A small base editor developed on the basis of the IS200/IS605 transposon family and a use thereof. Provided is a base editing system, comprising: (1) a mutant of an ISDra2-TnpB protein and/or a nucleic acid encoding the mutant of the ISDra2-TnpB protein; (2) a deaminase and/or a nucleic acid encoding the deaminase; and (3) a guide RNA and/or a nucleic acid encoding the guide RNA, wherein the mutant of the ISDra2-TnpB protein has a genome targeting function but does not have a DNA cleavage function.
A method for labeling APC and T cells on the basis of LIP3000 liposome transfection. A method for labeling a variety of cells, which comprises delivering tag sequences for different cells into corresponding cells, thereby achieving the labeling of the variety of cells.
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
3.
METHOD FOR PREPARING AMPHIPHILIC POLYMER AND USE THEREOF
The present disclosure relates to the technical field of polymer materials, and in particular, the present disclosure relates to a method for preparing an amphiphilic polymer and a use thereof. The preparation method uses a hydrophobic polymer having good molecular chain flexibility as a hydrophobic chain to connect a hydrophilic amphoteric monomer molecule to at least one end of the hydrophobic polymer, so as to obtain an amphiphilic polymer with controllable molecular weight distribution of the polymer. The present disclosure uses a hydrophobic polymer having good molecular chain flexibility as a hydrophobic chain to improve membrane stability and reduce amphiphilic polymer molecular weight distribution to a certain extent, which increases interaction between amphiphilic polymers and membrane proteins, improves membrane protein stability in polymer biomimetic membranes, and lays a firmer foundation for the construction of biomimetic cell membranes.
C08F 293/00 - Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule
C08F 8/30 - Introducing nitrogen atoms or nitrogen-containing groups
C08G 77/392 - Polysiloxanes modified by chemical after-treatment containing atoms other than carbon, hydrogen, oxygen or silicon containing sulfur
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
An antibody or an antigen-binding fragment thereof, comprising a CDR selected from at least one of the following: a heavy chain variable region CDR having an amino acid sequence as shown in any one of SEQ ID NOs: 1-3 and 7-9, or a conservatively modified amino acid sequence thereof; or a light chain variable region CDR having an amino acid sequence as shown in any one of SEQ ID NOs: 4-6 and 10-12, or a conservatively modified amino acid sequence thereof.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
5.
METHOD AND SYSTEM FOR PREDICTING RANGE OF HOSTS TARGETED BY PHAGES, AND CORRESPONDING COMPUTER DEVICE OR MEDIUM
Provided in the present invention are a method and system for predicting hosts targeted by phages. In the method, host prediction can be performed simply by using tail proteins of phages, thus solving the problem of whole-genome feature redundancy, and moreover, efficient learning is achieved by using both physicochemical properties and contextual information features of tail proteins, such that the prediction accuracy at the family, genus and species levels is higher than that of other machine learning models (with an average improvement of 30%). Thus, the present invention overcomes the technical challenge of achieving both high recall and high precision, greatly expands the prediction range (categories), and solves major technical problems of current prediction tools, thus having broad application prospects in the field of prediction of hosts targeted by phages.
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
6.
METHOD FOR PREPARING POLYPEPTIDE ARRAY AND USE OF POLYPEPTIDE ARRAY IN DETECTION OF BIOMOLECULAR INTERACTION
A method for preparing a polypeptide array, which method comprises: providing one or more DNA molecules; placing the DNA molecules on a solid-phase carrier, wherein a capture probe is immobilized on the solid-phase carrier; performing a transcription reaction with the DNA molecules as templates to obtain corresponding RNA molecules, wherein the RNA molecules are captured by the capture probe; digesting the DNA molecules, thereby obtaining an RNA array, wherein the RNA array contains a capture probe and the RNA molecules captured by the capture probe; and performing in-vitro translation with the RNA molecules as templates to obtain corresponding polypeptides, thereby obtaining the polypeptide array, wherein the polypeptide array contains the capture probe and the polypeptides captured by the capture probe.
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C12N 15/67 - General methods for enhancing the expression
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
Provided is an isolated Cas protein or a variant or homolog thereof. The Cas protein is one or more selected from the group consisting of the following: C2C9-f3 having the amino acid sequence as shown in SEQ ID NO: 1, C2C9-f4 having the amino acid sequence as shown in SEQ ID NO: 2, C2C9-f10 having the amino acid sequence as shown in SEQ ID NO: 3, and C2C9-f11 comprising the amino acid sequence as shown in SEQ ID NO: 4.
The present invention provides a differential modification method and use for a polypeptide. The differential modification method for a polypeptide comprises: step S1. providing an aromatic aldehyde and a polypeptide, and mixing the aromatic aldehyde and the polypeptide in a reaction solvent, so that an aldehyde group of the aromatic aldehyde reacts with an N-terminus of the polypeptide to generate a dihydroimidazolone intermediate reaction solution; and step S2. adding an alkaline substance and fluorosulfonyl azide to the dihydroimidazolone intermediate reaction solution for an azide reaction to obtain a modified polypeptide reaction solution. By means of the reactivity difference of polypeptide terminal groups, the present application achieves differential modifications of the N-terminus and C-terminus of the polypeptide separately by means of a one-pot two-step method in a similar pH environment, especially the modification of amino groups at two termini of a polypeptide having lysine at the C-terminus with different groups separately. The specificity is improved, the reaction conditions are simple and mild, the route is short, the operation is convenient, large-scale production is easily implemented, and the cost is saved.
Proposed is a use of a polypeptide fragment as a barcode in nucleic acid sequencing. According to embodiments, the barcode comprises a sample barcode or a molecular barcode. According to the embodiments, in the nucleic acid sequencing, a sequencing library comprises a single strand of a nucleic acid to be sequenced, the polypeptide fragment, and a single strand of a sequencing adapter nucleic acid. In nucleic acid sequencing, the introduction of the polypeptide fragment significantly enhances the characteristics of a sequencing signal and improves the accuracy of sample differentiation.
A method for preparing a nucleic acid-polypeptide complex. The method comprises: providing a polypeptide fragment to be tested and oligonucleotide fragments, wherein the oligonucleotide fragments include a first oligonucleotide fragment and a second oligonucleotide fragment, the 3'-end of the first oligonucleotide fragment is provided with a first modification group, and the 5'-end of the second oligonucleotide fragment is provided with a second modification group; and directionally linking said polypeptide fragment to the first oligonucleotide fragment and the second oligonucleotide fragment to obtain a nucleic acid-polypeptide complex, wherein the N-terminus of said polypeptide fragment is provided with a modification group N, the C-terminus of said polypeptide fragment is provided with a modification group C, the modification group N at the N-terminus of said polypeptide fragment is adapted to be linked to the first modification group at the 3'-end of the first oligonucleotide fragment, and the modification group C at the C-terminus of said polypeptide fragment is adapted to be linked to the second modification group at the 5'-end of the second oligonucleotide fragment.
Provided are a reverse transcriptase or a biologically active fragment thereof and the use thereof. The reverse transcriptase or the biologically active fragment thereof has: a. an amino acid sequence as shown in any one of SEQ ID NOs: 1-3; b. an amino acid sequence having one or more amino acid substitutions, deletions and/or additions on the basis of the amino acid sequence as shown in any one of SEQ ID NOs: 1-3; or c. an amino acid sequence having at least 70% identity to the amino acid sequence as shown in any one of SEQ ID NOs: 1-3. Moreover, the reverse transcriptase or the biologically active fragment thereof has a reverse transcriptase function.
Provided are a transposase or a biologically active fragment thereof and a use thereof, the transposase or the biologically active fragment thereof: a. comprising an amino acid sequence shown in any one of SEQ ID NOs:1-2; b. comprising an amino acid sequence having one or more amino acid substitutions, deletions, and/or additions as compared to the amino acid sequence shown in any one of SEQ ID NOs:1-2; or c. comprising an amino acid sequence having at least 70% identity to the amino acid sequence shown in any one of SEQ ID NOs:1-2, wherein the transposase or the biologically active fragment thereof has transposase functions.
