241 results about "Base pair" patented technology

The invention provides a protein expression prediction method based on a convolutional neural network and a residual attention mechanism, and belongs to the field of bioinformatics and artificial intelligence. The method comprises the following steps: performing data cleaning and binary one-hot coding on a DNA sequence, inputting the coded DNA sequence into a feature extraction layer, and extracting local features of DNA; local features are extracted through a convolutional neural network, global features are obtained through a multi-head attention mechanism, and residual connection is combined; and finally, inputting the global features into a full connection layer to generate a protein expression prediction result. Furthermore, an SHAP interpretability method is utilized to interpret the output result of the prediction model, and the contribution of the basic group at each position in the DNA sequence to the predicted value is quantified. According to the method, deep learning and interpretability technologies are combined, the precision and credibility of protein expression prediction are remarkably improved, and the method is suitable for predicting protein expression.

The invention relates to the technical field of biological information, and provides a thermodynamic parameter-based dsRNA / siRNA target sequence design method, which comprises the following steps of: standardizing coding sequences of candidate genes; presetting a reading frame, and segmenting the coding sequence of the candidate gene through translation of the reading frame to obtain a plurality of candidate dsRNA / siRNA target sequences; the candidate dsRNA / siRNA target sequences are read and analyzed, and base pairs of all the candidate dsRNA / siRNA target sequences are obtained; presetting thermodynamic parameters of all the base pairs, calculating the sum of the thermodynamic parameters of all the base pairs, and obtaining final thermodynamic parameters of the candidate target sequence in combination with the correction parameters; and calculating the score of each candidate dsRNA / siRNA target sequence according to the thermodynamic parameters, and determining the candidate dsRNA / siRNA target sequence with the highest score as the optimal dsRNA / siRNA target sequence.

The invention belongs to the technical field of biomedical engineering, and particularly relates to a single-base resolution laminated two-dimensional material nanopore structure, a DNA sequencing device and a DNA sequencing method. The two-dimensional material nanopore structure comprises an insulating layer and conducting layers arranged on the upper side and the lower side of the insulating layer, through nanopores are formed in the insulating layer and the conducting layers, and the pore diameter of the nanopores is 2-5 nm; the insulating layer and the conductive layer are made of two-dimensional materials. The conductive layers on the two sides serve as upper and lower electrodes, and a power supply is connected between the upper and lower electrodes to form a phase conductive path which is provided with a longitudinal current detection element. A plurality of groups of two-dimensional material nanopore structures are stacked, and meanwhile, a plurality of groups of base pair signals are obtained. According to the invention, the advantages of small thickness, high physical strength and the like of the two-dimensional material nanopore are kept by using a few layers of two-dimensional material films, the vibration of the films is reduced by increasing the number of layers and improving the mechanical strength, so that the signal-to-noise ratio is improved, and the spatial resolution of the nanopore sensor is improved by designing the upper electrode and the lower electrode.

A nucleic acid molecule comprising: i) a first nucleic acid comprising a double stranded inhibitory ribonucleic acid (RNA) molecule comprising a sense and an antisense strand designed with reference to a nucleotide sequence comprising a cardiovascular disease associated gene to be silenced and wherein said cardiovascular gene is proprotein convertase subtilisin kexin 9 (PCSK9) there is provided a single stranded deoxyribonucleic acid (DNA) molecule conjugated to the 5’ end of said sense strand; and ii) a second nucleic acid comprising a double stranded inhibitory ribonucleic acid (RNA) molecule comprising a sense and an antisense strand designed with reference to a different cardiovascular disease associated gene to be silenced wherein said cardiovascular gene is lipoprotein (a) (Lp(a)) and wherein there is provided a single stranded deoxyribonucleic acid (DNA) molecule conjugated to the 5’ end of said sense strand wherein the single stranded deoxyribonucleic acid (DNA) molecule is substantially complementary to the single stranded deoxyribonucleic acid (DNA) molecule set forth in i) above and anneals by complementary base pairing to form a double stranded DNA linker that links the first and second double stranded inhibitory ribonucleic acid (RNA) molecules.

