400 results about "Epigenetic Profile" patented technology

Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity of RNA-programmable endonucleases, such as Cas9, or for controlling the activity of proteins comprising a Cas9 variant fused to a functional effector domain, such as a nuclease, nickase, recombinase, deaminase, transcriptional activator, transcriptional repressor, or epigenetic modifying domain. For example, the inventive proteins provided comprise a ligand-dependent intein, the presence of which inhibits one or more activities of the protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding of a ligand to the intein results in self-excision of the intein, restoring the activity of the protein.

The invention provides a method for constructing a rice epigenetic recombinant inbred line, and belongs to the technical field of molecular biology and genetic breeding. According to the method for constructing the rice epigenetic recombination inbred line, a fertile rice DDM1 gene function weakening mutant is obtained through a CRISPR / Cas9 gene editing technology and hybridized with wild type rice with the same background to obtain F1, then the F1 and the wild type rice are subjected to backcrossing to obtain BC1F1, single-plant offspring selfing with the DDM1 genotype being the wild type is selected, selfing is conducted for multiple generations through a single-grain transmission method, and the rice epigenetic recombination inbred line is obtained. According to the present invention, the strain population with stable inheritance is constructed, such that the rice epigenetic recombinant inbred line is obtained, and has characteristics of rich phenotype, genetic and epigenetic variation so as to provide important population resources for batch identification and the like of important agronomic shape functional sites of rice.

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 relates to the technical field of gene sequencing, in particular to a silkworm gene sequencing path optimization system and method based on a hybrid parallel genetic algorithm. According to the technical scheme, the method comprises the steps of data preprocessing and feature modeling, hybrid parallel genetic algorithm optimization, dynamic path planning and resource allocation and multi-omics verification and result output. Reference is provided for assembling path planning by recognizing the repeated area, local optimum is avoided by means of the hybrid parallel genetic algorithm, efficient assembling of the high-complexity repeated area is achieved, standardization processing is carried out on data, errors caused by data differences are reduced, and the accuracy of assembling path planning is improved. The multi-omics feedback correction module integrates transcriptome and epigenetic data, corrects an assembly result and inhibits error accumulation, and meanwhile, based on deep Q network model reinforcement learning and a dynamic resource scheduling module, assembly strategies and resource allocation are dynamically adjusted, efficient utilization of computing resources is achieved, and resource waste is reduced.

An epigenetic regulatory factor ZmULT1 related to corn grain size regulation and heat stress response and the use thereof, which solve the technical problems of how to increase the grain size and / or heat resistance and / or lodging resistance of corn. Use of a substance for reducing the content of the protein ZmULT1 or a substance for inhibiting the expression of the encoding gene of the protein ZmULT1, which use is any one of the following: P1, the use in increasing the grain size of corn; P2, the use in improving the heat resistance of corn; P3, the use in increasing the lodging resistance of corn; and P4, the use in plant breeding. The homozygous mutant strain with knockout of the ZmULT1 gene has a reduced plant height and an increased grain size, and exhibits significant heat stress resistance, this indicates that the research on the gene can further enrich the use of epigenetics in crops and is of important significance for improving the grain size, heat resistance and lodging resistance of corn.

The invention discloses a single-cell multi-modal data integration method based on an attention mechanism and a graph variation auto-encoder. The method comprises the following steps: step 1, pre-processing multi-modal data and constructing a cell relation graph; step 2, cross-modal adjacency matrix fusion based on multi-head attention; step 3, performing graph variation auto-encoder training and multi-objective optimization; 4, performing multi-target loss calculation and model joint optimization; and 5, carrying out low-dimensional embedding extraction and clustering analysis on the cells. According to the method, single-cell transcriptome and epigenetic group data are fused through a multi-head attention mechanism, and low-dimensional embedding representation of cells is learned by using a graph variation auto-encoder, so that efficient integration and clustering analysis of single-cell multi-modal data are realized.

The technology disclosed relates to detecting gene conservation and expression preservation. In particular, the technology disclosed relates to detecting gene conservation and epigenetic signals for a reference genetic sequence in comparison to a variant of the reference genetic sequence at base resolution through the generation of a plurality of alternative representations of the sequence in chromatin form which may represent evolutionary conservation, transcription initiation, or epigenetic signals, mapping the plurality of alternative chromatin sequences to a gene expression alterability classifier to generate a gene expression class prediction for the variant, and mapping the alternative chromatin sequence to a pathogenicity predictor to detect pathogenicity of variants.

