171 results about "Epigenetic Profile" patented technology

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.

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 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.

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

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.

The invention discloses a liver tissue regeneration regulation and control method based on epigenetic state regulation and control, and relates to the technical field of biology. Comprising the following steps: sampling the liver tissue at a plurality of preset time points after the liver tissue is damaged or partially resected, selecting a target gene related to liver tissue regeneration regulation, and detecting an epigenetic state of a promoter region of the target gene; comparing and analyzing the change of the epigenetic state of the target gene promoter region on the basis of detection results obtained at different time points, and determining epigenetic modification characteristics in the liver tissue regeneration process; according to an analysis result, intervening the expression level of a regulatory factor related to DNA methylation or DNA hydroxymethylation so as to regulate the epigenetic state of the target gene promoter region; after intervention is completed, the transcription expression condition of a target gene and the activity change of a cell signal channel related to liver tissue regeneration are detected, and the liver tissue regeneration process can be effectively regulated and controlled through the method.

The invention discloses a method and system for synchronously detecting host chromatin openness and in-vivo microbiome based on transposase, and belongs to the technical field of biological sequencing data analysis. According to the method, transposase is used for selectively fragmenting an open chromatin region of a host, and a microbial genome is almost randomly cut, so that synchronous enrichment of host and microbial DNA is realized; after high-throughput sequencing library construction and double-end sequencing, sequencing data is split into host source and non-host source reads through bioinformatics analysis, host chromatin state and microorganism composition are analyzed respectively, and a microorganism-host epigenetic regulation network is constructed; the invention further provides a matched DNA sequencing library and an analysis system, multi-scene research of infectious diseases, intestinal microecology, tumor microenvironment and the like is supported, a public database can be reanalyzed, and potential microbial interaction signals are mined. According to the method, the host-microorganism interaction research efficiency is remarkably improved, and a high-sensitivity and integrated technical scheme is provided for epigenetic regulation mechanism analysis.

The invention provides a synergistic treatment pharmaceutical composition for preventing and treating recurrence after hepatocellular carcinoma thermal ablation and application of the synergistic treatment pharmaceutical composition. Aiming at malignant tumor progression driven by ACSS3 gene silencing after thermal ablation, an epigenetic editing technology is innovatively combined with metabolite supplementation, and a preparation for specifically activating or promoting ACSS3 gene expression and sodium propionate are cooperatively used, so that ACSS3 can be remarkably reactivated or expression can be promoted in a xenograft model derived from a cell line and a patient; the compound can be used for recovering propionyl-coenzyme A synthesis and normal propionic acid metabolism and inhibiting fatty acid beta-oxidation, so that the growth and metastasis of post-ablation hepatocellular carcinoma (HCC) are effectively blocked, and the limitation of a single therapy is overcome. A clearer mechanism target is provided for preventing recurrence after HCC thermal ablation, meanwhile, the prepared targeting nano-liposome preparation has a synergistic effect, and as a brand-new treatment strategy, the defect that intervention on recurrence roots is insufficient in the prior art is overcome.

Provided are a multi-species epigenetic modification prediction method and apparatus. The method comprises: acquiring a genome sequence and a pre-established multi-species epigenetic modification prediction model, wherein the multi-species epigenetic modification prediction model comprises a feature extraction module and a multi-task learning model; performing feature extraction on the genome sequence on the basis of the feature extraction module to obtain a feature representation; and inputting the feature representation into the multi-task learning model for prediction to obtain modification level data of each epigenetic modification type. By combining the feature extraction module and the multi-task learning model, a cross-species prediction capability is achieved, and modification level data of multiple epigenetic modification types can be predicted more accurately. The present invention can be widely applied to fields such as plant epigenetics research, agricultural production, and biodiversity conservation.

The present invention relates to a new therapeutic approach for treatment of ANCA-associated vasculitis (Anti-neutrophil cytoplasmic autoantibody-associated vasculitis, AAV). It provides an agent for reducing expression of proteinase 3 (PR3) in a cell, in particular, a gene editing compound targeting the proteinase 3 gene, an epigenetic editing compound targeting the proteinase 3 gene, or an expression vector encoding an inhibitory oligonucleotide capable of selectively binding to a target nucleic acid sequence in mRNA encoding proteinase 3, e.g., an inhibitory oligonucleotide capable of inducing RNAi or an antisense oligonucleotide. Further, a method of reducing expression of proteinase 3 in a hematopoietic stem cell or cell derived therefrom, e.g., a neutrophil, is provided, as well as such cells having a reduced expression of proteinase 3. The cells or agents can be used for treating a subject having a proteinase 3-ANCA-associated vasculitis.