The invention discloses a primer set determination method and device, which can be applied to the technical field of biological medicine, and comprises the following steps: calculating the dimer score of each pair of primers and constructing a dimer score matrix, screening out primer pairs with scores lower than a threshold value, and directly excluding primer combinations which are easy to form dimers. The Gibbs free energy matrix is used for further screening, the larger the absolute value of the Gibbs free energy is, the more stable the dimer is, and the primer pairs with overlarge absolute values of the free energy are eliminated through comparison with a threshold value. Finally, the Gibbs free energy is corrected through a loss function, a corrected free energy matrix is obtained, the corrected free energy is combined with the influence of non-standard base pairing, the probability of dimer formation is further accurately evaluated, and a better primer pair is screened out again. Through multiple rounds of strict screening, the formation probability of the primer dimer is reduced to the greatest extent, so that the occurrence of false positive results caused by the primer dimer is effectively reduced, and the occurrence probability of the false positive rate is further reduced.

A reference model DRFORMER for downstream tasks of an RNA sequence comprises the following steps: S1, constructing 24-dimensional image visual features based on structural features, distance features and base pairing features of the RNA sequence; s2, pre-training the visual features of the image by using a SWIN model, and generating a visual reference model SWIN-RNA (Ribonucleic Acid); s3, the visual reference model SWIN-RNA is combined with an RNA sequence model, multi-modal feature fusion is achieved through a self-attention module and a cross attention module, and then a multi-modal reference model DRFORMER is constructed and used for RNA downstream task analysis. According to the scheme, the analysis and prediction performance of the reference model for downstream tasks can be improved.

The invention discloses a CAR donor plasmid, a T cell as well as a preparation method and application of the CAR donor plasmid and the T cell, and belongs to the field of genetic engineering and immune cell therapy. An RNP compound and donor plasmid DNA are transferred into a T cell through electroporation, and a CAR expression unit is integrated into a T cell genome at a fixed point to prepare the CAR T cell. The donor plasmid DNA comprises a plasmid skeleton, a homologous arm sequence, an EF1 alpha core promoter, a CAR expression element and an SV40 poly A termination signal. The number of base pairs of the plasmid is 4544 bp, the toxicity of the plasmid to T cells after electroporation can be effectively reduced, and the T cell viability and the CAR integration efficiency are improved. Compared with dsDNA and ssDNA, the plasmid DNA is convenient to prepare and low in cost; therefore, the plasmid is taken as the donor template DNA, and the CRISPR / Cas9 technology is combined, so that the use of a virus vector can be avoided to improve the safety of the CAR T cell, and the production cost of the preparation of the CAR T cell can be effectively reduced.

The invention discloses a divalent nucleic acid aptamer fluorescence detection method based on an exonuclease I auxiliary target circulation strategy, and belongs to the field of analysis and detection.The divalent nucleic acid aptamer is a repetitive sequence composed of two monovalent nucleic acid aptamers and can form double-stranded DNA through base complementary pairing with complementary strand cDNA of the divalent nucleic acid aptamer, and the divalent nucleic acid aptamer can be used for fluorescence detection of the divalent nucleic acid aptamer. The method comprises the following steps: taking a bivalent nucleic acid aptamer as a template, forming a DNA silver nanocluster (DNA-AgNCs) under the action of silver nitrate and sodium borohydride, and when the target okadaic acid exists, combining the bivalent nucleic acid aptamer with the target, so that cDNA can be replaced from double-stranded DNA by the target. Exonuclease I is added to perform enzyme digestion on the cDNA and the divalent nucleic acid aptamer, so that the fluorescence intensity of the DNA-AgNCs can be rapidly reduced. The content of the okadaic acid can be judged by detecting the change of the fluorescence intensity. The invention provides a simple, convenient, rapid, high-sensitivity and high-specificity detection method for okadaic acid detection based on a divalent nucleic acid aptamer for the first time.