The present invention provides a novel DNA ligase, comprising: an amino acid sequence as shown in SEQ ID NO: 2 or SEQ ID NO: 4; or, compared with the amino acid sequence as shown in SEQ ID NO: 2 or SEQ ID NO: 4, an amino acid sequence obtained after substitution and/or deletion and/or addition of one or more amino acid residues and retaining DNA ligation activity; or an amino acid sequence having at least 70% identity with the amino acid sequence as shown in SEQ ID NO: 2 or SEQ ID NO: 4 and retaining DNA ligation activity. The novel DNA ligase of the present invention has good ligation activity, and can be applied to a variety of scenarios.
Provided are a terminal deoxynucleotidyl transferase (TdT) or a biologically active fragment thereof and the use thereof. The terminal deoxynucleotidyl transferase or the biologically active fragment thereof comprises a catalytic domain, the catalytic domain comprising: a. an amino acid sequence shown as SEQ ID NO: 1 or 2; b. an amino acid sequence having one or more amino acid substitutions, deletions and/or additions as compared to the amino acid sequence shown as SEQ ID NO: 1 or 2; or c. an amino acid sequence having at least 60% identity as compared to the amino acid sequence shown as SEQ ID NO: 1 or 2. The catalytic domain has the function of catalyzing a single nucleotide to be polymerized on the 3'-OH end of a polynucleotide chain.
The present application relates to a method for optimizing a nucleic acid library, and more specifically relates to a method for optimizing a single-cell library or spatio-temporal omics library. The nucleic acid library comprises a valid sequence and an invalid sequence. The valid sequence sequentially comprises a barcode domain, a target nucleic acid domain and a first universal primer binding domain. The invalid sequence comprises a first invalid sequence, wherein the first invalid sequence contains a barcode domain but does not contain a target nucleic acid domain or a first universal primer binding domain. The method comprises removing a first invalid sequence, and removing the first invalid sequence comprises the following steps: removing the first invalid sequence by using a first primer, wherein the first primer is partially or completely complementary to the first universal primer binding domain, and the first primer is labeled with a first distinguishing element.
The present invention pertains to the field of biotechnology. Disclosed is a method for identifying 5-methylcytosine (5mC) in a target nucleic acid. The method involves mild-reaction DNA methylation analysis, can quantitatively detect modified cytosines at a base resolution without affecting unmodified cytosines, and is implemented by combining TET enzyme oxidation and sulfinic acid derivative reduction. The sulfinic acid derivative reducing agent used has stable chemical properties, is safer, and can also better reduce damage to DNA samples.
Provided are a method for constructing a disease risk alert model, a method and apparatus for alerting to a disease risk, and an electronic device, a computer-readable storage medium, a computer program product and a computer program. The method comprises: acquiring a first input feature on the basis of genomic data of cell-free DNA in a sample; on the basis of a disease phenotype of the sample, acquiring a second input feature; and on the basis of the first input feature and the second input feature, constructing a disease risk alert model, wherein the genomic data comprises a fragment length of the cell-free DNA, sequence information of the cell-free DNA and position information of the cell-free DNA aligned to a reference genome.
G16B 25/10 - Gene or protein expression profilingExpression-ratio estimation or normalisation
G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
G16H 50/30 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indicesICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for individual health risk assessment
CITY UNIVERSITY OF HONG KONG SHENZHEN RESEARCH INSTITUTE (China)
BGI-SHENZHEN (China)
Inventor
Gong, Jinhua
Wang, Meiniang
Deng, Xin
Abstract
Relate to an isolated vNAR single domain antibody that specifically binds to SARS-CoV-2 nucleocapsid protein, and a process for preparing the same.This isolated vNAR single domain antibody are also included.
Provided are an anti-human CD117 nanobody and use thereof. The nanobody comprises at least one VHH chain. The VHH chain comprises a CDR1, a CDR2, and a CDR3. The amino acid sequence of the CDR1 is set forth in SEQ ID NO: 4, the amino acid sequence of the CDR2 is set forth in SEQ ID NO: 5, and the amino acid sequence of the CDR3 is set forth in SEQ ID NO: 6; or the amino acid sequence of the CDR1 is set forth in SEQ ID NO: 7, the amino acid sequence of the CDR2 is set forth in SEQ ID NO: 8, and the amino acid sequence of the CDR3 is set forth in SEQ ID NO: 9; or the amino acid sequence of the CDR1 is set forth in SEQ ID NO: 10, the amino acid sequence of the CDR2 is set forth in SEQ ID NO: 11, and the amino acid sequence of the CDR3 is set forth in SEQ ID NO: 12. The use is use of the nanobody and a formulation thereof in the preparation of a drug for treating thalassemia. The nanobody has a good binding ability to CD117, and has the advantages of small molecular weight, high binding activity, low immunogenicity, easy modification, etc.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Provided is a nucleic acid-polypeptide complex which comprises a single-stranded nucleic acid and a polypeptide fragment, wherein both ends of the polypeptide fragment are covalently linked to both ends of the single-stranded nucleic acid, respectively. The nucleic acid-polypeptide complex has a high coupling efficiency, a high yield, and a simple preparation method.
A method for constructing a nucleic acid library, a method for nanopore sequencing and the use thereof. The construction method comprises: a) providing a circular library, wherein the circular library comprises a circular nucleic acid molecule, and the circular nucleic acid molecule comprises a nucleic acid sequence to be tested and a first hairpin sequence capable of forming a first hairpin structure; b) performing rolling circle amplification on the circular nucleic acid molecule to generate at least one copy to obtain a rolling circle amplification strand; c) cleaving a single strand of a stem structure in a second hairpin structure on the rolling circle amplification strand to obtain an amplified copy sequence; and d) performing (i) extension or (ii) extension followed by ligation on the amplified copy sequence by means of using a single-stranded overhang sequence of the amplified copy sequence as a template, so as to obtain a polynucleotide having a stem-loop structure, that is, obtaining a nucleic acid library comprising polynucleotides having a stem-loop structure. The present invention can solve the problem in the prior art of it being difficult to achieve copy number amplification while constructing a double-stranded nucleic acid library, and is applicable to the field of nucleic acid library construction.
The present invention provides a nanopore protein complex and a use thereof. The nanopore protein complex comprises: a nanopore protein and multiple auxiliary proteins, the nanopore protein comprising multiple porin monomers and a nanopore channel structure formed by polymerization of the porin monomers, each auxiliary protein having an N-terminus thereof located within the nanopore channel structure, and the multiple auxiliary proteins being connected one-to-one with the multiple porin monomers and, together with the nanopore channel structure forming a continuous channel; along a direction in which an analyte passes through the continuous channel, the continuous channel comprises a first constriction region and a second constriction region that are connected in sequence, the first constriction region being formed at least in part by the nanopore protein, the second constriction region being formed in part or in whole by the auxiliary proteins, and the nanopore protein being wild-type or a mutant.
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
C12N 15/70 - Vectors or expression systems specially adapted for E. coli
C12N 1/21 - BacteriaCulture media therefor modified by introduction of foreign genetic material
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 27/26 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variablesInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by using electrolysis or electrophoresis
C12M 1/34 - Measuring or testing with condition measuring or sensing means, e.g. colony counters
C12M 1/00 - Apparatus for enzymology or microbiology
A cell annotation method and apparatus, an electronic device, and a computer program product. The method comprises: inputting a gene expression matrix of a target cell into a hierarchical cell annotation model, and extracting M levels of cell features; and on the basis of the cell features, outputting an annotation result of the target cell in a hierarchical cell classification system, wherein the cell features comprise global features and local features, the global features are used for determining the level to which the cell belongs and a global cell type, and the local features are used for determining local cell classification of each level.
A support carrier, a carrier assembly, and a biochemical substance analysis system. The support carrier comprises a base, a cover, and an elastic pad. The base is configured to support a slide, and at least one effective area is provided on the slide. The cover is configured to be detachably rotatably connected to the base, so that the cover can be opened and closed relative to the base. The cover is provided with at least one cover opening, and the cover opening is configured to at least partially overlap the effective area in the thickness direction of the support carrier when the cover is closed relative to the base. The elastic pad is provided with at least one cavity opening. The elastic pad is configured to elastically abut between the cover and the slide when the cover is closed relative to the base, so that the cavity opening at least partially overlaps the cover opening in the thickness direction, and one side of the cavity opening is sealed by the slide to form a reaction cavity.