The invention discloses a lung nodule diagnosis method based on plasma DNA methylation characteristics and application, and the method comprises the following steps: S1, collecting peripheral blood of a subject in a special cfDNA preservation tube, carrying out centrifugal separation to obtain plasma, extracting cfDNA by adopting an optimized paramagnetic particle method or column extraction method, carrying out quality control on the cfDNA, then carrying out thorough hydrosulphite conversion treatment on the cfDNA, and carrying out purification treatment on the cfDNA to obtain the plasma; unmethylated cytosine is converted into uracil, and methylated cytosine is kept unchanged. The invention is derived from the selection of an early and stable epigenetic marker of DNA methylation, and replaces traditional dependent clinical parameters or mutation signals appearing at a late stage. According to the method, the problem of insufficient discrimination capability (AUClt; 0.60) caused by limited input information of an existing clinical prediction model (such as a MayoClinic model) is directly solved.

The present application relates to a kind of sgRNA targeting Plagl1 gene DMR, epigenetic editing system and its application.Specifically, the present application provides sgRNA targeting Plagl1 gene differential methylation region, which forms epigenetic editing system with dCas9-Tet1-CD fusion protein.The system is loaded in injectable type light-cured silk fibroin hydrogel, the expression of Plagl1 gene in periosteum stem / progenitor cells is accurately activated by targeted demethylation modification, thereby promoting osteogenic differentiation.The present application combines epigenetic regulation with biomaterial delivery, and provides a safe, efficient new strategy for jaw bone defect regeneration and repair.

The present application relates to the field of biomedicine, and provides an epigenetic editing tool for targeting a hepatitis B virus gene and a use thereof.

Analysis of cell free DNA (cfDNA) fragment ends in cancer patients provides a direct relationship between epigenetic alterations and cfDNA fragmentation for non-invasive disease detection and patient treatment. In certain embodiments, methods for cancer diagnosis and treatment include detecting methylation and expression differences in a patient that affect cell free (cfDNA) size and coverage. In certain aspects, include methods for determining circulating cfDNA fragmentation in a provided sample, including determining a genomic sequence to identify cfDNA endpoints; analyzing frequencies of cfDNA breaking points at a plurality of positions in the genome sequence; as a result, a circulating cfDNA fragmentation is determined.

The invention relates to an application of an ergothioneine preparation in preparation of a product for remodeling an inflammation-related DNA methylation spectrum and / or reducing epigenetic age, develops a new application of ergothioneine, and provides a research basis for wide application of ergothioneine. Meanwhile, a brand-new strategy for remodeling the inflammation-related DNA methylation spectrum and / or reducing the epigenetic age is also developed, and it is found that ergothioneine has very remarkable effects in the aspects of remodeling the inflammation-related DNA methylation spectrum and reducing the epigenetic age. Specifically, the methylation rate drift of immune regulation, inflammation and senescence related gene loci is effectively corrected, so that the epigenetic age and the inflammation age are effectively reduced.

The present invention relates to an in vitro method for predicting the chronological age of a test Chinese Hamster Ovary (CHO) cell or population of test CHO cells, the method comprising the steps of: (a) determining the test methylation level of a set of specific CpG sites from genomic material obtained from the test CHO cell or from the population of test CHO cells from a CHO cell line using a DNA-methylation bead-based array; (b) comparing the test methylation level determined from step (a) with a reference methylation level of the same set of specific CpG sites from an age-correlated reference sample, thereby establishing the epigenetic age and predicting the chronological age of the test CHO cell or the population of test CHO cells wherein the set of specific CpG sites comprises at least 10%, preferably 30%, more preferably 50% of the CpG sites indicated in Table 1.

The invention provides a group epigenetic analysis method and system based on consensus peak recognition, and belongs to the technical field of bioinformatics, and the method comprises the steps: S1, recognizing a consensus peak from a multi-sample peak file based on a position offset threshold and a minimum sample proportion; s2, calculating the coverage depth of a consensus peak based on the segment / read segment to obtain an original peak intensity matrix; s3, eliminating GC preference through GC content inter-partition local correction; s4, performing cross-sample normalization by adopting methods such as DESeq2, TMM and the like; and S5, automatically removing a hidden batch effect by utilizing potential variable analysis. The system correspondingly comprises five functional modules. According to the method, the problems of inconsistent peak coordinates, incomparable signals and large technical deviation interference in multi-sample epigenetic data are solved through an integrated process, full-automatic generation from original data to a high-quality and high-comparability peak intensity matrix is realized, and the analysis efficiency and accuracy of researches on large-scale groups ChIP-seq, ATAC-seq and the like are remarkably improved.

