60 results about "Host genome" patented technology

The invention provides an IBS micro-ecological transplantation intelligent prediction method and system based on multi-omics driving, and relates to the technical field of biomedicine. The method comprises the following steps: establishing a multi-omics data fusion subsystem to collect metagenome, metabolome, host genome and clinical phenotype group data of a target patient; inputting the data into a flora-metabolite combined network analysis model to construct an interaction network and extracting features; generating an incidence matrix based on the features and the host genome data and calculating indexes; generating indexes through a dynamic response algorithm in combination with the clinical phenotypic data and the indexes; and outputting a curative effect prediction result by using a transfer learning framework combined with modeling. The system comprises a data acquisition module, a network analysis module, a correlation calculation module, a dynamic response module and a joint modeling module. According to the method, multiple omics data are integrated, the flora and host relation is accurately mined, intelligent prediction of the micro-ecological transplantation curative effect is achieved, powerful support is provided for IBS personalized treatment, and meanwhile data processing and safety guarantee measures are taken.

A stable transformant, in which a gene of interest is incorporated into the genome, is simply and efficiently produced.A method for producing a transformant, comprising a step of introducing into a host, linear genome-introduced nucleic acid fragment(s) comprising a gene of interest and a helper plasmid for transformation having a pair of homologous recombination sequences for incorporation of the linear genome-introduced nucleic acid fragment(s), and then selecting a transformant, in which the gene of interest is incorporated into the predetermined position in the host genome and the gene of interest is expressed therein.

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 present disclosure relates to siRNA for inhibiting hepatitis B virus and uses thereof. In particular to an oligonucleotide for inhibiting HBV or a pharmaceutically acceptable salt thereof, the oligonucleotide comprises an antisense strand, the antisense strand comprises at least one modified nucleotide, and the nucleotide sequence of the antisense strand comprises a sequence or fragment as shown in any one of SEQ ID NO: 3-35. According to the present invention, the siRNA provides significant inhibition effects for HBsAg, HBV DNA and HBeAg generated by cccDNA and host genome integrated HBV DNA in vivo and in vitro, the drug effect is lasting, and compared with the original sequence, the optimized sequence improves the inhibition effect and the drug effect period, and reduces the off-target toxicity;

Methods and compositions for modulating a target genome are disclosed. This disclosure relates to novel compositions, systems and methods for altering a genome at one or more locations in a host cell, tissue or subject, in vivo or in vitro. In particular, the invention features compositions, systems and methods for inserting, altering, or deleting sequences of interest in a host genome.

The invention discloses a multi-modal constraint industrial microorganism promoter intelligent regulation and control system and method.The system comprises a modeling module, a parameter self-adaption increment optimization module and a generation optimization module, a multi-modal constraint promoter fusion model is constructed, a lightweight increment learning engine is utilized, and a multi-modal constraint industrial microorganism promoter fusion model is established; dynamically updating experimental data parameters of a small amount of promoters in a key layer of the multi-modal constraint promoter fusion model, and simulating potential regulation and control rules of a new host by utilizing a generative adversarial network to obtain biological compatibility constraints; introducing a double constraint mechanism of explicit rule injection and implicit adversarial optimization to execute biological constraint enhancement training; according to the method, host genome constraints and process environment parameters are dynamically coupled in the whole process of promoter identification, strength prediction and generation, so that a generated promoter feature sequence not only meets biophysical rules, but also can adapt to dynamic requirements of an actual fermentation scene. According to the method, the influence of cross-species data scarcity, environmental dynamic interference and biological compatibility risk on design precision can be remarkably reduced.

Nucleic acid error suppression is provided. In various embodiments, DNA is extracted from a collection of plasma samples. A sequence library with duplex adapters is prepared by ligating a duplex adapter having a Unique Molecule Identifier (UMI) to an end of each of a plurality of strands of the extracted DNA and amplifying the extracted DNA with a first polymerase chain reaction (PCR). A subset of the whole genome library is selected and amplified with a second PCR to increase an amount of PCR duplicates. A plurality of duplex reads is sequenced from the amplified subset aligned to a host genome and denoised based on said alignment. A variant presence is detected in at least one of the plurality of duplex reads. A signature of the variant is determined, which is compared to a collection of disease-specific variant signatures. A disease type is determined based on the comparison.