Provided is a method for constructing a nucleic acid library. The method comprises: (a) providing a nucleic acid molecule comprising a self-amplifying adapter, the self-amplifying adapter having a palindromic sequence; (b) performing self-amplification on the nucleic acid molecule to obtain the nucleic acid library, wherein the self-amplification is realized by means of one or more cycles of a heating treatment and a cooling treatment, the palindromic sequence of the self-amplifying adapter is adapted for forming a hairpin structure, and the hairpin structure is adapted for serving as a primer for self-amplification.
Provided are a binary complex containing a chaperone molecule and the use thereof in polypeptide sequencing. The binary complex comprises a chaperone molecule and a polypeptide to be detected that are covalently linked, wherein the chaperone molecule is selected from any one or more of the following: PEG, a spacer, a deoxyribose phosphate, a ribose phosphate, a nucleotide, a deoxynucleotide, a peptide nucleic acid or a locked nucleotide; the number of constituent units of the chaperone molecule is ≥1; and the number of amino acids of said polypeptide is ≥2. The above development and use are conducive to improving the resolution of nanopore polypeptide sequencing, and are of great significance for the advancement of nanopore polypeptide sequencing technology.
Provided are a method and kit for constructing a multi-copy nucleic acid library. The construction method comprises: performing droplet-based isothermal amplification on target nucleic acids to obtain amplified products; ligating the amplified products to obtain multi-copy target nucleic acids; and disrupting the droplets and constructing the released multi-copy target nucleic acids into a multi-copy nucleic acid library. The method improves the construction efficiency of sequencing libraries, and single-molecule sequencing is performed using the multi-copy nucleic acid library that is obtained by the method, thereby improving the sequencing accuracy.
Provided are a tissue tracing method for cell-free DNA, a tissue lesion risk notification method, a cell-free DNA-based cancer risk indication method, a cell-free DNA-based gestational disease risk indication method, a cell-free DNA-based receptor tolerance risk notification method, a disease treatment effect evaluation or prognosis method and apparatus, an electronic device, a computer-readable storage medium, a computer program product and a computer program. The tissue tracing method for cell-free DNA comprises: acquiring a tissue-specific expression gene set of a tissue; acquiring first distribution information of cell-free DNA derived from a sample on specific regions of genes in the tissue-specific expression gene set; and, on the basis of the first distribution information, acquiring a tissue contribution index of the tissue in the cell-free DNA, so as to trace the tissue of the cell-free DNA, wherein the specific regions comprise transcription start site (TSS) regions.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
29.
METHOD AND APPARATUS FOR PROCESSING POLYPEPTIDE NANOPORE SEQUENCING SIGNAL
The present invention relates to the technical field of biological sequencing or other related technical fields. Disclosed are a method and apparatus for processing a polypeptide nanopore sequencing signal. The method comprises: upon receiving N polypeptide sequencing signals, acquiring a distance score between each polypeptide sequencing signal and a reference density matrix model; and on the basis of the distance scores, screening the N polypeptide sequencing signals for a target polypeptide sequencing signal. The reference density matrix model contains a frequency-density reference matrix generated after signal filtering of known sequencing samples. The present invention solves the technical problem in the related art that unknown high-throughput polypeptide nanopore sequencing signals cannot be effectively screened, resulting in a large amount of interference data and low data quality.
Provided are a polypeptide sequencing data screening method, a neural network model training method, and a related device, relating to the technical field of biotechnology. The polypeptide sequencing data screening method comprises: acquiring a plurality of pieces of original polypeptide sequencing data, wherein the original polypeptide sequencing data is obtained by means of nanopore sequencing technology; performing feature extraction on the plurality of pieces of original polypeptide sequencing data on the basis of a preset neural network model, to obtain a plurality of depth features, wherein the neural network model is a model obtained by training on the basis of preset sample data, and the preset sample data comprises a plurality of pieces of sample polypeptide sequencing data and classification labels corresponding thereto; performing point cloud density estimation on the plurality of depth features, to obtain a point cloud density estimation value corresponding to each depth feature; and performing screening on the original polypeptide sequencing data on the basis of the point cloud density estimation value, to obtain a screening result. Provided embodiments can reduce noise data of a polypeptide sequence and improve the quality of the polypeptide sequence.
The present invention relates to the field of sequencing. Specifically provided are a method for regulating the activity of a biomolecule, and a corresponding device or system. Further provided are methods for identifying or characterizing the biomolecule. The methods are suitable for detection and/or sequencing, in particular, nanopore sequencing.
A detection apparatus, comprising a housing assembly, and a loading module, temperature control modules, and a main control module that are located in the housing assembly. The loading module is provided with a mounting position, and the loading module is configured for detachably mounting a detection module in the mounting position. The loading module is also configured for electrically connecting to the detection module. The temperature control modules are stacked below the loading module. The temperature control modules are configured for bearing the detection module located at the loading module and regulating the temperature of the detection module. The main control module is configured for controlling the temperature control modules and the detection module located on the loading module to operate cooperatively. The detection apparatus integrates the loading module and the temperature control modules, resulting in a simple structure. The detection module is convenient to load and can enable good electrical signal transmission and temperature conduction, improving the detection efficiency.
Provided are a base calling method, a base calling model training method, and an electronic device. The base calling method comprises: performing first pre-processing on signal data, and obtaining first pre-processed data; inputting the first pre-processed data into a pre-trained base calling model, and obtaining a data feature of the first pre-processed data; and using a decoder to decode the data feature, and obtaining a base sequence corresponding to the signal data. The base calling model training method comprises: performing second pre-processing on sample data, and obtaining second pre-processed sample data; and training a preset model on the basis of the second pre-processed sample data, and obtaining a base calling model that meets a preset requirement. By using the described method, the precision of prediction by a base calling model can be improved, thereby improving the accuracy of base calling.
Provided is a recombinant KOD polymerase. The recombinant KOD polymerase has a sequence having at least 85% identity with the sequence of a wild-type KOD polymerase, wherein the recombinant KOD polymerase contains one or more mutations at one or more of the following positions corresponding to the sequence of the wild-type KOD polymerase: positions 141, 143, 408, 409, 410, and 485. The recombinant KOD polymerase has DNA polymerase activity, wherein the sequence of the wild-type KOD polymerase is as shown in SEQ ID NO: 1.
Provided are a method for purifying a molecule-to-be-sequenced-duplex complex, a method for sequencing a purified nucleic acid-polypeptide complex obtained on the basis of the method, and a kit. The method comprises: step a. providing a mixture comprising a ligation product, wherein the ligation product comprises a molecule to be sequenced and a duplex, the duplex comprises a template molecule, a first nucleic acid, and a second nucleic acid, at least a portion of the first nucleic acid is complementarily paired with a first segment of the template molecule, at least a portion of the second nucleic acid is complementarily paired with a second segment of the template molecule, and the template molecule has a first site; step b. from the mixture by means of at least one of a carrier and a carrier complex, capturing the ligation product and an optional duplex to which no molecule to be sequenced is ligated, wherein the carrier complex comprises a third nucleic acid and the carrier; step c. using a first reagent to cleave at a first site in both the ligation product and the optional duplex to which no molecule to be sequenced is ligated, to obtain a first purified product; and step d. using a second reagent to cleave at a second site in the first purified product to obtain a second purified product, wherein at least one of the third nucleic acid, the second nucleic acid, and the second segment of the template molecule has the second site.
Provided is a new porin suitable for nanopore detection. The porin is formed by means of the polymerization of porin monomers, and the porin monomers contain a barrel domain, which barrel domain has: a. an amino acid sequence as shown in SEQ ID NO: 1; b. an amino acid sequence in which, compared to the amino acid sequence as shown in SEQ ID NO: 1, one or more amino acids are substituted, deleted, and/or added, wherein the barrel segment has the function of forming a pore channel structure upon polymerization; or c. an amino acid sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to the amino acid sequence as shown in SEQ ID NO: 1, wherein the barrel segment the function of forming a pore channel structure upon polymerization.