The invention provides a compound for releasing a urine fluorescent biomarker under induction of mitochondrial DNA mutation as well as a preparation method and application of the compound, and belongs to the technical field of medicines. The compound disclosed by the invention is prepared by the following steps: complementarily pairing a hybrid nucleic acid nano-carrier containing single-stranded DNA (Deoxyribose Nucleic Acid), an annular fluorescent reporter molecule and a Cas12a / crRNA compound through bases of DNA or RNA, and then coating polyethyleneimine and hyaluronic acid. A CRISPR / Cas12a system is selected as a converter of tumor specific mitochondrial DNA mutation information and urine fluorescence signals, a nano delivery system which responds to mtDNA single base mutation and is used for tumor progress monitoring and early metastasis warning is designed and synthesized, and the nano delivery system has a good application prospect in tumor progress monitoring and early metastasis sensitive detection.

The present application relates to the technical field of bioinformatics, and particularly relates to a method for constructing a biological age prediction model based on DNA methylation. The method comprises the following steps: obtaining whole genome methylation sequencing data of a human peripheral blood sample; classifying cell subpopulations of the human peripheral blood sample, and performing single-cell RNA sequencing processing on each cell subpopulation to obtain single-cell sequencing data including lymphocytes, neutrophils and monocytes; performing tissue-specific analysis on CpG sites within a range of 2000 base pairs upstream and downstream of each cell subpopulation-specific transcription factor binding site according to the single-cell sequencing data and the whole genome methylation sequencing data to obtain candidate marker site data. The present application can provide strong support for early detection of accelerated aging, prediction of related disease risks and guidance of precision medicine.

The invention relates to the technical field of DNA intercalating agents, in particular to a near-infrared luminous ruthenium (II) complex, a preparation method thereof and application of the complex as a DNA intercalating agent. The preparation method comprises the following steps: firstly, preparing a precursor 4 '-(1H-benzimidazole-2-yl)-2, 2': 6 ', 2' '-terpyridyl; then, preparing a target precursor, namely, 2-(4-(anthracene-10-yl)-6-(pyrazine-2-yl) pyridine-2-yl) pyrazine as a ligand; and finally, synthesizing a complex [Ru (An-di (2-Pz) Py) (Bitpy)]. The complex is inserted into a DNA base pair as an intercalating agent, has very strong interaction with DNA, and provides basic research for researching the interaction mode of the ruthenium (II) polypyridine complex of the tridentate ligand and DNA and taking the ruthenium (II) polypyridine complex as a diagnosis and treatment reagent.

The invention relates to a double-signal aptamer sensor and a preparation method and application thereof, and belongs to the technical field of sensors. The dual-signal aptamer sensor comprises a first compound, a second compound and a third compound, wherein the first compound comprises Au dimers and functionalized cDNA (complementary deoxyribonucleic acid) modified on the Au dimers; the first compound is Fe3O4 (at) SiO2-CDs, and the second compound is Fe3O4 (at) SiO2-CDs and an aptamer apt of aflatoxin B1, wherein the aptamer apt of aflatoxin B1 is modified on the Fe3O4 (at) SiO2-CDs; the Fe3O4 (at) SiO2-CDs comprise Fe3O4 (at) SiO2 and CDs which are modified on the Fe3O4 (at) SiO2; the first compound and the second compound are connected through complementary base pairing to form an assembly. Due to the introduction of the Raman signal probe, the Raman signal of the assembly is enhanced, meanwhile, the Au dimers have a quenching effect on the fluorescence of the magnetic substrate, and the fluorescence signal of the assembly is weakened. After the target is added, the aptamer is preferentially specifically combined with the target, the assembly is disassembled, the Au dimers fall off from the Fe3O4 (at) SiO2-CDs, and through magnetic separation, a Raman signal of precipitation is reduced along with the addition of the target, and a fluorescence signal is recovered. The dual-mode detection is realized by measuring the change of Raman and fluorescence signals of the precipitation part along with the target addition amount.