The invention discloses a qualitative and quantitative detection method for the integrity of an AAV vector under multi-primer ITR design, and the detection method comprises the following steps: S1, designing a plurality of primers in a conserved region of an ITR sequence of the AAV vector, the length of the primers being 18-25bp, the Tm value being 55-65 DEG C, and the GC% being 40-60%; s2, carrying out validity inspection on the primer; s3, adopting a Multiplex LAM-PCR (Polymerase Chain Reaction) method, performing amplification and sequencing by using the primer to obtain a chimeric sequence of the ITR and the host genome screened by using a biological analysis method, namely obtaining information of an ITR breakpoint; s4, according to the information of the ITR breakpoints, carrying out statistics on the distribution condition of the ITR breakpoints in the ITR region to obtain a statistical table; and S5, obtaining a qualitative and quantitative result of the ITR fracture position according to the statistical table. According to the method, the number of chimeric sequences in each primer region is counted, and the ITR breakpoints are qualitatively judged and quantitatively analyzed, so that the integrity of the AAV vector is comprehensively evaluated.

The invention discloses an astragalus sinicus breeding genetic data mining system based on bioinformatics, and particularly relates to the technical field of data mining. The method comprises the following steps: acquiring and synchronizing original sequencing data of an astragalus sinicus host genome and a rhizobium symbiotic microorganism genome to generate a standardized genetic information data set; the method comprises the following steps: identifying sequence cross contamination sites between a host genome and a symbiotic microorganism genome, and eliminating genetic information interference of a microorganism source, so as to obtain purified host genome data without microorganism interference; analyzing the contribution degree of the microbial genome to the target character of the astragalus sinicus to obtain a microbial effect weight; integrating the purified host genome data and the microbial effect weight, constructing an astragalus sinicus character association analysis model, and positioning character association sites; and finally, screening candidate breeding markers based on character associated site information to obtain a precise breeding genetic marker set. According to the method, the accuracy and efficiency of milk vetch breeding are improved.

The invention discloses a method, a system, equipment and a medium for detecting an HPV (human papilloma virus) DNA (deoxyribonucleic acid) integration event, and relates to the technical field of gene detection. According to the method, HPV types and virus loads (Ct values) pre-screened by qPCR are used as natural identifiers to guide grouping and mixing of samples, and HPV integrated event detection and sample tracing are synchronously realized through single sequencing. Clinical verification shows that compared with qPCR, the comprehensive sensitivity reaches 97.1%, and the cost is reduced by 60%. And a built-in targeted retest mechanism improves the reliability of a detection result. The invention provides a novel, traceable, economical and feasible solution, is used for high-throughput HPV-host genome integration feature analysis, balances cost, expandability and clinical accuracy, and provides a high-throughput and low-cost solution for HPV-related cancer screening.

The application provides a quality control for detecting respiratory pathogen nucleic acid, which comprises any one or more of the following respiratory pathogens: coronavirus, influenza virus, adenovirus, Mycoplasma pneumoniae, Streptococcus pneumoniae, rhinovirus or / and Legionella pneumophila. The full-length genome sequence of the coronavirus is divided into 6 target fragments, each with a length of 4000-5500 bp. The quality control of the application covers all detection target sequences (or target points) of the coronavirus, has a wide coverage, comprehensively detects target points, and does not have the phenomenon of missed detection. The quality control of the application contains main respiratory pathogen infections, has a wide range, and uses real virus samples and lentivirus samples as raw materials, and has more accurate detection target points. The preparation of the coronavirus quality control of the application integrates the target gene sequence into the host genome through the lentivirus vector, knocks out the self-replication gene in the preparation process, and has a "self-inactivation" ability, so that the recombinant lentivirus cannot replicate in the target cells and infect other cells.

The present invention belongs to the field of genetic engineering and enzyme engineering, and relates to a chassis strain lacking the bglS gene and its application. The present invention provides a genetically engineered chassis strain of Bacillus subtilis, wherein the chassis strain is constructed by deleting the glucanase encoding gene on the Bacillus subtilis host genome. bglS The described chassis bacteria can efficiently express alkaline protease, aminopeptidase, mesophilic α-amylase, and thermostable α-amylase. This method is also suitable for increasing the expression of other exocrine proteins, laying the foundation for efficient expression of heterologous proteins and promoting the efficient expression and industrial production of alkaline protease, aminopeptidase, mesophilic α-amylase, and thermostable α-amylase.