C07K 14/35 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Mycobacteriaceae (F)
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 27/26 - Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variablesInvestigating or analysing materials by the use of electric, electrochemical, or magnetic means by using electrolysis or electrophoresis
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
A61K 47/42 - ProteinsPolypeptidesDegradation products thereofDerivatives thereof, e.g. albumin, gelatin or zein
Provided is a recombinant B7 polymerase. The recombinant B7 polymerase has a sequence having at least 85% identity to the sequence of a wild-type B7 polymerase. The recombinant B7 polymerase comprises mutations corresponding to one or more positions of the sequence of the wild-type B7 polymerase, selected from the following: positions 169, 171, 441, 442, and 443. The recombinant B7 polymerase has DNA polymerase activity. The sequence of the wild B7 polymerase is as shown in SEQ ID NO: 1.
Provided are a nanopore protein complex, a construction method therefor, and a use thereof. The nanopore complex comprises: a nanopore protein and an accessory protein. The nanopore protein comprises a nanopore cavity, and the nanopore cavity is formed by polymerizing a plurality of pore protein monomers. The accessory protein is formed by polymerizing a plurality of accessory protein monomers. The N-terminus of the accessory protein is embedded in the nanopore cavity and forms a continuous channel together with the nanopore cavity. On the basis of the moving direction of an analyte passing through the continuous channel, the continuous channel comprises a first sensing region and a second sensing region which are communicated sequentially, wherein the first sensing region is formed by part of the nanopore protein, and the second sensing region is formed by part or all of the accessory protein. A nanopore protein monomer is selected from a protein having an amino acid sequence as shown in SEQ ID NO: 1 and a variant thereof, and an accessory protein monomer is selected from a protein having an amino acid sequence as shown in SEQ ID NO: 3 and a variant thereof.
Provided is a sequencing buffer solution and a method for the nanopore-based capture of a target nucleic acid sequence. The sequencing buffer solution comprises a molecular crowding agent. The method employs a nanopore to capture a target nucleic acid sequence from a sequencing buffer solution. The sequencing buffer solution and the method increase the probability that a sequencing library (or other target analyte) is captured by the nanopore protein during the sequencing process, thereby increasing sequencing data output.
Provided are a barcode marking method and a barcode. The method comprises: introducing at least one special nucleotide into a barcode to be marked, to obtain a marked barcode. The barcode comprises the at least one special nucleotide. According to the method of the embodiments, the marked barcode can generate a special current signal when passing through a nanopore. According to the barcode of the embodiments, the special current signal can be generated when the barcode passes through a nanopore.
C12Q 1/66 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving luciferase
C07D 233/54 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
C07D 403/02 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings
C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
Provided is a DNA polymerase. The DNA polymerase contains (i) an amino acid sequence as shown in SEQ ID NO: 1; or (ii) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to the amino acid sequence as shown in SEQ ID NO: 1 and having polymerase activity; or (iii) an amino acid sequence differing from the amino acid sequence as shown in SEQ ID NO: 1 by no more than 20, 15, 10, 5, 4, 3, 2, or 1 amino acids and having polymerase activity.
Provided are a sequencing library construction method, a nucleic acid sequencing method, a nanopore sequencing method and a use. The sequencing library construction method comprises: using a first primer to carry out rolling circle amplification on a target nucleic acid cyclic library; using a second primer to carry out first nucleic acid amplification on a free fragment generated by rolling circle amplification; linearizing the target nucleic acid cyclic library to terminate rolling circle amplification, generating an extensible 3' end as an amplification primer after linearizing the target nucleic acid cyclic library, and at the same time, using the second primer to carry out second nucleic acid amplification on the free fragment generated by rolling circle amplification, to obtain a double-stranded amplification product; and linking a sequencing adapter to the double-stranded amplification product to prepare a sequencing library. The present invention can solve the problem in the prior art of low accuracy in nanopore sequencing, and is suitable for the field of high-throughput sequencing.
The present invention relates to the field of tissue-derived cell identification, in particular to a method for identifying tissue-derived cells in the body fluid based on single-cell sequencing technology. In the present invention, on the basis of high-throughput single-cell RNA sequencing data of cell samples obtained from body fluids, by means of reference component analysis (RCA), expression of known tissue-related marker genes, and a tissue-derived cell prediction model constructed based on logistic regression, the specific identification of tissue-derived cells in body fluids is achieved.
The present application relates to a level detection method and apparatus for a time series signal, a computer device, a storage medium, and a computer program product. The method comprises: obtaining a time series signal; dividing the time series signal into a preset number of intervals, counting the number of points in each interval, and constructing a histogram on the basis of the number of points in each interval; obtaining peak data in the histogram; obtaining a median and a standard deviation of time series data corresponding to each peak in the peak data; and determining a level detection result for the time series signal on the basis of the median and the standard deviation.
Provided are a DNA polymerase and a use thereof. The DNA polymerase comprises: (a) a protein containing an amino acid sequence as shown in SEQ ID NO: 1; (b) a protein having DNA polymerase activity, wherein substitution, deletion, and/or addition of one or more amino occurs at at least one site in an exonuclease active sequence region and/or motif A of the amino acid sequence as shown in in SEQ ID NO: 1; or (c) a protein having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% or more homology to the protein in (a) or (b) and having DNA polymerase activity. The present invention can solve the problem of few DNA polymerase types in the prior art and is applicable to the field of DNA polymerases.
Provided are a gene prediction method and apparatus, a computer device, and a computer readable storage medium. The method comprises: acquiring a template gene sequence, and a genetic gene sequence and a free gene sequence which correspond to a subject under test (step S102); determining a target gene site in the genetic gene sequence and the free gene sequence (step S104); extracting feature data corresponding to the target gene site, wherein the feature data is used for representing attribute features of the target gene site, and the feature data comprises first input data and second input data (step S106); acquiring a target gene prediction model, wherein the target gene prediction model comprises a first network, a second network, and a third network, and an output of the first network and the second network is an input of the third network (step S108); and respectively inputting the first input data and the second input data into the first network and the second network to obtain a gene prediction result outputted by the third network and corresponding to said subject (step S110).
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
49.
METHOD FOR SYNTHESIZING DOUBLE-STRANDED CDNA AND USE THEREOF
Provided are a method for synthesizing double-stranded cDNA and the use thereof. The method comprises: performing a reverse transcription reaction on an mRNA template by means of using a reverse transcription primer and a reverse transcription mixture, so as to obtain double-stranded cDNA, wherein the reverse transcription mixture comprises a reverse transcriptase having a template switching function, a template switch oligo and dNTPs; in the reverse transcription mixture, the final concentration of the reverse transcriptase is 5-20 U/μL, the final concentration of the template switch oligo is 2-12.5 μM, and the final concentration of dNTPs is 1-10 mM. The reverse transcription reaction is performed by means of using the reverse transcription mixture. By means of optimizing the amounts of the dNTPs, the template switch oligo and the reverse transcriptase involved in the reaction in the reverse transcription reaction system, the efficiency of the reverse transcription reaction is improved, enabling the production of a double-stranded cDNA product in a one-step reaction, thereby greatly shortening the reverse transcription reaction time and thus improving the quality of the double-stranded cDNA product.
The present invention relates to the field of nucleic acid editing, and in particular to the technical field of clustered regularly interspaced short palindromic repeats (CRISPR). Specifically, the present invention relates to a system or composition comprising a Cas effector protein, and a vector system, a delivery composition, and a kit comprising the system or composition. The present invention further relates to a use of the system or composition, the vector system, the delivery composition, and the kit in nucleic acid editing, and methods for nucleic acid editing, nucleic acid detection, and disease treatment.
A microfluidic device and a microfluidic sensing system. The microfluidic device (100) comprises a microfluidic body (10) and a flow channel switching assembly (20). The microfluidic body (10) is provided with a first main flow channel (11), a second main flow channel (12), a first waste liquid flow channel (13), and a second waste liquid flow channel (14). The flow channel switching assembly (20) is rotatably connected to the microfluidic body (10). The flow channel switching assembly (20) is used for rotating to a first position so as to enable the first main flow channel (11) to be communicated with the second main flow channel (12). The flow channel switching assembly (20) is further used for rotating to a second position so as to enable the first main flow channel (11), the second main flow channel (12), and the first waste liquid flow channel (13) to be communicated. When the flow channel switching assembly (20) is located at the second position, the second main flow channel (12) and the second waste liquid flow channel (14) are isolated from each other.
