2045 results about "Library" patented technology

The invention is applicable to the technical field of drug research and development, and provides a lead compound discovery method based on a large language model, which comprises the following steps: determining a target spot and constructing an initial compound library; generating fragments and forming an initial fragment library; calculating the frequency of occurrence of the fragments and the affinity contribution degree of the fragments to the target protein, and updating the fragment library; fragment sampling weight calculation and candidate fragment selection; the large language model generates molecules according to the candidate fragments; evaluating the quality of the generated molecules and updating the molecule library; and repeating the cycle until a preset iteration round number is reached. A fragment-based drug design method is combined with the large language model, rich domain knowledge of the large language model is used for replacing human experts to guide drug design, fragments are used as prompts to stimulate the internal potential of the large language model, the advantages of the two methods complement each other, exploration of the whole chemical space is completed, and the drug design efficiency is improved. The lead compound reaching the human expert level is designed in actual use, and a new technical means is provided for drug research and development.

The invention relates to the technical field of virus whole genome sequencing, and discloses a method for virus whole genome sequencing, which comprises the following steps: S1, extracting a sample genome, operating according to a specification of a commodity kit, extracting RNA (Ribonucleic Acid) of the sample genome, and performing library construction after reverse transcription and targeted amplification. According to the method for sequencing the whole genome of the virus, the whole genome sequence of the virus can be obtained through the sequencing method, and compared with the current detection which only stays at negative and positive detection, the whole genome sequence can be obtained on the basis through the method for sequencing, epidemiological traceability is carried out, and meanwhile the sequencing cost can be effectively reduced.

The present disclosure provides methods for reducing sequencing errors comprising one or any combination of: (i) removing deaminated bases in any nucleic acid molecule throughout a library preparation workflow which includes immobilised splints which bind to the library, the use of a compaction oligonucleotide, optionally with an intervening sequence, formation of closed circular nucleic acids, creating gaps using glycosylase and lyase activities at positions with deaminated bases. The library may be sequenced using pairwise sequencing, e.g. with dark sequencing and / or sequencing using a multivalent labelled probe for the formation of an avidity molecule and soluble primer and polymerase. Method for sequencing concatemers in which the concatermers are contacted with polymerases, soluble primers and a multivalent labelled molecule which forms a complex with the polymerase. Detecting polymerase position and nucleobase bound to the polymerase in the complex. These methods generate higher quality base calls during downstream sequencing workflows.

The invention provides a nucleic acid aptamer for specific recognition of morphine and application of the nucleic acid aptamer, and belongs to the technical field of biosensing and detection. The nucleotide sequence of the nucleic acid aptamer is as shown in SEQ ID NO: 1. The screening method is based on a Capture-SELEX technology and comprises the key steps that streptavidin magnetic beads are used for fixing an ssDNA library, estradiol, deabietic acid and totarol are introduced to serve as reverse screening substances so as to remove non-specific sequences, and finally the high-specificity aptamer is obtained through high-throughput sequencing and affinity determination. The dissociation constant of the aptamer and morphine is 127.31 nM, and the aptamer shows high affinity and high specificity. The invention further relates to application of the aptamer in preparation of a sensor and a kit for detecting morphine, and a new technical means is provided for rapid detection of morphine.

Provided herein are fusion polypeptides comprising an amino acid sequence of a bacteriocin, the amino acid sequence of the bacteriocin being a cleavage intein both on both the N-terminus and on both the C-terminus that cyclizes the bacteriocin. Also provided are nucleic acids and genetic vectors encoding the fusion polypeptides, as well as microbial cells genetically engineered with the nucleic acids or genetic vectors. Also provided are methods of making the cyclic bacteriocin, methods of screening using a library of nucleic acids or genetic vectors encoding the fusion polypeptides, and methods of controlling growth of organisms using the cyclic bacteriocin made by the methods provided herein.