Provided is a method for preparing a random sgRNA full-coverage group of a target sequence. The method comprises: cleaving a PAM region of a target sequence using a restriction enzyme; linking same to an sgRNA skeleton; acquiring a sequence targeting a protospacer region by means of a restriction enzyme site having a collateral activity on the sgRNA skeleton; linking same to a T7 promoter; acquiring an sgRNA library with the T7 promoter by means of amplification; and acquiring an sgRNA library of the target sequence by means of in-vitro transcription. Also disclosed are a method for preparing an sgRNA library of ribosomal RNA, a method for removing ribosomal RNA from the RNA library, and a method for removing human whole genomes from a host genome. The method has the advantages of low cost, simple manufacture, uniform coverage, low preference, no limitation on the length of a target sequence, no need for design of sgRNAs in large quantities, etc.

The application discloses circular RNA and application thereof in pigeon trichomonad vaccine. The circular RNA comprises a coding element capable of encoding recombinant pigeon trichomonad AP33 or AP65 protein. The coding element has a sequence shown in SEQ ID NO. 1 or SEQ ID NO. 2 or a conservatively variant sequence thereof. The circular RNA can induce protein expression and generate high-level antibodies in an animal body. When the circular RNA is applied to the pigeon trichomonad vaccine, the circular RNA does not contain infectious worm component, can be degraded into nucleotides in the body, cannot be integrated into a host genome, has no risk for pigeons, can stimulate pigeons to generate a stronger immune response, including humoral immunity and cellular immunity, and can effectively resist parasitic infection. Meanwhile, the vaccine has high stability, the vaccine of the application can be prepared on a large scale through a molecular technology, and production cost is low.

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

The invention discloses a novel codon optimization method based on precise transcriptome sequencing and analysis thereof, and belongs to the technical field of bioinformatics. In order to improve the expression quantity of a target gene, corresponding accurate transcriptome data is obtained according to the development period of transgenic expression and parts such as tissues and organs, and efficient expression genes are screened to serve as a host genome expression library; the expression abundance of the gene is comprehensively considered when the use frequency of the codon of the host genome is determined, and the gene optimized by the novel codon optimization method increases the stability of the insecticidal protein gene RNA and improves the expression level of the protein. The invention provides better reference for gene modification and transformation, and provides a novel codon optimization method for high-efficiency expression of transgenes in plants.

The invention provides a genetic engineering strain, a construction method of the genetic engineering strain and application of the genetic engineering strain in biosynthesis of 5-hydroxytryptophan. According to the engineering bacterium, four key modules required by 5-HTP synthesis are sequentially introduced into a host genome in a genome integration mode through a CRISPR technology, and the four key modules comprise an aroGfbr-ppsA-tktA module for enhancing chorismate precursor supply, a trpEfbr-trpG module for catalyzing o-aminobenzoic acid generation, a salABCD gene cluster responsible for hydroxylating o-aminobenzoic acid into 5-hydroxy o-aminobenzoic acid, and a salABCD gene cluster responsible for hydroxylating 5-hydroxy o-aminobenzoic acid into 5-hydroxy o-aminobenzoic acid. And a trpDCBA module for converting the intermediate into the final product 5-HTP. The modules are respectively integrated into a plurality of non-essential gene regions, so that stable genetic expression is realized, and a complete metabolic pathway can be operated without plasmids or inducers. The strain can continuously accumulate 5-hydroxytryptophan (5-HTP) under a glucose fermentation condition, and has the advantages of simplicity and convenience in construction, high hereditary stability, low production cost, suitability for industrial-scale fermentation and the like.

The invention discloses a vector skeleton and a construction method thereof. The invention also discloses a test plasmid and a construction method thereof. According to the invention, the autonomous replication and stable existence characteristics of the additional body and the efficient integration capability of the Piggybac transposition subsystem complement each other. The additional body provides more exogenous gene copies, the transposon system ensures that the copies can be accurately and efficiently integrated into a host genome, and the additional body and the transposon system have a synergistic effect, so that the success rate and the efficiency of exogenous gene integration are greatly improved, some limitations existing in a traditional gene integration method are overcome, and the method is suitable for large-scale popularization and application. The integration efficiency is low; the gene expression is unstable, and the like. The mutation efficiency is high and can reach 65% at most, and the mutation frequency is stable.