Provided is a method for constructing an mtscCAT-seq sequencing library on the basis of droplet microfluidics, the method comprising: fixing and permeabilizing a cell by using a fixative and a lysing agent, respectively; use a transposase to treat the cell which has been subjected to fixation and permeabilization, which transposase is embedded with a first specific tag sequence, so as to obtain gDNA and mtDNA which are linked to the first specific tag sequence, the gDNA being derived from an open chromatin region; treating the cell by using a transcriptome capture sequence, which transcriptome capture sequence comprises a second specific tag sequence, so as to obtain, by means of reverse transcription, cDNA linked to the second specific tag sequence; generating a droplet on the basis of droplet microfluidics so as to encapsulate the cell and a first microbead within the droplet, wherein the gDNA, the mtDNA and the cDNA are captured by the first microbead; and obtaining a sequencing library for mtscCAT-seq on the basis of the captured gDNA, mtDNA and cDNA.
Provided is a method for constructing a spatial proteomics sequencing library from paraffin-embedded tissue sections. The method comprises: providing a solid-phase carrier and an antibody-nucleic acid conjugate; attaching a paraffin-embedded tissue section sample to the solid-phase carrier and carrying out baking, dewaxing, hydration, de-crosslinking, and blocking treatments to obtain a blocked solid-phase carrier; incubating the antibody-nucleic acid conjugate and the blocked solid-phase carrier to obtain a protein-captured solid-phase carrier; carrying out a permeabilization treatment and DNA synthesis on the protein-captured solid-phase carrier to obtain cDNA; and releasing the cDNA from the solid-phase carrier, collecting the cDNA, and amplifying the cDNA to obtain a sequencing library.
A manufacturing method for a chip electrode structure, comprising the following steps: providing a layered structure, comprising a first conductive layer, a first transition layer, and a second conductive layer that are successively stacked, wherein an annealing temperature of the second conductive layer is higher than that of the first conductive layer; and performing annealing treatment on the layered structure at the annealing temperature of the first conductive layer to increase the surface roughness of the first conductive layer, thereby increasing the specific surface area of the second conductive layer. The present application further provides a chip electrode structure and a biosensing chip. In the present application, the first conductive layer having undergone annealing treatment is conducive to increasing the specific surface area of the chip electrode structure and reducing the electrochemical impedance.
A loading mechanism (200), a biochemical substance analysis apparatus (100) and a biochemical substance analysis system (1000). The loading mechanism (200) comprises a base (10), a mounting seat (20) and a loading platform (30). The base (10) comprises a supporting surface (11), and it is defined that a first direction (X) is perpendicular to the supporting surface (11). The mounting seat (20) is fixed on the supporting surface (11), and the mounting seat (20) is provided with a first guide slot (21), at least part of the first guide slot (21) being obliquely arranged relative to the first direction (X). The loading platform (30) is configured for placement of a first component (1) and a second component (2), and is movably arranged on the supporting surface (11) in the first direction (X). The second component (2) is provided with a first guide member (2b) slidably arranged in the first guide slot (21). The first guide slot (21) is configured to cooperate with the first guide member (2b), such that when the loading platform (30) moves in the first direction (X) towards the supporting surface (11), the second component (2) moves towards the first component (1) in a second direction (Y) perpendicular to the first direction (X) and is assembled with the first component (1).
B23P 19/04 - Machines for simply fitting together or separating metal parts or objects, or metal and non-metal parts, whether or not involving some deformationTools or devices therefor so far as not provided for in other classes for assembling or disassembling parts
B25B 27/00 - Hand tools or bench devices, specially adapted for fitting together or separating parts or objects whether or not involving some deformation, not otherwise provided for
A sample mixing device (100) and a sample mixing method. The sample mixing device (100) comprises a support module (1) and, disposed on the support module (1), a mixing module (2) and a blocking module (3). The mixing module (2) is configured to drive a sealed container (10) containing samples to make rotational motion. The blocking module (3) is configured to block the disengagement of the sealed container (10) from the mixing module (2) during the rotation. The mixing module (2) driving the sealed container (10) to make the rotation motion improves the mixing efficiency and mixing effect of the samples, and allows the samples to be less prone to cross-contamination in the sealed container (10). The provision of the blocking module (3) prevents the sealed container (10) from disengaging from the mixing module (2) by accident during rotary mixing, thereby improving the safety of uniform mixing.
A sample processing system and a biochemical reaction system. The sample processing system comprises a storage module, a transfer module, at least one incubation module and a control module; the storage module is configured to store a sample required for a biochemical reaction; the incubation module is configured to provide a preset temperature for the biochemical reaction; the transfer module is configured to transfer the sample; and the control module is configured to control the transfer module and the incubation module to work collaboratively. The sample processing system uses a modular design, can realize full-process automated sample processing, improves the efficiency and effect of sample processing, and is particularly suitable for automated preparation of single-molecule sequencing libraries.
Disclosed in embodiments of the present application are an instrument control method and apparatus, an electronic device, and a storage medium. The method comprises: in response to a control instruction configuration operation for a target instrument, displaying a control instruction configuration interface, and presenting, in the control instruction configuration interface, an instruction list to be configured; and in response to an instruction information configuration operation for the instruction list to be configured, obtaining an instrument control table corresponding to the target instrument, wherein the instrument control table comprises at least one instrument control instruction and an instrument execution action corresponding to the instrument control instruction, and the instrument control instruction is used for controlling the target instrument to execute the instrument execution action.
A filtering processing method and apparatus for gene sequencing signals, a device, and a storage medium. The method comprises: on the basis of current changes generated by different bases passing through a nanopore, obtaining a plurality of sets of raw gene sequencing signals; in a first-stage pipeline, performing filtering processing on each set of raw gene sequencing signals at the current time point to obtain preliminary gene sequencing signals; in a second-stage pipeline, storing the preliminary gene sequencing signals in a preset register, and performing filtering processing on the raw gene sequencing signals at the next time point to obtain candidate gene sequencing signals; and in a third-stage pipeline, storing the candidate gene sequencing signals in the register, and outputting the preliminary gene sequencing signals to a superordinate computer. The method can improve the filtering efficiency of gene sequencing signals.
G16B 40/10 - Signal processing, e.g. from mass spectrometry [MS] or from PCR
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
Provided are a gene sequencing data compression method and apparatus, and a gene sequencing data decompression method and apparatus. The gene sequencing data compression method comprises: on the basis of a sequence prediction model obtained by jointly training a sample base sequence and a corresponding sample quality value sequence, performing sequence prediction on at least one of a base sequence and a quality value sequence in gene sequencing data to be compressed, and performing entropy encoding on at least one of the base sequence and the quality value sequence on the basis of a sequence prediction result and a corresponding ground truth label to obtain compressed data of said gene sequencing data. The gene sequencing data decompression method comprises: on the basis of a sequence prediction model obtained by jointly training a sample base sequence and a corresponding sample quality value sequence, performing sequence prediction on gene sequencing data to be decompressed, and on the basis of a prediction result, obtaining decompressed data corresponding to said gene sequencing data.
The present invention relates to the technical field of biology, and in particular to a polynucleotide kinase mutant and a use thereof. The polynucleotide kinase mutant comprises, compared with a wild type polynucleotide kinase, at least one amino acid mutation in the following sites or functional equivalent sites: the 47th site and the 129th site; and the wild type polynucleotide kinase has an amino acid sequence as shown in SEQ ID NO: 1.
The present application relates to the field of biomedicine, and provides a base recognition method, a base recognition model training method, and an electronic device. The base recognition method comprises: inputting sequencing data into a pre-trained base recognition model, using a feature encoder of the base recognition model to acquire multiple encoded feature vectors of the sequencing data, and using a context network of the base recognition model to extract temporal information and contextual relationships of the multiple encoded feature vectors, thereby obtaining multiple contextual feature vectors having contextual association features, and then using a decoder to decode the contextual feature vectors, which can improve the accuracy of recognizing a base sequence from sequencing data. The base recognition model training method achieves algorithm development of the base recognition model by means of a pre-training + fine-tuning training approach. The use of the aforementioned method can reduce the training costs of the base recognition model and improve the accuracy of prediction of the model, thereby enhancing the accuracy of base recognition.