This invention discloses a G4-DNA tetrahedral probe electrode, its preparation method, applications, and application methods. This invention utilizes four DNA strands to self-assemble into a DNA tetrahedral structure based on Watson-Crick hybridization. The DNA tetrahedron and G4 strand can be connected to the electrode based on the interaction between thiol groups and the gold electrode, and complementary base pairing. The addition of the DNA tetrahedron, through the construction of a reasonable probe density, further improves the detection sensitivity. This invention utilizes square wave voltammetry for electrochemical detection of malachite green. The content of malachite green can be determined based on the strength of the current signal of its characteristic peak. Rapid detection of malachite green can be achieved in a short time, with a minimum detection concentration of 3.65 μg / kg, showing potential for on-site detection. Six repeated tests using this electrode yielded almost identical detection signals, indicating that the electrode has good reusability and stability.

To provide a chimeric ligase having improved discrimination ability to a mismatched base pair.SOLUTION: The present invention provides a chimeric ligase, wherein an OB-fold domain or an adenylation domain in a ligase derived from a thermophilic bacterium is substituted with a corresponding domain of a different species derived from a thermophilic bacterium, and the ability to discriminate a mismatched base pair is improved as compared with the ligase before substitution.SELECTED DRAWING: None

The invention provides a DNA frame confinement probe, a preparation method thereof and application of the DNA frame confinement probe in drawing micromolecular mercaptan fluctuation in endolysosome. The probe comprises a frame and a functional component, the functional component comprises a small molecule mercaptan response unit and a fluorescent unit, and the functional component is connected to the frame. The framework is of a regular tetrahedral structure and is formed by an S1-8th chain, an S2 chain, an S3 chain and an S4 chain through base complementary pairing and self-assembly. The small molecule thiol response unit is a fluorescent probe CyS2 and is coupled with the S1-8th chain through a copper-free click chemical reaction. The fluorescent unit is marked at the 3'end of the S2 chain by Alexa Fluor 488 fluorescent molecules. The DNA frame confinement probe is accurate and stable in targeting, outstanding in anti-interference capability, high in clinical applicability and high in detection specificity.

Methods and systems are provided that include measuring the size of a plurality of nucleic acid molecules using multiplex digital amplification reactions. In various embodiments, a digital amplification reaction uses multiple separate forward and reverse primer pairs to amplify targeted regions of the nucleic acid molecule, where the targeted regions are separated by a specified number of base pairs. In other embodiments, the digital amplification reaction uses a plurality of primer pairs that share a universal pair to amplify target regions that overlap each other. The methods and systems are particularly useful for determining the size distribution of nucleic acid molecules, or classifying the pathology of a subject from which nucleic acid molecules are sampled. Advantageously, the methods and systems can measure the size of long nucleic acid molecules without relying on inefficient amplification of very long amplicons.

The application discloses a kind of preparation and application of multi-target small nucleic acid drug based on small activation RNA technology, and is related to the field of biotechnology.The preparation method of the multi-target small nucleic acid drug includes the following steps: (1) selecting at least two anti-disease genes according to target disease;(2) intercepting the sequence of 1000 base pairs of the promoter region upstream of the coding region of the anti-disease gene;(3) according to the promoter sequence, avoid CpG island and locate the segment of species conservation, and cut a sequence containing 19 base length as a sense strand;(4) design an antisense strand according to the sense strand, and the 19 base of the antisense strand and the sense strand are completely complementary;(5) add two deoxythymine or uracil to the 3' end of each chain.The multi-target small nucleic acid drug has good therapeutic effect on heart failure, and has strong cancer cell killing ability and inhibition ability of cancer cell migration, and has wide application prospect.

Methods are provided for detecting gene deletions and driver mutations using tumor-specific methylation patterns from cell-free DNA and tissue biopsies. The methods exploit the mutual exclusivity between tumor-specific methylation and homozygous gene deletion, enabling detection through absence of expected methylation signals. Applications include detection of MTAP, PTEN, and RB1 deletions, as well as prediction of EGFR single nucleotide (SNV) and small (up to 50 base pair) insertions and deletions (indel) driver mutations, enabling identification of patients eligible for targeted therapies.