The invention provides a method for deducing the abundance of each family in a group based on mixed pool simplified genome sequencing, which comprises the following steps of: (1) establishing a parent 2b-rad library, and extracting SNP (Single Nucleotide Polymorphism) genotypes and sites by using a 2b-rad standard process; combining the SNP genotypes of the 2n parents into genotypes of n parent pairs according to a male parent and female parent relationship; comparing the genotypes of the parent pairs, and determining family specific tags; (2) extracting offspring individual tissues, mixing, and carrying out DNA extraction and 2b-rad library building sequencing on the mixed sample tissues; counting the sequencing depth of all the specific tag sites and calculating the secondary allele frequency of the specific tag of the mixed sample filial generation; and (3) calculating the proportion of each family in the offspring according to the sequencing depth of the specific tag site and the secondary allele frequency of the specific tag of the mixed offspring. According to the method, the overall feature distribution of the family can be accurately evaluated without sequencing each individual, so that the cost is greatly reduced.

The invention relates to a method for carrying out pathogenic microorganism identification and gene variation state joint detection on a pulmonary alveolar lavage fluid sample based on high-throughput sequencing. The method comprises the following steps: extracting nucleic acid from the pulmonary alveolar lavage fluid sample; constructing a metagenome capture library, and constructing a lung cancer polygene library; carrying out final library pooling; performing high-throughput sequencing; and analyzing data. Compared with the prior art, the scheme provided by the invention is based on a technical path of'macro 'captured by metagenome and'target' of targeted high-throughput sequencing; after the constructed final library is subjected to high-throughput sequencing and data analysis, index output (pathogenic microorganism identification, host chromosome copy number variation, gene mutation, gene fusion, gene copy number variation and methylation state) of multiple biomarkers can be met in one-time detection.

The invention discloses a bidirectional reversible conversion method and system between a peptide molecule SMILES and a sequence expression. The core innovation lies in that a new sequence description syntax is defined to retain information of a polypeptide special bond and specific modification of amino acid; a main chain atom index and adjacency traversal topology identification algorithm is adopted, and end group and topology integrated detection and coding are carried out; a residue recognition algorithm for main chain cutting and template library matching is compatible with any standard or non-standard amino acid residues, an extensible end group library / monomer template library and an automatic increment mechanism, and automatic recognition and sequence annotation of S-S disulfide bonds; the invention relates to a high-fidelity assembly algorithm of HELM anchor points and topology aware cyclic peptide processing. The method solves the problems of incapability of supporting a complex polypeptide topological structure, poor reversibility, insufficient expansibility of a monomer library and the like in the prior art, can be widely applied to scenes of quantitative structure-activity relationship model construction, large-scale polypeptide data cleaning and the like, and has remarkable practicability and innovativeness.

The invention discloses preparation of a human CD56 immune phage display antibody library, which comprises the following steps: S1, animal immunization: expressing recombinant hCD56 protein in escherichia coli, then immunizing a Balb / c mouse, and detecting immune titer; s2, splenocyte preparation: extracting RNA (Ribonucleic Acid) of immune mouse spleen cells, and performing reverse transcription to obtain cDNA (Complementary Deoxyribonucleic Acid); s3, preparation of an initial bacteriophage display library: amplifying a heavy chain variable region and a light chain variable region by using a PCR technology, and then assembling to form scFv; constructing scFv phagocytids, electrically transforming the scFv phagocytids into TG1 competent cells, and constructing a bacterial library; s4, constructing a phage single-chain library of the hCD56: infecting the bacterial library by using a helper phage M13K07, and constructing a phage single-chain antibody library; and S5, elutriation and screening of a phage library: specifically enriching a phage single-chain antibody library, screening positive clones from the phage single-chain antibody library, and determining a sequence. According to the invention, the human hCD56 antibody scFv sequence fragment can be screened out, and the research and development period is shortened.