The invention relates to the fields of epigenetic regulation and tumor treatment, and aims to evaluate that the cell distribution of the mutant is consistent with that of H3 by constructing Bas-2B (H3K9R) and Bas-2B (H3K18R) stably transfected cell strains and analyzing the cell positioning condition of the H3K9R / H3K18R mutant through an immunofluorescence technique. According to the present invention, a Western blotting technology is adopted to detect the H3K9 / H3K18 lactic acid modification level of Bas-2B (H3K9R) and Bas-2B (H3K18R) cells compared to control cells so as to verify the influence of the H3K9R / H3K18R mutant on the H3K9 / H3K18 lactic acid modification; after Bas-2B (H3K9R), Bas-2B (H3K18R) cells and control cells of the Bas-2B (H3K9R) and the Bas-2B (H3K18R) cells are subjected to nickel compound exposure treatment, the influence of the H3K9R / H3K18R mutant on the nickel compound induced lung cancer is evaluated through a soft agar cloning formation experiment. An AGS cell line stably transfecting H2BK16R is constructed, and the cell localization condition of the H2BK16R mutant is analyzed through an immunofluorescence technology. According to the present invention, a Westernbloting technology is adopted to detect the lactic acid modification level of AGS (H2BK16R) cells so as to verify the influence of the H2BK16R mutant on the H2BK16 lactic acid modification; the influence of the H2BK16R on the malignant proliferation ability of the gastric cancer is researched through a soft agar clone formation experiment.

Provided is a gene ZmFIE2 for regulating maize kernel development, an encoded protein thereof, an InDel molecular marker, and a use thereof, aiming to solve the current technical problems of low maize haploid induction rate, long breeding cycle, and low maize yield. An InDel molecular marker for detecting ZmFIE2 mutants was screened out, and a primer for InDel molecular marker was designed, the InDel molecular marker and the primer thereof can be applied to the breeding of maize kernel size varieties and maize haploid or diploid lines. From the epigenetic level, it was found that ZmFIE2 regulates the development of maize embryo and endosperm, affects the accumulation of kernel storage materials, and affects the cell cycle process of endosperm cells, which has great value in improving maize yield. By using multiple created ZmFIE2 allele mutants, research has found that the loss of ZmFIE2 function can directly determine the division of endosperm cells and apomixis, which will provide new gene resources and new ways to achieve high-frequency haploid induction and heterosis fixation in maize.

The invention belongs to the technical field of biological analysis and evaluation, and particularly relates to a stem cell differentiation process multi-modal image fusion and intelligent evaluation method, which comprises a stem cell differentiation process multi-modal image fusion method: on the basis of constructing a multi-modal near-physiological mechanics microenvironment, carrying out image analysis by adopting the multi-modal image fusion method; an intelligent evaluation method for the stem cell differentiation process: developing an intelligent evaluation method based on deep learning driving on the basis of constructing a multi-modal near-physiological mechanical microenvironment, and revealing a mechanical-epigenetic regulation mechanism; the synergistic application of the two solves the core observation and regulation problems in stem cell differentiation research, and provides an industrialized intelligent platform for regenerative medicine. According to the method, the data integrity can be improved, the resolution limitation is broken through, the experiment process is accelerated, accurate mechanism analysis can be realized, automatic decision making is promoted, and the research and development cost is reduced.

Methods of predicting a chromatin state metric associated with a genomic region in a sample are provided. The methods comprise: receiving sequence data comprising genetic data and epigenetic data indicative of the presence of one or more epigenetic bases including methylated cytosine and hydroxymethylated cytosine at one or more genomic positions, the one or more epigenetic bases, the genetic data and epigenetic data obtained from a single assay; and predicting for each base or set of bases of the genomic region and using the sequence data associated with the genomic region, a value of the chromatin state metric, wherein the predicting is performed using a machine learning model.

