genetic engineering. The amino acid sequence of the recombinant type XVII collagen is shown as SEQ ID NO. 1. The application retains key functional domains (5 high-hydrophilicity and high-stability peptide segments of 641-685) in the alpha 1 chain of human type XVII collagen, and eliminates non-functional regions. The application adopts 100% human sequence coverage, completely avoids the immunogenicity risk of animal-derived collagen, and has excellent biocompatibility. The functional peptide segments are repeated twice to form a stable structure of 210 amino acids, and the protein functional activity is enhanced. The theoretical isoelectric point (pI=6.07) is close to the pH (7.4) of human tissue fluid, the solubility is excellent, and the applicability is strong.

The invention discloses an anti-platelet GPIb-IX antibody and application thereof, and belongs to the technical field of biological medicine. According to the invention, an initial signal egg GPIb-IX formed by arterial thrombosis is selected as a target spot to prepare the anti-human GPIb-IX humanized antibody. Specifically, human platelets are used as antigens to immunize mice, a mouse anti-human GPIb-IX antibody is obtained through screening and preparation, an adult sequence is mutated to construct the anti-GPIb-IX humanized antibody ATHA, a heavy chain variable region of the antibody comprises VH-CDR3 as shown in SEQ ID NO.1, and a light chain variable region of the antibody comprises VL-CDR3 as shown in SEQ ID NO.2. The Fab segment of the ATHA can effectively inhibit GPIb-IX receptor mediated platelet activation, thrombus formation is inhibited in vivo, meanwhile, the side effects of thrombocytopenia and bleeding are avoided, and the ATHA has the advantages of being high in specificity, good in safety and small in side effect. Meanwhile, ATHA can remove platelets. Therefore, ATHA-Fab has a clinical value of becoming a new antithrombotic drug, and can be used for treating diseases related to arterial thrombosis. ATHA can clear platelets, and can be used for treating platelet number increase diseases or clearing platelets in vivo.

The present invention provides an anti-SARS-CoV-2 Spike protein antibody and its applications. By using genetic engineering and phage display library technology, specific antibodies against the SARS-CoV-2 S protein are screened from a non-immunized single-chain antibody library of fully human sequences. Their affinity for the viral S protein is between 1 nM and 50 nM, and the antibodies inhibit the binding of the SARS-CoV-2 S protein to the human receptor ACE2, indicating that the antiviral S protein antibodies of the present invention have good ability to bind to the S protein and potential neutralizing inhibitory effects. The present invention provides specific antibody candidate molecules for the development of diagnostic reagents, prophylactic and therapeutic antibody drugs against SARS-CoV-2 (2019-nCoV), as well as the treatment of other diseases such as pneumonia caused by coronaviruses.

Polypeptide preparation methods of preparing high-purity ACTH (human sequence) or analogue and large-scale preparation method thereof are described. The main steps include: amino acids are coupled from the C-terminal to the N-terminal by Fmoc solid-phase synthesis method to obtain the crude ACTH (human sequence) or analogue peptidyl-resin with protective groups, wherein the reaction temperature of C-15 peptide synthesis is 40-60° C. After cleavage and precipitation, the crude product of ACTH (human sequence) or analogue is obtained, and then the high-purity product is obtained by liquid chromatography. The chromatographic purity of ACTH (human sequence) or analogue prepared by the invention is more than 99%, the stability is good, and the yield of the target peptide is ≥63%.