The invention belongs to the field of preparation of medical intermediates, and particularly relates to a preparation method of an On-DNA sulfinic acid structure compound. The method for preparing the On-DNA sulfinic acid structure compound comprises a step of oxidizing On-DNA thiol (phenol) into the On-DNA sulfinic acid structure compound under alkaline and heating or illumination conditions, a solvent used in the reaction step is a mixed solution of water, dimethyl sulfoxide, N, N-dimethylformamide, acetonitrile, ethanol or tetrahydrofuran, the reaction temperature is not more than 80 DEG C, and the reaction time is not more than 2 hours. And the illumination wavelength ranges from 365 nanometers to 535 nanometers. The On-DNA sulfinic acid structure compound obtained in the invention can be directly used for constructing a structure compound with a sulfonyl group, the reaction condition is mild and convenient, a new method and a new idea are provided for construction of a DNA coding compound library, and the On-DNA sulfinic acid structure compound has a very good application prospect in lead drug development.

The present disclosure relates in some aspects to methods for analyzing target nucleic acids and their spatial locations in a biological sample using Argonaute proteins. In some aspects, a barcode probe library comprising a plurality of probes each comprising a plurality of barcode subunits that identifies a target analyte is detected in situ in the sample. Also provided are compositions and kits for use in accordance with the methods.

Disclosed herein is a system for detection of a molecular community in a molecular network, the system comprising an information handling system that comprises at least one processor; and a non-transitory storage medium storing instructions readable and executable by the processor to perform a method comprising receiving molecular data from an analytical device and / or a data repository; generating an unpruned molecular network from the molecular data; treating the unpruned network with a community detection algorithm to form one or more molecular communities; parsing the molecular communities to prevent the formation of singletons; and identifying at least one molecule present in the molecular community by comparing the molecular community with reference spectra from a library of spectra or by using a molecular structure prediction tool.

Disclosed are methods of preparing a sequencing library to quantify tRNA abundance and tRNA modifications in an RNA sample that comprises contacting RNA with oligonucleotides in the presence of a ligating agent and performing nanopore direct sequencing. It also discloses a kit to perform said method.

The invention discloses a recombinant fusion protein of a human lambda light-chain single-chain antibody, a DNA (deoxyribonucleic acid) molecule, a library building method and application, and the recombinant fusion protein of the human lambda light-chain single-chain antibody is the recombinant fusion protein formed by connecting the human lambda light-chain single-chain antibody, phage Piii protein and luciferase, the amino acid sequence of the recombinant fusion protein of the human lambda light-chain single-chain antibody is shown as SEQ ID NO: 5, the recombinant fusion protein library of the human lambda light-chain single-chain antibody has large capacity, the established single-chain antibody TG1 library is more than 1 * 10 < 9 > cfu / mL, positive clones capable of being combined with ligands can be screened and enriched for multiple rounds, and the recombinant fusion protein library has the characteristics of high sensitivity, high signal-to-noise ratio and the like.

The invention relates to a nano antibody Nb3-18 capable of identifying and neutralizing SFTSV (swine fever with thrombocytopenia syndrome), which comprises three complementary determining regions CDR1-3, and the sequences of the three complementary determining regions CDR1-3 are respectively shown as SEQ ID NO: 1-3. Nanometer antibody drug development and diagnostic kit research and development are carried out on SFTSV which is high in fatality rate but lacks effective vaccines and specific antiviral drugs, the nanometer antibody VHH which is specifically combined with GN is screened through the platform technology of preparing GN protein, inactivating viruses, immunizing alpaca, displaying nanometer monoclonal antibodies through a phage library and the like, the CDR sequence of the nanometer antibody VHH is identified, and the SFTSV with the high fatality rate is obtained. A humanized antibody Nb3-18 is constructed; meanwhile, the curative effect of Nb3-18 in treating SFTSV infection is evaluated at the in-vitro cell level. The invention provides a potential nano antibody new drug for clinical treatment of SFTSV, and also provides a corresponding detection kit for diagnosis of SFTSV.