The invention belongs to the technical field of biological detection, and particularly relates to a bisulfite-free detection kit for specific site 5-methylcytosine and a detection method thereof. According to the method, a TAPbeta treatment method is adopted, 5hmC is sealed through beta-GT, 5mC oxidation is carried out through TET, and 5mC is reduced into dihydrouracil (DHU) through pyridine borane, so that the apparent difference between 5mC and C and 5hmC is converted into single nucleotide polymorphism difference. In addition, a flow microsphere technology based on PNA-assisted click chemical connection starting is established to detect DNA methylation specific sites. A PNA clip is innovatively introduced into click chemical connection, and non-specific connection is inhibited. Target sequence enrichment, signal amplification and signal acquisition are carried out through surface-functionalized magnetic nanoparticles, and the detection sensitivity is improved to fM. The invention provides a new tool for high-specificity and high-sensitivity epigenetic marker detection.

This invention provides a method for hypertension risk assessment, relating to the field of epigenetic detection technology. It includes: performing event alignment and residual modeling on a qualified signal set to establish a base probability at the locus level and forming baseline features through neighborhood consistency screening; constructing a tunneling sensitization model and contextual attention, fusing discriminative and generative evidence to obtain enhanced features; quantifying IGF2BP3 and aligning and fusing it with the enhanced features; constructing an IGF2BP3-mediated metabolic network based on this, performing time-series modeling and stability assessment, and extracting final-state features; fusing the final-state risk vector with multi-gene scores to complete adaptive grading and compliant report generation. This method is robust, interpretable, and easy to deploy.

The invention relates to the technical field of genes, in particular to preparation of a Trmt61a enzyme activity deleted zebrafish model, and the Trmt61a enzyme activity deleted zebrafish model is used for preparing a zebrafish strain which stably inherits trmt61aD181A-P2A-EGFP knock-in zebrafish strain. According to the invention, trmt61a D181A mutation site specificity is introduced into a zebra fish genome by using a CRISPR / Cas9 technology, and a zebra fish model with Trmt61a catalytic activity deficiency and tRNA m1A modification level significantly reduced is obtained. The zebrafish model fills the existing research blank, provides an available in-vivo research model for biological development regulation mechanism research related to tRNA m1A epigenetic modification and pathological mechanism analysis of diseases (such as malignant tumors and hematopoietic dysfunction), and can be directly used for exploring the core effect of the epigenetic modification in development and diseases.

This invention belongs to the field of plant genetic engineering technology, specifically relating to the application of H3K27me3 in regulating the cotton response to potassium chloride stress. By integrating CUT & Tag chromatin analysis and RNA-seq, this invention demonstrates that potassium chloride stress induces a reduction in H3K27me3 deposition across the entire genome, accompanied by characteristic stress phenotypes in cotton seedlings. Inhibition of H3K27me3 using RDS 3434 significantly improved KCl-induced physiological damage, confirming the functional correlation between this epigenetic marker and stress tolerance. Furthermore, virus-induced gene silencing confirmed that genes associated with H3K27me3 are important components of the cotton ion stress response network. Therefore, this invention elucidates the epigenetic landscape regulating adaptation to potassium chloride stress.

Microglial spatial heterogeneity remains a crucial yet poorly studied question in light of potential cell-directed therapies for Alzheimer`s disease (AD). Little is known about the dynamics of spatially distinct microglia states, which are either adjacent or non-associated with the plaque site, and their selective contributions to neurodegeneration in vivo. So far, research has essentially focused on pathology-associated microglia. Here, we combined novel multicolor fluorescence fate mapping, single-cell transcriptional analysis, epigenetic profiling, advanced immunohistochemistry and computational modelling to comprehensively characterize the relation of plaque-associated and non-plaque- associated microglia during neurodegeneration. This approach enabled us to identify and characterize non-plaque-associated microglia as a unique and highly dynamic microglial state in a mouse model of AD. Non-plaque-associated microglia modulate network expansion, quickly adapt to environmental cues and their transition to plaque-associated microglia can be specifically modulated during disease, contrary to their reputation as a passive bystander subpopulation. This description of the dynamics of spatially segregated microglial states and their distinct molecular features may therefore open promising new avenues for state-specific therapeutic interventions during neurodegeneration.