A liquid injection device, a liquid injection method, and a micro-fluidic system. The liquid injection device (100) has a liquid injection mode and a liquid supplement mode; in the liquid injection mode, a transmission liquid is injected into a first cavity (111), and then the transmission liquid acts on a first surface (311) and drives, by means of a first connecting part (33), a second sliding part (32) to slide, so that a reaction liquid in a fourth cavity (212) or the downstream section of the fourth cavity (212) is injected into a reaction device (200); and in the liquid supplementing mode, the transmission liquid is injected into a second cavity (112), and then the transmission liquid acts on a second surface (312) and drives, by means of the first connecting part (33), the second sliding part (32) to slide, so that the fourth cavity (212) or the downstream section of the fourth cavity (212) accommodates the injected reaction liquid. The area of the transmission liquid acting on the first surface (311) is greater than the area of the transmission liquid acting on the second surface (312), so that slow liquid injection and rapid liquid supplementation can be realized, and the slow liquid injection is beneficial to accurately and slightly controlling the liquid injection amount.
A nucleic acid molecule sequencing method of the present disclosure, comprising: first acquiring a sequencing image of a target nucleic acid sample; performing image processing on the sequencing image by means of an image processing model, so as to obtain a target image, the image processing model being a model obtained by training constructed nucleic acid molecule true value images and corresponding simulation nucleic acid images; and performing nucleic acid molecule sequencing on the basis of the target image, so as to obtain a sequencing result corresponding to the target nucleic acid sample.
Provided are a DNA polymerase, and a preparation method therefor and the use thereof. The DNA polymerase has less than 42% sequence similarity to Taq DNA polymerase, and has polymerase activity, higher thermal stability, 5'-3' exonuclease activity and inhibition resistance.
Disclosed are a terminal deoxyribonucleoside transferase mutant, a preparation method therefor and a use thereof. A wild-type terminal deoxyribonucleoside transferase is subjected to molecular modification, to improve modified nucleic acid monomer polymerization activity and modified nucleic acid monomer catalysis efficiency, and to realize efficient single-base addition efficiency. Multiple 3'-O-blocking modified dNTPs substrates can be added to a 3'-OH end of an oligonucleotide single chain without a template, so that a novel and effective tool enzyme can be provided for the enzymatic method from de novo synthesis of nucleic acid.
The present application provides an isolated polypeptide, a preparation method therefor, and use thereof. The polypeptide has an amino acid sequence that is at least 99% homologous with SEQ ID NO:1, and that is preferably 100% homologous therewith.
Disclosed in the present application are a method for determining a consensus sequence of nucleic acid molecules and the use. The method comprises the following steps: acquiring sequencing information of the nucleic acid molecules, wherein the sequencing information comprises multi-copy sequences of library molecules, and the library molecules comprise single-stranded circular molecules formed by ligation of the nucleic acid molecules and feature fragments; identifying feature sequences of the feature fragments in the sequencing information on the basis of a Levenshtein distance algorithm and by means of known sequences of the feature fragments; dividing the sequencing information according to the feature sequences, and determining repetitive nucleic acid sequences of the nucleic acid molecules; and generating the consensus sequence according to a set of the repetitive nucleic acid sequences of the nucleic acid molecules.
Embodiments of the present application belong to the field of genetic variation detection, and provide a genetic variation detection method and apparatus, a storage medium, and a computer device. The method comprises: by means of a high-quality single-base variation site measured by a model for performing genetic variation detection on the basis of gene accumulation, determining, from a reference haplotype set, a haplotype of a gene segment under test, and, on the basis of the haplotype, determining an insertion/deletion site of the gene segment under test.
The present application provides a nucleic acid array for detecting spatial information of nucleic acids in a sample, a method for detecting spatial information of nucleic acids in a sample on the basis of the array, and a method for producing the nucleic acid array.
Provided are a protein sequencing library construction method and a protein sequencing method. The protein sequencing library construction method comprises: using an endonuclease to carry out enzymatic cleavage on a target protein to obtain two or more polypeptide fragments each containing a free amino group at the N-terminus and the same functional group at the C-terminus, the functional group comprising an amino, ε-carboxyl or phenolic hydroxyl group; using the functional group at the C-terminus and the free amino group at the N-terminus to conjugate each polypeptide fragment to a nucleic acid to obtain a protein sequencing library, wherein the nucleic acid is conjugated to the functional group at the C-terminus and the free amino group at the N-terminus of the polypeptide fragment, respectively. The present invention can solve the problem in the prior art of the difficulty in sequencing of native proteins (i.e., proteins with unknown sequences), and is applicable to the field of protein sequencing.
Provided in the present application are an isolated polypeptide, a preparation method, and a use. The polypeptide has an amino acid sequence which is at least 91% homologous or 92% homologous or 93% homologous or 94% homologous or 95% homologous or 96% homologous or 97% homologous or 98% homologous or 99% homologous to SEQ ID NO: 1.
Provided are a single-cell chromatin accessibility and transcriptome joint sequencing method and a use thereof. The method comprises: using a transposase to process a nucleus so as to obtain gDNA of a chromatin open region linked to a first specific tag sequence; using a transcriptome capture sequence to process the nucleus so as to obtain cDNA linked to a second specific tag sequence; generating a droplet on the basis of droplet microfluidics to encapsulate the nucleus and a first microbead in the droplet, wherein the gDNA and the cDNA are captured by the first microbead, and one or more nuclei are encapsulated in the droplet; and sequencing the gDNA and the cDNA, and obtaining single-cell chromatin accessibility and transcriptome joint information on the basis of the first specific tag sequence and the second specific tag sequence.
The present invention provides a male infertility classification method and device and a method and device for constructing a related prediction model. The classification method comprises: using a contribution proportion of testis-related single-cell types in seminal plasma cell-free RNA as a feature to construct a male infertility prediction model; and inputting the contribution proportion of the testis-related single-cell types in the seminal plasma cell-free RNA of a sample to be tested into the male infertility prediction model to obtain a classification prediction result of the sample to be tested. The classification method can accurately predict male azoospermia and subtypes thereof of an unknown sample, and is more convenient to operate compared with a previous method. In addition, the method allows for prediction of the subtypes of azoospermia prior to clinical testicular biopsy, thereby achieving the objectives of non-invasive detection and diagnosis.
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
Provided are a T4 DNA ligase mutant and the use thereof. The T4 DNA ligase mutant: a) has an amino acid sequence having at least 80% identity to SEQ ID NO: 1; b) comprises a substitution of an amino acid at the position corresponding to position 28 of SEQ ID NO: 1; and c) has a T4 DNA ligase activity. The T4 DNA ligase mutant has improved double-end linker connection efficiency and single-chain cyclization performance, and is compatible with different reaction systems. The T4 DNA ligase mutant can be widely used in library construction for various high-throughput sequencing, single-chain cyclization and ligation of DNA fragments in molecular cloning.
Provided are a Ski2-like helicase and a use thereof. The Ski2-like helicase comprises: 1) a protein having an amino acid sequence as shown in any one of SEQ ID NO: 1 to 4; or 2) a protein in which at least one site in the 2A domain and/or the Ratchet domain of the amino acid sequence in 1) is replaced by cysteine or an unnatural amino acid, and/or at least one cysteine in any one or more domains of the 2A domain, WH domain, and Ratchet domain is deleted or replaced by a natural amino acid other than cysteine, and which has helicase activity for unwinding nucleic acids in the 3' to 5' direction. The described helicase can form stable channels, has the function of unwinding nucleic acids in the 3' to 5' direction, and can broaden the application scenarios for nanopore sequencing.
The present invention provides a polypeptide and protein sequencing method, a kit, and a use. The polypeptide sequencing method comprises: S1, attaching a target polypeptide to a nanopore; and S2, introducing a recognition molecule, which specifically recognizes a terminal amino acid of the target polypeptide, into a nanopore sequencing system, and under the action of an electric field, using an electric signal change generated during binding/disassociation of the recognition molecule and the target polypeptide to detect the terminal amino acid of the target polypeptide. The detection of a single amino acid is achieved by using a unique electric signal change generated during binding/dissociation of the recognition molecule and the recognized terminal amino acid of the target polypeptide.