The present invention provides a method, device, medium and equipment for simulating virus mutation and infection based on quantum computing, which relates to the technical field of quantum computing. The method assigns quantum bits and rotation angles to each base pair of the virus and the host, and establishes a quantum circuit according to the required number of quantum bits; applies a Hadamard gate to the quantum bits to put the quantum bits in a superposition state; applies a U gate to the quantum bits in the superposition state to perform a characteristic comparison of the base pair rotation angles. If there are identical base pairs in the base pair sequences of the virus and the host, a CNOT gate is applied to the quantum bits representing the base pair; a measurement operation is applied to the quantum bits of the quantum circuit, and the infection probability is obtained by analyzing the count of the quantum bits with the state of 0 in the measurement results. Applying the present invention can simulate virus mutation and infection, and the simulation results are helpful for the treatment of virus-related diseases and the development of vaccines.

This invention relates to the interdisciplinary field of smart healthcare and digital twin technology, specifically to a dynamic medical twin system and interactive prediction method based on a physiological double helix driven and four-dimensional linkage modalities. The system continuously collects and fuses multi-source biophysical data through a physical entity helix, while a digital virtual helix solves a network of physiological equations coupled with metabolic and stress fields in real time. Both systems achieve endogenous synchronous mapping of gene loci and expressed proteins through a built-in base pairing engine. The four modalities of mirroring, deduction, intervention, and knowledge are responsible for high-fidelity real-time presentation, disease progression prediction, virtual intervention deduction, and clinical knowledge accumulation, respectively, forming a complete closed loop of "observation-deduction-intervention-learning." This invention elevates the system architecture from a static hierarchical stack to a dynamic life-body metaphor, supporting users to perform virtual operations on the twin and receive real-time feedback on multi-scale physiological responses across the entire system, achieving a leap from "morphological simulation" to "life mechanism simulation."

This invention provides a multivalent protein-targeting degradation system based on a programmable nucleic acid template, its preparation method, and its applications, belonging to the fields of biomedicine and molecular engineering. The system includes monovalent nucleic acid degradation units and a nucleic acid template. The monovalent degradation unit is formed by hybridization of two nucleic acid chains coupled with a target protein ligand and an E3 ubiquitin ligase ligand. The nucleic acid template has n loading sites, which assemble into multivalent nucleic acid degraders through complementary base pairing. This invention achieves precise control over the spacing and configuration of monovalent units by regulating the template spacer sequence length and topology, resulting in a spatially ordered multivalent synergistic degradation effect and significantly improving the degradation efficiency of target proteins. This system is highly modular and programmable, providing a new technological platform for the development of targeted protein degradation drugs.

Some embodiments relate to methods, systems, uses, or software for identification of structural variants (SVs) for regions of deoxynucleic acid (DNA) sequences. A device may receive, at a processor, a dataset comprising base pair data output from a sequencing by expansion process. A device may extract, at the processor, soft-clipped reads from the received dataset. A device may group, at the processor, the extracted soft-clipped reads based at least on their respective breakpoint. A device may determine, at the processor, a presence or an absence of a somatic structural variant by k-mer matching the grouped and extracted soft-clipped reads. A device may provide, at the processor, at least one determined somatic structural variant responsive to determining the presence of the somatic structural variant

Disclosed herein are the compositions and methods for solution-phase, phosphoramidite-free synthesis of nucleic acids, known as addamers. The addamers may be synthesized for any arbitrary sequence of DNA at any arbitrary length with a 3' base pair overhang in solution. Accordingly, disclosed herein are addamer reagents generated from bacterial plasmids as well as bacterially expressed, purified enzymes used to generate any given Nucleic Acid (NA) sequence in a process referred to as GreenSynth.