The invention provides a method for the analysis of a biological sample to determine multiple types of information therefrom in a streamlined, combined workflow, where all information is obtained in a sequencing-based analysis. The information includes the presence and concentration of specific plasma proteins in a blood sample: the number, location, and types of histone modifications associated with cell-free DNA obtained from the same sample: the sequence of cfRNA and cfDNA in the cell-free DNA sample; and epigenetic information pertaining to the cell-free DNA, such as hydroxy methylation and methylation profiles, i.e., the distribution of 5-hydroxymethylcytosine (5hmC) and 5-methylcy tosine (5mC) residues, respectively. The invention additionally pertains to a classical sequencing-based method for analyzing a biological sample to determine one or more non-classical sequence features of the sample. Compositions, kits, and related methods are also provided, including an embodiment in which truncated sequencing adapters are used in conjunction with barcoded PCR primers.

The present disclosure is directed to compositions and methods for increasing expression of target genes in a cell, e.g., using an expression activator that comprises a targeting moiety that binds a target gene and an effector domain comprising an epigenetic activating domain. Systems comprising two or more expression activators are also disclosed.

The invention includes improved methods and compositions for reduction of a C5-C6 double bond of a cytosine. In particular, the improved methods and compositions for reduction of a C5-C6 double bond of a cytosine is via enzymatic means, not via chemical means. In particular, the disclosure is directed to methods of converting 5,6-dihydro-fC (fC) and / or 5,6-dihydro-caC to 5,6-dihydro-U (DHU). In particular, the disclosure is directed to methods of converting 5fC and / or 5caC to DHU. In addition, the disclosure is directed to methods for detection of epigenetic cytosine modification, particularly cytosine methylation, using ene reductases to reduce the C5-C6 double bond of cytosine.

The invention belongs to the technical field of biology, and particularly relates to a construction method of epigenome edited zebrafish, sgRNA of a targeted zebrafish runx2b gene promoter region and application of the sgRNA. The invention provides a construction method of epigenome edited zebrafish, which comprises the step of carrying out methylation editing by using a CRISPR / dCas9-methyltransferase system targeting runx2b gene promoter region, thereby inhibiting runx2b gene expression and reducing intermuscular bone formation. According to the method, the expression level of the runx2b gene is accurately regulated and controlled through an epigenetic editing technology on the premise that a DNA sequence is not changed, and formation of fish intermuscular bones is effectively reduced. The zebra fish F0 treated by the method represents that the runx2b mRNA expression level is obviously reduced, and the intermuscular bones of the eleventh to sixteenth sarcomedo regions of adult F0 generation fish are obviously shorter than those of a control group, and the shortening range reaches 23.3% to 38.8%. Besides, the method provides theoretical basis and technical support for improving fish economic traits by accurately regulating and controlling the expression mode of the key economic trait gene and simultaneously keeping the integrity of genome DNA (Deoxyribose Nucleic Acid).

The present invention relates generally to compositions, systems and methods for modulating hepatitis B virus (HBV) by targeting gene repression. In particular, the present invention provides an epigenetically modified DNA targeting system, such as a CRISPR-Cas / guide RNA (gRNA) system, for transcriptional repression of hepatitis B virus genes to promote cell phenotypes that lead to reduced HBV infection. In some embodiments, the epigenetically modified DNA targeting systems of the present invention bind to or target a target site of at least one gene in the hepatitis B virus DNA sequence or a regulatory element thereof in a cell. In some aspects, the systems provided herein relate to transcriptional repression of one or more hepatitis B virus genes and / or regulatory elements thereof. In some aspects, the invention also provides methods and uses associated with the provided compositions, such as in repression of hepatitis B virus replication and expression associated with hepatitis B infection.

The invention discloses a recombinant genetically engineered bacterium for producing a micafungin precursor FR901379 and an application of the recombinant genetically engineered bacterium. The recombinant genetically engineered bacterium for producing the micafungin precursor FR901379 is obtained by performing overexpression on an epigenetic modification factor in a phomopsis sheathing genome and performing screening to obtain the recombinant genetically engineered bacterium for producing the micafungin precursor FR901379. The epigenetic modification factor comprises a histone methyltransferase (Dot 1), a histone methyltransferase (Set2) or a histone deacetylase (Rpd3). The yield of FR901379 produced by the engineering strain is increased by 40% compared with that of an original strain. The method disclosed by the invention has the characteristics of simplicity and convenience in operation, high transformation efficiency and good genetic stability.

An engineered transcriptional modulator (ETM) comprising: (a) at least one epigenetic effector domain; operably linked to (b) an endonuclease.