The invention belongs to the technical field of molecular biology, and particularly relates to a metagenome sequencing data analysis method of a sample, electronic equipment and a system. The metagenome sequencing data analysis method comprises the following steps: acquiring sequencing data of a sample; comparing the sequencing data with a host reference genome, and splitting to obtain host genome data and microbiome data; and respectively analyzing the host genome data and the microbiome data. The invention aims to realize that data information of double omics, including microbiome data information and human genome data information, can be simultaneously obtained through one-time sampling from an analysis technology level. In addition, according to the analysis method, a reference gene set iHSMGC for human skin microbiome is integrated in a functional gene annotation analysis module suitable for microorganisms, and accurate annotation of skin microorganism habitat specific functional genes can be achieved.

The invention provides a multi-primer designed AAV vector ITR sequence integrity determination method, and belongs to the technical field of next-generation sequencing data analysis and application, and the method comprises the following steps: designing an AAV vector infection host cell with n primers in an ITR region, extracting intracellular fluid, and carrying out next-generation sequencing to obtain a primary Fastq file; the method comprises the following steps: carrying out coarse classification on sequences according to primer information, screening by using a biological information method to obtain a chimeric sequence, aligning one part of the chimeric sequence to a host genome, aligning the other part of the chimeric sequence to an AAV vector genome, and determining the junction of two sequences with different sources in the chimeric sequence as an ITR breakpoint; according to the samples, the primers and the sequence information corresponding to the ITR breakpoints, the distribution condition of the ITR breakpoints in the ITR area is counted, and a statistical table is obtained; and a qualitative and quantitative result of the ITR fracture position is obtained. According to the method, the integrity of the ITR region of the AAV vector sequence can be accurately qualitative and quantitative.

Methods and compositions for modulating a target genome are disclosed. This disclosure relates to novel compositions, systems and methods for altering a genome at one or more locations in a host cell, tissue or subject, in vivo or in vitro. In particular, the invention features compositions, systems and methods for inserting, altering, or deleting sequences of interest in a host genome.

The invention relates to a method of treating a disease or disorder in a patient in need thereof that includes providing an active pharmaceutical ingredient (API) to the patient by administering more than one split-dose of the API over a pre-determined period of time. In embodiments of the invention, the API is an mRNA encoding an antigen. The attractiveness of mRNA as a vaccine modality is supported by several advantages. As a non-infectious agent that does not require incorporation into the host's genome to confer activity along with its well-defined chemical composition, mRNA is regarded as a relatively safe vaccine modality.

The application discloses a DNA polymerase III mutant and application thereof. The mutant contains an amino acid sequence shown in SEQ ID No. 1, and the mutant can be applied to improving the mutation frequency of a host strain genome. In the application, the Escherichia coli is used as a starting strain, a high-efficiency evolution auxiliary plasmid is introduced, and the mutation frequency of the host is improved; combined with competitive pressure directional screening of a tryptophan structural analog 5MT, finally, the Escherichia coli engineering strain with high yield of tryptophan is obtained. The auxiliary plasmid comprises a pBad24 plasmid vector skeleton and an engineered Escherichia coli DNA polymerase III danQ nucleotide fragment. The high-efficiency evolution auxiliary plasmid provided by the application can significantly improve the mutation rate of the host genome, combined with the directional screening of 5MT, the traditional mutagenesis cycle can be greatly shortened, the engineering strain with high yield of tryptophan can be efficiently screened, and the application has important application value.

The invention discloses a differential diagnosis and prognosis evaluation method for a pleural effusion microbiome based on metagenome sequencing and application, belongs to the technical field of bioinformatics, and discloses a method for analyzing the microbiome of a pleural effusion sample, and the method comprises the following steps: carrying out metagenome next-generation sequencing on an in-vitro pleural effusion sample to obtain a sequencing reading; performing bioinformatics analysis on the sequencing reading, and determining microorganism composition information of the pleural effusion sample based on a verification result; by establishing a unified mNGS experimental process and a parallel bioinformatics analysis path, two kinds of technical information of different dimensions, namely microbiome structural characteristics and host genome copy number variation (CNV), are synchronously output from single sequencing data, and the defect that microbiological analysis and genome analysis need to be carried out in batches in the prior art is overcome.