The invention provides a probe set and method for detecting respiratory tract infection pathogenic microorganisms and application of the probe set and method. The probe group is high in specificity and sensitivity, capable of accurately capturing target species in a pathogen spectrum and efficiently enriching the target species, meanwhile, few library fragments of non-target species are introduced, pathogenic microorganisms are convenient to identify, the detection sensitivity is high, the accuracy is good, the time cost is saved, the coverage degree is wide, and the application prospect is wide. Various bacteria, fungi, viruses and other pathogenic microorganisms related to respiratory tract infection can be covered.

The invention discloses a multi-subtype influenza A virus nucleic acid detection kit and a detection method, and relates to the technical field of medical detection.The kit comprises a group of reverse transcription RT-RPA amplification primer pairs used for amplifying influenza A virus M gene target sequences, the reverse transcription RT-RPA amplification primer pairs are designed for specific areas of subtypes H1N1, H2N2, H3N2, H5N1 and H7N9, and the reverse transcription RT-RPA amplification primer pairs are designed for specific areas of subtypes H1N1, H2N2, H3N2, H5N1 and H7N9; the crRNA library comprises a plurality of crRNA molecules which are respectively complementary with different conserved regions in the M gene target sequence and is used for guiding Cas12a protein to carry out specific recognition; a Cas12a protein reagent; the reporter molecule can be subjected to non-specific cleavage by the Cas12a protein; the enzyme preparation, the buffer solution and the nucleotide substrate are required by RT-RPA reaction. The invention aims to realize synchronous, rapid, high-sensitivity and high-specificity detection of various subtype influenza A viruses.

The invention provides an intratumoral bacterium detection and analysis method based on circular DNA enrichment sequencing and related model construction, and belongs to the field of molecular biology. The intratumoral bacterium detection method provided by the invention comprises the following steps: extracting total DNA of cancer tissue or para-carcinoma tissue, carrying out linear digestion, purifying a linear digestion product, and enriching to obtain circular DNA; the method comprises the following steps: amplifying circular DNA, and breaking a DNA amplification product to 300-500bp; purifying DNA fragments, constructing a library, and sequencing; and performing genome comparison according to a sequencing result to obtain information of the intracellular bacteria. According to the method, complete bacterial genome and plasmid genome information can be captured, and the detection sensitivity of the intracellular bacteria and the richness of the bacterial genome information are improved. The invention further provides an intratumoral bacterium analysis method which can be used for screening generic cancer bacterial markers, and provides a cancer risk assessment machine learning model based on the intratumoral bacterium, so that the clinical application possibility of the intratumoral bacterium is improved.

The invention discloses a deoxyribozyme probe for identifying carbapenem-resistant klebsiella pneumoniae and application of the deoxyribozyme probe, and belongs to the technical field of deoxyribozyme probes. The method comprises the following steps: firstly, mixing a phosphorylated library chain, a substrate chain and a connecting chain, then, carrying out covalent linkage to construct a DNA library, firstly, carrying out reverse screening, separating and purifying a DNA band of an uncut substrate RNA site, constructing a chain-shaped DNA library by using the obtained DNA band, carrying out forward screening, separating and purifying the DNA band of the cut substrate RNA site, carrying out PCR (Polymerase Chain Reaction) amplification, and recovering a positive-sense chain, so as to obtain the DNA library. The deoxyribozyme probe is obtained by performing repeated screening and enriching, and the probe can recognize carbapenem-resistant klebsiella pneumoniae with high specificity and has the potential of exerting advantages in the aspect of biosensing application.