The invention provides application of GW5 gene promoter methylation based on a multi-omics gene mining technology in regulation and control of rice grain length, and relates to the technical field of biology. On the basis of a generic genome micro-core germplasm population, multi-dimensional omics data such as a genome and an epigenome are integrated, a rice epigenome map is constructed, a stable methylation polymorphism marker in the map is utilized, a rice grain width phenotype is combined to carry out multi-omics association analysis, a new epigenetic allele of the GW5 gene is successfully mined, and the GW5 gene is successfully identified. It is found that the upstream promoter region of the GW5 gene has two epigenetic states of hypermethylation and hypomethylation in different rice germplasm backgrounds, and after demethylation editing is carried out on the region, the phenotype that the grain length is remarkably increased is shown. Therefore, detection of the rice grain length character can be realized according to the promoter methylation level of the GW5 gene, and regulation and control of the rice grain length character can be realized by regulating and controlling the promoter methylation level of the GW5 gene.

The invention discloses application of a CsDDM1 gene in regulating and controlling the length of cucumber fruits, and relates to the technical field of bioengineering breeding. The nucleotide sequence of the CsDDM1 gene is as shown in SEQ ID NO: 1. The CsDDM1 gene participating in cucumber fruit length regulation and control is identified and verified, then a cucumber CsDDM1 gene knockout material is constructed by utilizing a transgenic technology, and function research shows that the cucumber fruit becomes shorter by knocking out the CsDDM1 gene, so that the mechanism blank of epigenetic regulation and control of the character is filled, the commodity and ornamental value of the cucumber are increased, and the cucumber CsDDM1 gene knockout material has good application prospects. The method solves the problems that traditional breeding is long in period and short fruit germplasm is deficient, breeding efficiency is improved, germplasm resources are enriched, the research result also provides a new thought for character improvement of other crops, and scientific and technological progress and innovative development of the whole field are promoted.

The invention relates to application of WDR74 and / or ALYREF as molecular targets in esophageal squamous cell carcinoma diagnosis and treatment, and belongs to the technical field of biological medicine. Aiming at the problem that the esophageal squamous cell carcinoma lacks an effective targeted treatment means, the invention discovers that the expression quantity of WDR74 in tumor tissues is obviously higher than that in para-carcinoma tissues, and the high expression of WDR74 prompts poor prognosis of a patient, and reveals that WDR74 protein and ALYREF protein have specific binding, and the mRNA stability of EGFR is enhanced through ALYREF-mediated m5C RNA epigenetic modification, so that STAT3 phosphorylation is activated, and the treatment effect of the esophageal squamous cell carcinoma is enhanced. Further, the STAT3 is combined with the promoter region of the apoptosis-inhibiting gene MCL1, and finally cell apoptosis is inhibited and tumor formation is promoted. The invention provides a new molecular target and a solution for developing a WDR74 and ALYREF targeting medicine for treating esophageal squamous cell carcinoma and related diagnosis and prognosis evaluation products.

The invention discloses a sperm genome methylation detection method for safety evaluation of biological breeding crops by using primates and application, and relates to the technical field of safety evaluation of crops, the sperm genome methylation detection method comprises the following steps: dividing non-human primates into three groups, collecting sperms after long-term feeding, and extracting DNA (Deoxyribose Nucleic Acid); carrying out whole genome sequencing and quality control after bisulfite treatment; the epigenetic safety of crops is comprehensively evaluated by analyzing the methylation level of a whole genome and a functional region and functional enrichment of a differential methylation region and related genes thereof; according to the sperm genome methylation detection method for evaluating the safety of the biologically bred crops by utilizing the primates and the application, by utilizing a high-resolution WGBS technology, subtle epigenetic changes which are difficult to find by traditional toxicology can be detected, and the sperm genome methylation detection method has important significance in cross-generation reproduction effect evaluation, and has a wide application prospect. A food safety evaluation system can be perfected, and a more scientific and reliable safety interpretation basis can be established.

Disclosed are bifunctional compounds (degraders) comprising a [Targeting ligand]-[Linker]-[Degron] adduct, the targeting ligand comprising a substituted pyridine compound, the bifunctional compounds targeting the epigenetic writer protein deoxyribonucleic acid methyltransferase 1, which is responsible for the maintenance of DNA methylation during cell proliferation, for degradation. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds to treat diseases and disorders characterized or mediated by aberrant DNMT1 activity.