The invention relates to the technical field of biological medicines, and particularly provides a hair follicle regeneration nano activator as well as a preparation method and application thereof. The activator comprises a first coupling monomer and a second coupling monomer, an oligonucleotide sequence of the first coupling monomer and an oligonucleotide sequence of the second coupling monomer are at least partially complementary and form a double-chain structure through base pairing, the first coupling monomer is formed by coupling a first polypeptide and a first ssDNA, and the second coupling monomer is formed by coupling a second polypeptide and a second ssDNA. The second coupling monomer is formed by coupling a second polypeptide and a second ssDNA; wherein the first polypeptide and the second polypeptide are both specifically targeted to beta-catenin protein. The polypeptide-DNA-polypeptide dimer has a polypeptide-DNA-polypeptide sandwich-type dimer structure, can be specifically combined with beta-catenin in stem cells, only regulates and controls a Wnt / beta-catenin pathway, does not generate non-specific influence on other pathways, and can efficiently activate a hair follicle regeneration related signal pathway and promote a hair follicle development biological process.

The invention relates to the technical field of variety cultivation and identification in molecular biology, in particular to a molecular marker, a primer and a kit for identifying a rubber tree variety 'Yunnan research 621' and application of the molecular marker, the primer and the kit. The molecular marker is positioned on 66751525-66751724 basic groups of a No.10 chromosome, and the nucleotide sequence of the molecular marker is shown as SEQ ID No.1. The invention provides a molecular marker primer and a kit for a rubber tree variety 'Yunnan research 621', the technology can specifically identify and amplify a DNA sequence of the 'Yunnan research 621' variety, realizes accurate identification of the 'Yunnan research 621' variety, is helpful for improving the accuracy of variety identification, optimizes variety selection and regional suitability evaluation, and has the advantages of high specificity, high sensitivity, high sensitivity and the like. Therefore, a scientific basis is provided for planting and breeding of rubber trees, and healthy development of the rubber industry is promoted. The molecular marker, the primer pair or the kit can be used for distinguishing and identifying rubber tree varieties' Yunnan research 621 ', Yunnan research 651 and Yunnan research 98-305, and is simple and convenient to operate and suitable for large-scale application.

Disclosed herein are improved methods and compositions of de novo synthesis of nucleic acids by cyclic extension using nucleotides that have an N-linked or O-linked scar or protecting group, and subsequent removal of the scar or protecting group. During polymerase-nucleotide conjugate-based polynucleotide synthesis or after the synthesis is completed, nucleobases having a scar from linker cleavage can be converted back into native form by removal of the scars from the nucleobases. Secondary structure formation in the nascent chain, which may inhibit extension reactions, is suppressed by the use of monomers with protected nucleobases that prevent Watson-Crick base pairing and / or other structures. After the synthesis is completed, the nucleobases can be converted back into native form by palladium-based removal of the protecting groups.

The invention discloses an InDel molecular marker for detecting black spot resistance of broccoli, a method and application, and relates to the field of molecular biology. The site is located at 56724071bp-56724089bp of a broccoli chromosome 5, and the site has insertion / deletion variation of 18bp basic groups (the nucleotide sequence is as shown in SEQ ID NO. 1). When the site has a 18bp basic group (the sequence of an amplification product is shown as SEQ ID NO.2), the broccoli is a black spot resistant plant; otherwise, the plants are black spot sensitive plants. The invention also discloses a pair of specific primers for detecting the InDel molecular marker, and the nucleotide sequences of the specific primers are respectively shown as SEQ ID NO. 4 and SEQ ID NO. 5. The InDel molecular marker can rapidly and accurately detect the black spot resistance of broccoli germplasm resources at low cost, does not need field inoculation identification, can be used for early screening of broccoli black spot resistance varieties and molecular marker-assisted breeding, significantly improves the breeding efficiency, and shortens the breeding period.

The present invention is related to the field of gene editing. In particular, the gene editing is directed toward single nucleotide base editing. For example, such single nucleotide base editing results in a conversion of a OG base pair to a T*A base pair. The high accuracy and precision of the presently disclosed single nucleotide base gene editor is accomplished by an NmeCas9 nuclease that is fused to a nucleotide deaminase protein. The compact nature of the NmeCas9 coupled with a larger number of compatible protospacer adjacent motifs provide the Cas9 fusion constructs contemplated herein to have a gene editing window that can edit sites that are not targetable by other conventional SpyCas9 base editor platforms.