The invention provides a viral genome splicing method and system combining a reference sequence and de novo splicing, and the method comprises the steps: carrying out the quality control of the sequencing data of a viral genome sequence, and removing a host genome sequence in the sequencing data based on a k-mers strategy; splicing the sequencing data from the beginning to generate a preliminary assembling sequence of the viral genome; performing virus classification annotation on the virus genome preliminary assembly sequence based on a blastn tool, and selecting a highly similar virus genome sequence from a virus library as a reference sequence according to the virus classification annotation; generating a data set according to the reference sequence and the virus genome preliminary assembly sequence, dividing a plurality of sequence clusters according to the similarity between the sequences in the data set, and generating a consensus sequence; comparing the reads after the host is removed with a consensus sequence, and adjusting the consensus sequence according to a comparison result to obtain a final virus genome sequence. According to the method, the accuracy of virus genome splicing is improved, and the universality is high.

The invention discloses a tiny residual focus detection method and system based on ultra-high depth sequencing, and relates to the technical field of tiny residual focus intelligent detection.The tiny residual focus detection method comprises the following steps that on the basis of a sequencing library, splitting is conducted according to a sample index to obtain a to-be-detected sample, and a consensus sequence is obtained according to a molecular identifier of the to-be-detected sample; based on a consensus sequence, filtering out the consensus sequence of which the mass value is less than 25 or the family size is less than 3, and combining a variation type and a distance from a fragment edge as noise introduced into an original nucleic acid molecular chain; a context sequence (context) and a chain direction are used as noise for introducing the capture level of PCR amplification; on the basis of the noise level, the circulating tumor DNA level is estimated in combination with tumor priori knowledge, and the MRD state is determined by detecting the significance of molecular signal sources. According to the invention, the sensitivity and specificity of MRD detection are improved.

The present disclosure provides compositions, apparatus and methods for conducting separate sequencing batches on a support having nucleic acid template molecules immobilized thereon, where the separate sequencing batches can be conducted using any massively parallel sequencing technology. In some embodiments, a plurality of sub-populations of nucleic acid template molecules are immobilized to the support including at least a first and second sub-population. In some embodiments, the first sub-population of template molecules undergo first batch sequencing reactions and a region of the support is imaged to detect the first sequencing reactions, wherein the second sub-population of template molecules do not undergo sequencing reactions. In some embodiments, the second sub-population of template molecules undergo second batch sequencing and the same region of the support is imaged to detect the second sequencing reactions, wherein the first sub-population of template molecules do not undergo sequencing reactions.

The invention discloses a method and system for detecting respiratory tract pathogens, pathogen drug-resistant genes and pathogen virulence genes, and relates to the technical field of gene detection.The method comprises the steps that a respiratory tract sample of a patient is collected, DNA and RNA are extracted, and total nucleic acid is obtained; carrying out first-round PCR amplification on the total nucleic acid, purifying a first-round PCR product, carrying out second-round PCR amplification, and sorting the product to obtain a library building product; performing high-throughput sequencing on the library building product to obtain sequencing data, and detecting pathogens, drug-resistant genes and virulence genes; according to the method and system for detecting the respiratory tract pathogens, the pathogen drug-resistant genes and the pathogen virulence genes, by optimizing library preparation and direct library building of nucleic acid, the process is simplified, and efficiency and accuracy are improved; the balance reagent design guarantees library quality; the kit adapts to pathogen detection requirements in Yunnan and the like, provides efficient diagnosis, shortens detection time, improves treatment effect, regularly updates pathogen information, and keeps technical frontier.

The invention provides a beet genetic diversity analysis method based on whole genome re-sequencing. The method comprises the steps of PacBio HiFi library construction, computer sequencing, data information analysis, assembly quality evaluation and Hi-C auxiliary genome assembly. The invention further provides application, and the high-continuity beet reference genome is used for analyzing beet intraspecific genetic diversity and developing high-density molecular markers. According to the method, the high precision of HiFi, the super-long read length of Nanopore and Hi-C space interaction data are combined for the first time, the problems of repeated sequence and complex SV analysis are solved, and all-round breakthrough of genome continuity, annotation integrity, genetic diversity coverage and epigenetic integration is achieved.