The application provides a Prime editing efficiency prediction method and system based on deep learning and epigenetic data fusion, which comprises the following steps: obtaining a target DNA sequence and performing data preprocessing on the target DNA sequence; performing multi-channel pseudo-image coding on the preprocessed target DNA sequence to obtain a pseudo-image representing the characteristics of the DNA sequence; inputting the pseudo-image into a trained Prime editing efficiency prediction model to obtain a prediction result, which comprises the following steps: inputting the pseudo-image into a multi-scale convolution module for feature extraction; adaptively weighting the extracted features through a channel attention and a convolution attention module; inputting the weighted features into a multi-branch fully connected network for prediction of effective editing, non-editing and error editing efficiency to obtain a prediction result. The method improves the Prime editing efficiency prediction accuracy and generalization ability.

The invention discloses a biological age assessment method and system based on full life cycle DNA methylation and application, and belongs to the technical field of bioinformatics. The method comprises the following steps: firstly, carrying out quality control and standardization treatment on obtained original DNA methylation data; then, screening differential methylation sites significantly related to calendar age as features; then, by taking calendar age as a target variable, constructing a regression model by adopting a LightGBM gradient lifting framework to obtain a methylated clock model; then, predicting the DNA methylation age of the individual by using the model, and calculating an epigenetic age acceleration value based on the deviation between the DNA methylation age and the calendar age; and finally, carrying out correlation analysis on the age acceleration value and health or physiological indexes of different life stages, so as to evaluate the biological aging state of the individual and predict related health risks. The method covers the whole life cycle, is suitable for Chinese population, and can provide an effective tool for clinical disease risk prediction, health management and anti-aging intervention effect evaluation.

The application discloses a double-drug self-enhanced layered double hydroxide nanosystem and application thereof. The iron-ruthenium layered double hydroxide in the nanosystem has double enzyme activity, can efficiently catalyze H2O2 to generate O2 and active oxygen in a tumor microenvironment, significantly relieves hypoxia while inducing oxidative stress, the MCT4 specific inhibitor VB124 in the system creates an acidic microenvironment by blocking lactic acid output, amplifies the catalytic efficiency of FeRu, and establishes a self-enhanced catalytic effect; and the co-loaded epigenetic regulator JQ1 down-regulates the expression of PD-L1 by inhibiting BET protein. The system amplifies the catalytic efficiency of FeRu, significantly induces ferroptosis, reverses the immunosuppressive microenvironment with the help of epigenetic regulation, induces the release of damage-associated molecular patterns, causes the infiltration of immune cells, and finally cooperatively triggers a strong anti-tumor immune response. The self-enhanced catalysis-epigenetic regulation synergistic strategy realized by the system provides an innovative solution for improving the effect of tumor immunotherapy.

Provided herein are methods and compositions for an epigenetic clock comprising differentiation-independent methylation sites to asses biological age of a human subject.

The invention discloses a DNA methylation regulatory gene identification method related to formation of cold resistance of Brassica campestris L. and application of the DNA methylation regulatory gene identification method. The method belongs to the technical field of winter rape cold resistance epigenetic regulation mechanism analysis. According to the invention, a methylation sensitive amplification polymorphism technology is utilized, four Chinese cabbage type winter rape materials with large cold resistance difference after the same variety is domesticated in different breeding environments are selected as research objects, the change rule of DNA methylation after treatment at 4 DEG C for 24 hours and recovery growth for 2 days is analyzed, and finally differential methylation gene expression is verified by utilizing a qPCR technology. The invention provides a reference method for DNA methylation research of plants under adversity stress, and compared with other epimics research such as DNA methylation, the method is simple and convenient to operate and low in cost, does not need high-throughput sequencing, and only needs one-generation sequencing. The candidate gene identified by the invention provides a genetic basis for explaining a cold resistance evolution molecular mechanism of Brassica campestris L. and guiding cold resistance improvement of northern winter rapes.

The disclosure relates to a fusion protein including a transcription enhancer and a dCas9 protein, a complex for epigenetic regulation including the fusion protein and one or more guide RNAs (gRNAs), etc.The fusion protein or complex according to an aspect may induce apoptosis of colorectal cancer cells or compensate for rhodopsin deficiency by activating the gene EGFL8, opsin mw, etc., and may be utilized as a pharmaceutical composition or the like for preventing or treating cancer or ocular diseases.

This invention relates to the field of gene technology, and more particularly to the preparation of a zebrafish model lacking Trmt61a enzyme activity, for the purpose of preparing a stable genetic model. trmt61a D181A -P2A-EGFP Knock-in zebrafish strains. This invention utilizes CRISPR / Cas9 technology to... trmt61a d181a trmt61a d181a The mutation site was specifically introduced into the zebrafish genome, resulting in the loss of Trmt61a catalytic activity and tRNA m 1 A zebrafish model with significantly reduced tRNA modification levels. This zebrafish model fills a research gap and provides a basis for tRNA m... 1 A provides a usable in vivo research model for studying the biological developmental regulatory mechanisms related to epigenetic modifications and elucidating the pathological mechanisms of diseases (such as malignant tumors and hematopoietic dysfunction), which can be directly used to explore the core role of this epigenetic modification in development and disease.