The present invention relates to the technical field of biology, and in particular to a method for improving the H&E-stained image quality of a spatio-temporal chip, a reagent combination, a kit, and a device. The present invention provides a new mounting medium, which uses a simple reagent and corresponding process design, achieving the same effects of mRNA in-situ capture and comprehensive enhancement of mRNA diffusion as a glycerol mounting medium, and effectively solving the problems of fading and color diffusion after tissue staining. Registration of an H&E image and a spatio-temporal expression matrix of a BGI Stereo-seq chip provides possibility for high-precision subcellular-level omics analysis.
Provided are a nucleic acid-polypeptide-nucleic acid ternary complex, and a use thereof in polypeptide nanopore sequencing. The ternary complex has the following structural formula: single-stranded nucleic acid 1-polypeptide-single-stranded nucleic acid 2, the single-stranded nucleic acid 1, the polypeptide and the single-stranded nucleic acid 2 being covalently linked in sequence, the single-stranded nucleic acid 1 being used to connect with a sequencing adapter, the single-stranded nucleic acid 1 and/or the single-stranded nucleic acid 2 each independently further comprising an extension chain, the extension chain being disposed at either end or in the middle of the single-stranded nucleic acid 1 and/or the single-stranded nucleic acid 2, the extension chain comprising a chain formed from one or more of the following molecules in random order: nucleosides, nucleotides or organic linkers, and the extension chain not being a sequence of multiple nucleotides when it is located on the single-stranded nucleic acid 2. Extending the length of the single-stranded nucleic acid at at least one end of the polypeptide is beneficial for reducing the phenomenon of stutter generated during a polypeptide nanopore sequencing process.
An imaging system and method, an identification apparatus and method, a sequencer, and a sequencing method. The imaging system comprises: a laser light source and a structured light modulation element, the structured light modulation element being used for modulating an excitation light, so as to generate and emit a first light and a second light having separate optical paths; a light guide element, configured to, in a first angle state, guide the first light and the second light such that interference occurs on the surface of a test sample to form a fringe structured light, and in a second angle state, guide the first light or the second light to form a wide-field light on the surface of the test sample, wherein the fringe structured light excites and generates a structured light fluorescence signal, and when the light guide element emits the first light or the second light at the second angle, the first light or the second light forms a wide-field light spot on the surface of the test sample, so as to excite and generate a wide-field fluorescence signal; and an imaging module, used for acquiring the structured light fluorescence signal to generate a structured light image, and acquiring the wide-field fluorescence signal to generate a wide-field image.
The present invention provides a DNA polymerase mutant and a use thereof. The DNA polymerase mutant has DNA polymerization activity, and comprises an amino acid sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% homology with the amino acid sequence shown in SEQ ID NO: 1. The invention can solve the problem of low polymerization activity of wild-type DNA polymerases in the prior art, and is applicable in the field of DNA polymerases.
Provided in the present invention are a DNA polymerase and the use thereof. The above-mentioned DNA polymerase comprises: (a) a protein having a sequence as shown in SEQ ID NO: 1; (b) a protein having substitution, deletion, and/or addition of one or more amino acids at at least one of the following sites in the sequence as shown in SEQ ID NO: 1: D147, E149, L424, Y425, P426 and A503; or (c) a protein having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% or more homology to the sequence in (a) or (b), and having a DNA polymerase activity. The present invention can solve the problem of the limited types of DNA polymerases in the prior art, and is suitable for the field of DNA polymerases.
Provided are a transcriptome library construction method based on multiple displacement amplification, a kit used for said method, and a transcriptome sequencing method and a spatial transcriptome sequencing method based on this method. The method comprises: reverse-transcribing an mRNA molecule to obtain a cDNA chain; using the cDNA chain as a template, performing multiple displacement amplification under the actions of MDA primers and a DNA polymerase having chain displacement activity, to obtain multiple cDNA amplified fragments of different lengths, the cDNA amplified fragments constituting a transcriptome library, there being multiple MDA primers, and the MDA primers containing a first sequence used for sequencing and a second sequence used to bind to the cDNA chain, the second sequence being a random sequence, the second sequence randomly binding to the cDNA chain, and, optionally, the first sequence being a first linker, and the second sequence also containing degenerate bases.
The present application provides a multi-modal feature fusion method, a model training method, an electronic device, and a storage medium. The multi-modal feature fusion method comprises: inputting the obtained transcriptome information and imaging information into a preset multi-modal fusion model to obtain a multi-modal fusion feature, comprising: inputting the transcriptome information into a first single-modal feature extractor to obtain a transcriptome feature, and inputting the imaging information into a second single-modal feature extractor to obtain an imaging feature; performing attention mechanism-based information fusion on the transcriptome feature and the imaging feature, and concatenating the features into a feature vector; and encoding the feature vector and a spatial position map into a first latent variable on the basis of an auto-encoder of a graph generation model. The present application can improve the fusion performance of multi-modal features.
G06V 10/80 - Fusion, i.e. combining data from various sources at the sensor level, preprocessing level, feature extraction level or classification level
Provided are a method for constructing an RNA array, a kit for preparing an RNA array, a method and device for detecting RNA-protein interaction, and a kit. The method comprises: on the basis of a first nucleic acid fixed on a first chip, transcribing the first nucleic acid to obtain a target RNA chain; and on the basis of a second nucleic acid fixed on a second chip, capturing the target RNA chain by using the second nucleic acid, so as to obtain the RNA array.
Provided in the present invention are the construction and application of a polypeptide classifier. Specifically, provided in the present invention is a polypeptide classification method. The method comprises: a sequencing step, which comprises: sequencing a polypeptide to be tested or a linker containing said polypeptide, acquiring a sequencing signal of said polypeptide, and obtaining a spectrum signal of said polypeptide from the sequencing signal; a feature extraction step, which comprises: by means of a feature set function, respectively extracting a plurality of feature values from the sequencing signal and the spectrum signal, so as to form a feature set; and a prediction step, which comprises: inputting the feature set into a polypeptide classification model for classification, wherein a category with the highest frequency of occurrence among output categories is the category of said polypeptide. By means of the method of the present invention, nano-sequencing signals of more types of polypeptides can be more accurately classified, and the accuracy rate can reach 95.52%.
Provided in the present disclosure is an object detection model-based polypeptide signal extraction method. Provided in the present disclosure is a polypeptide signal extraction method, which comprises: obtaining from a sequencing sample an image containing a sequencing signal, the sequencing sample comprising a molecule under test having a polypeptide portion and a non-polypeptide portion (NPP), and the sequencing signal comprising a mixed sequencing signal having a polypeptide signal and a non-polypeptide signal (NPS); using a neural network model to identify the coordinates of a bounding box of the non-polypeptide signal in the image, and converting the coordinates into time index points in an original sequencing signal; and, by means of the time index points, extracting the polypeptide signal from the mixed sequencing signal.
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
89.
FLUID PATH AND USE METHOD THEREFOR, FLUID PATH SYSTEM AND USE METHOD THEREFOR, AND SEQUENCER
Provided are a fluid path and a use method therefor, a fluid path system and a use method therefor, and a sequencer. The fluid path comprises a first surface and a second surface; the first surface at least comprises an exposed chip surface; the first surface and the second surface are arranged at a preset distance; a preset position of the second surface is provided with a reagent fluid; and the second surface can move in a preset direction, and drive the reagent fluid at the preset position to be at least injected into a gap between the chip surface and the second surface. Movement of the second surface drives the reagent fluid to move, thus avoiding using pressure to drive the reagent fluid; the chip surface is in a static state, such that the average flow rate of the fluid path is half of the movement speed of the second surface, and the thickness of the fluid entering the gap will be at least twice the original thickness, thereby reducing the reagent thickness of fluid intake; and the fluid path is an open fluid path, and the first surface and the second surface do not need to be fixed by adhesive bonding, thus overcoming the technical challenge of sealing fluid paths under the condition of small gaps.