The invention discloses a corn ZmMYBR37 gene and an application of the corn ZmMYBR37 gene in regulating and controlling the size of corn kernels. The nucleotide sequence of the ZmMYBR37 gene is as shown in SEQ ID No: 1 in a sequence table. A mutant material with small grains and reduced hundred-grain weight is separated from a corn EMS mutant library, and a mutation site occurs on a function unknown gene ZmMYBR37, so that protein translation is terminated in advance. The information analysis finds that the gene coding protein has a conservative MYB structural domain, and the gene coding protein is speculated to belong to an MYB transcription factor family. Gene expression analysis finds that the gene is high in constitutive expression in corn and high in expression level in leaves and embryos. The corn material overexpressed with the ZmMYBR37 has the advantages that the grain size is increased, and the hundred-grain weight is obviously increased, so that the ZmMYBR37 has the potential of increasing the corn yield.

The present disclosure provides compositions comprising nucleic acid partially double- stranded splint adaptors, and methods for preparing nucleic acid libraries using the partially double-stranded splint adaptors. The partially double-stranded splint adaptors can be ligated to double stranded nucleic acid fragments to form library-splint complexes having double stranded nicks, where the nicks can be ligated to form covalently closed circular molecules, which can then be subjected to downstream amplification and sequencing workflows.

The invention belongs to the technical field of molecular biology breeding, and particularly relates to application of a GhDCP5L gene in creation of high-temperature response cotton germplasm, and an amino acid sequence of a protein coded by the GhDCP5L or a homologous gene thereof is as shown in SEQ ID NO.2 or SEQ ID NO.4. The invention provides a novel thermal response gene, a gene resource library of high-temperature response of cotton is enriched, the GhDCP5L gene and a homologous gene thereof are applied to plant genetic engineering breeding, and new germplasm of high-temperature-resistant or sensitive high-temperature-resistant cotton can be accurately created by regulating and controlling the expression of the gene, so that the high-temperature-resistant or sensitive high-temperature-resistant cotton is obtained. The method provides technical support for coping with stable yield of cotton under the background of global warming climate, can be used for preparing male sterile line cotton germplasm by performing high-temperature treatment on the high-temperature-sensitive material, has good application value in the aspects of cotton hybrid seed production, promotion of hybrid cotton development and the like, and is beneficial to improving the economic benefit of the cotton industry.

The present application discloses a specific DNA fragment for sex identification of Pelteobagrus ussuriensis and a method for sex identification, specifically relating to the technical field of sex identification of Pelteobagrus ussuriensis. The above-mentioned identification method includes the following steps: Dissect 5 female and 5 male Pelteobagrus ussuriensis of a full-sib family to determine the physiological sex; respectively extract DNA from the muscles of female samples and male samples, construct a paired-end genomic DNA library with an insert fragment size of 300 bp, and perform high-throughput sequencing; based on the GWAS and Fst methods, identify that the sex chromosome of Pelteobagrus ussuriensis is chromosome 8, and then screen for Indels within the sex determination region on chromosome 8; screen a 601-bp male-specific DNA sequence and design and synthesize primers; use PCR amplification and agarose gel electrophoresis detection, and the result without specific bands is female, and the one with a 356-bp band is male. This scheme has the advantages of strong specificity, simple primer composition, and more intuitive identification of the sex of Pelteobagrus ussuriensis.

The invention provides a calculation method and system for accurately identifying heterozygosity deficiency in antenatal diagnosis, and is applied to the technical field of medical data processing. According to the method, the bam file and the variation information are obtained through whole-genome library building and sequencing analysis and data processing. SNP sites are screened, allele mutation frequency is calculated, and effective sites are screened. Dividing a genome window, calculating a homozygous rate HR value, and constructing a nonlinear weight reference based on a normal sample; and finally, an improved CBS algorithm is combined with weight reference to identify a significant AOH section, a table containing position and HR mean information is generated, heterozygosity deletion identification is completed, extra CMA detection is not needed, and the method is accurate and efficient.