Methods and compositions for modulating a target genome are disclosed. This disclosure relates to novel compositions, systems and methods for altering a genome at one or more locations in a host cell, tissue or subject, in vivo or in vitro. In particular, the invention features compositions, systems and methods for inserting, altering, or deleting sequences of interest in a host genome.

The application discloses a biological information-based genetic data mining system for Astragalus sinicus breeding, and particularly relates to the technical field of data mining; the system is characterized in that: raw sequencing data of a host genome of Astragalus sinicus and a symbiotic microorganism genome of rhizobium is collected and synchronized to generate a standardized genetic information dataset; sequence cross-contamination sites between the host genome and the symbiotic microorganism genome are identified, and genetic information interference from the microorganism is removed to obtain purified host genome data free of microorganism interference; the contribution of the microorganism genome to target traits of Astragalus sinicus is analyzed to obtain a microorganism effect weight; the purified host genome data and the microorganism effect weight are integrated to construct a trait association analysis model of Astragalus sinicus and locate trait association sites; finally, candidate breeding markers are screened based on the trait association site information to obtain a precise breeding genetic marker set; the application improves the accuracy and efficiency of Astragalus sinicus breeding.

An oral vaccine for Hepatitis B is disclosed. The oral vaccine for Hepatitis B includes a delivery platform including Arthrospira platensis with a plurality of host genomes and a plurality of Hepatitis B surface antigen delivery vectors coupled to the plurality of host genomes. Each Hepatitis B surface antigen delivery vector of the plurality of Hepatitis B surface antigen delivery vectors has a nucleotide sequence identical to nucleotide sequence of SEQ ID NO. 2. Each respective Hepatitis B surface antigen delivery vector of the plurality of Hepatitis B surface antigen delivery vectors includes at least one surface antigen of Hepatitis B with a weight ratio of the delivery platform to the at least one surface antigen of Hepatitis B in a range of 1: 10-4 to 1: 2x10- 3 (delivery platform: at least one surface antigen of Hepatitis B).

The invention discloses a targeted sequencing method for helicobacter pylori multi-site drug-resistant gene mutation detection, and relates to the technical field, and the targeted sequencing method comprises the following steps: obtaining a clinical gastric mucosa sample, extracting and purifying mixed DNA of genome DNA containing helicobacter pylori 23S rRNA, gyrA and pbp1 drug-resistant genes and host genome DNA, and introducing a competitive internal standard into the purified mixed DNA; taking the competitive internal standard and the mixed DNA as templates, and carrying out a first round of multiple PCR amplification by virtue of a composite primer system, so as to obtain a first amplification product; purifying the first amplification product, carrying out solution hybridization capture by using a probe library, and washing by using a washing solution at a specific temperature to obtain an enriched product; taking the captured enriched product as a template, carrying out a second round of PCR amplification by using a primer carrying a complete sequencing joint, and constructing a sequencing library; according to the invention, high-accuracy synchronous detection and complex sample applicability of the helicobacter pylori multi-site drug-resistant gene can be effectively realized.

The invention discloses a DNA polymerase III mutant and application thereof. The mutant comprises an amino acid sequence as shown in SEQ ID No.1. The mutant can be applied to improvement of host bacterium genome mutation frequency. Escherichia coli is taken as a starting strain, and efficient evolution helper plasmids are introduced, so that the host mutation frequency is improved; and combining with the tryptophan structural analogue 5MT competitive pressure directional screening to finally obtain the escherichia coli engineering strain with high tryptophan yield. The helper plasmid comprises a pBad24 plasmid vector skeleton and an engineered escherichia coli DNA polymerase III danQ nucleotide fragment. The high-efficiency evolution helper plasmid provided by the invention can significantly improve the mutation rate of a host genome, can greatly shorten the traditional mutagenesis period by combining with 5MT directional screening, can efficiently screen high-yield tryptophan engineering strains, and has important application value.

According to some embodiments herein, methods and kits for labeling and analyzing nucleic acids are provided. In some embodiments, sequence-specific labeling is performed on polynucleotide sequences associated with a host genome, and the presence or absence of patterns characteristic of extragenomic sequences are determined.