B05C 9/00 - Apparatus or plant for applying liquid or other fluent material to surfaces by means not covered by groups , or in which the means of applying the liquid or other fluent material is not important
90.
METHOD FOR MODIFYING SOLID-PHASE SUPPORT AND METHOD FOR CELL CAPTURE
Provided in the present invention is a method for modifying a solid-phase support. The solid-phase support is suitable for adhering to cells. The method comprises: bringing a solid-phase support into contact with a polylysine–protein factor mixed solution, wherein the polylysine–protein factor mixed solution comprises polylysine and a protein factor, and the protein factor comprises at least one of an extracellular matrix protein and a cellular integrin. In the method, by modifying the solid-phase support, a large number of cells can be captured by the solid-phase support, and the cells captured by the solid-phase support have clear outlines, such that the cell capture efficiency of the solid-phase support is improved.
The present application relates to a feature extraction method and apparatus for cell grouping, and a cell grouping method and apparatus. The feature extraction method for cell grouping comprises: performing disturbance on a cell feature matrix of a sample cell, so as to obtain a first feature matrix and a second feature matrix; performing disturbance on an adjacency matrix of the sample cell, so as to obtain a first adjacency matrix and a second adjacency matrix; by means of a feature encoder to be trained, performing encoding on a first image to obtain a first embedding matrix, and performing encoding on a second image to obtain a second embedding matrix; fusing the first embedding matrix with the second embedding matrix, so as to obtain a target embedding matrix; performing decoding on the target embedding matrix, so as to obtain at least one of a reconstructed cell feature matrix and a reconstructed adjacency matrix; and on the basis of at least one of a first difference and a second difference, iteratively optimizing parameters of said feature encoder until an iteration stop condition is met, so as to obtain a trained feature encoder, wherein the feature encoder is used for extracting features required for cell grouping.
G06V 10/44 - Local feature extraction by analysis of parts of the pattern, e.g. by detecting edges, contours, loops, corners, strokes or intersectionsConnectivity analysis, e.g. of connected components
92.
SINGLE MOLECULE DETECTION SYSTEM AND SINGLE MOLECULE DETECTION METHOD
A single molecule detection system and a single molecule detection method. The single molecule detection system comprises: a surface plasmon resonance (SPR) sensor (100), comprising a first surface (111) and a second surface (112), wherein the first surface (111) is configured to bind to a first molecule (610), and the first molecule (610) is configured to bind to a second molecule (620) marked with a fluorescent substance (621); a light source (200), configured to provide incident light to the second surface (112) to excite surface plasmon polaritons (SPP), so as to generate SPR; a first detection portion (300), configured to detect optical parameters of the SPR; and a second detection portion (400), configured to detect a fluorescence signal generated by the second molecule (620). On the basis of the resonance and fluctuation characteristics of the SPPs, a marked signal feature and an unmarked signal feature are synchronously obtained on two sides of a surface of the SPR sensor (100), so that qualitative or quantitative measurement of features such as loading amount, positioning, affinity to a substrate, and a molecular docking rate of the unmarked first molecule (610) is realized, and dynamic interaction processes between molecules such as binding and dissociation are synchronously measured.
G01N 21/27 - ColourSpectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection
Provided is a new reverse transcriptase or a biologically active fragment thereof. The reverse transcriptase or biologically active fragment thereof comprises a mutated sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identity to SEQ ID NO: 1, wherein the mutation comprises at least one of substitution, deletion and insertion.
Disclosed in the present invention is a method for constructing a sequencing library. The method comprises: (1) performing reverse transcription treatment on a mRNA to obtain a reverse transcription product without the need of adding a template switch oligo, the 3' end of the mRNA containing a poly-A sequence, the mRNA being connected to a chip, the chip being connected to a probe containing a poly-T sequence, and the connection being realized by means of the complementary pairing of the Poly-A sequence at the 3' end of the mRNA and the poly-T sequence on the chip; and (2) performing fragmentation on the reverse transcription product and ligating a first adapter to same so as to obtain a fragmentated and adapter-ligated product, the fragmentated and adapter-ligated product being connected to the chip; and (3) releasing the fragmentated and adapter-ligated product from the chip, so as to obtain a sequencing library.
A novel Cas12a nuclease BEST5 and a use thereof in gene editing and nucleic acid detection. The novel Cas12a protein, namely, BEST5, can be used in a nucleic acid detection system and can be used as a genome editing tool enzyme, providing more tools and effective site selection for in-vivo gene editing application.
Disclosed is a use of Lactobacillus gasseri TF08-1 in the prevention and treatment of Helicobacter pylori infection. The strain has the beneficial effect of inhibiting the proliferation of Helicobacter pylori and urease activity in vitro; in animal experiments, probiotics (live bacteria preparations) and postbiotics (inactivated bacteria preparations) thereof were able to effectively prevent and treat Helicobacter pylori infection, inhibit the proliferation of Helicobacter pylori in the body, and improve gastric mucosal damage and systemic inflammatory response caused by Helicobacter pylori infection.
A61K 35/747 - Lactobacilli, e.g. L. acidophilus or L. brevis
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A packaging device, a preparation method therefor and an electronic apparatus. The packaging device comprises a circuit board, a heat conduction block and an electronic element. The circuit board comprises a first surface and a second surface which are oppositely arranged in a first direction, and the circuit board is provided with a through slot passing through the first surface and the second surface. The heat conduction block is fixed on the circuit board and is at least partially located in the through slot. The heat conduction block comprises a third surface and a fourth surface which are oppositely arranged in the first direction, and the third surface is exposed out of the opening of the through slot at the first surface. The electronic element is fixed on the third surface. The electronic element comprises a central region and an edge region arranged around the central region. Viewed from the first direction, the third surface overlaps with the central region. The present application can improve the heat dissipation efficiency and the temperature uniformity of the surface of the electronic element.
A method for embedding a nanopore protein into a biomimetic membrane and the use thereof. The method comprises: preparing a biomimetic membrane of a multi-block copolymer, wherein the multi-block copolymer comprises a hydrophilic segment and a hydrophobic segment; and embedding a nanopore protein into the biomimetic membrane, wherein the multi-block copolymer comprises a copolymer of two or more blocks, the biomimetic membrane comprises an aromatic ring structure, the aromatic ring structure is linked between the hydrophilic segment and the hydrophobic segment of the multi-block copolymer, and/or the nanopore protein comprises an aromatic ring structure, and the aromatic ring structure is located on an amino acid in the transmembrane region of the nanopore protein facing the biomimetic membrane. By means of the method, the number of single pores and/or the single-pore retention rate of a biomimetic membrane during embedding can be improved.
B01D 71/82 - Macromolecular material not specifically provided for in a single one of groups characterised by the presence of specified groups, e.g. introduced by chemical after-treatment
99.
GENE EXPRESSION MATRIX OPTIMIZATION METHOD, ELECTRONIC DEVICE, AND STORAGE MEDIUM
Provided are a gene expression matrix optimization method, an electronic device, and a storage medium. The method comprises: acquiring cell data of a plurality of cells, wherein the cell data comprises an initial gene expression matrix of each of the plurality of cells; determining a preset number of nearest neighbor cells of a target cell among the plurality of cells on the basis of the cell data; determining a gene expression distance between the target cell and each nearest neighbor cell, determining a distance parameter on the basis of a target non-zero value among the gene expression distances, and determining, on the basis of the distance parameter, a weight parameter corresponding to each nearest neighbor cell; and on the basis of the weight parameter corresponding to each nearest neighbor cell and the initial gene expression matrix of each nearest neighbor cell, obtaining a target gene expression matrix obtained by smoothing of the target cell. By using the described method, the noise in a gene expression matrix can be reduced to improve the accuracy of performing downstream analysis on the basis of the gene expression matrix.
A biochip, a preparation method therefor and the use thereof. The biochip is a double-sided porous nano-biochip, which has an anodized nanostructure on the surface thereof; and the surface of the chip can be chemically modified to provide, for RNA synthesis, linking molecules required for a synthesis reaction, thus enabling the attachment of monomers to the surface of the biochip. The biochip can be prepared by using an anodization method which is easily operated and is low cost, thereby lowering the difficulty of the preparation process, and providing synthetic products having a higher loading capacity at a lower price.
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