146 results about "Chromatin" patented technology

The invention relates to a biological information data processing technology, in particular to a method for analyzing a single-cell Hi-C regulation scale chromatin band, which comprises the following steps: preprocessing single-cell Hi-C data to generate pseudo-batch Hi-C data; performing normalization processing on the pseudo batch Hi-C data to extract a Hi-C contact matrix of each chromosome; identifying and detecting false batch strips from the Hi-C contact matrix; projecting the pseudo batch strips to the original single cell Hi-C data to obtain single cell strips; and carrying out quantitative analysis on the single-cell strip in the original single-cell Hi-C data. According to the method, the regulation and control scale chromatin bands with definite endpoints and directivity can be stably identified, and a band set with remarkable statistics is output.

The invention discloses a neural network calculation method and device for gene expression regulation and control analysis, and relates to the technical field of bioinformatics, and the method comprises the steps: obtaining first feature data and second feature data; constructing an input feature comprising a plurality of regulation and control hierarchies; and inputting the input features of the plurality of regulation levels and the second feature data into the target neural network model, and outputting a prediction result of the gene expression state. According to the neural network calculation method provided by the invention, chromatin accessibility and three-dimensional space interaction data are deeply fused through a dynamic routing module, so that the problem of'black box 'which is inaccurate in prediction and difficult to explain in a traditional deep learning model is solved in a mode of explicitly simulating a real biological regulation mechanism; and a key gene regulatory pathway can be accurately identified.

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, the inventors conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin remodelers. They revealed that the histone H3 methyltransferase SETDB1 plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 knockdown triggers decreased expression of genes related to replication and cell cycle and promotes growth arrest associated with increased markers for DNA damage and senescence entry. Using pre-clinical model, they further demonstrated that anti-SETDB1 therapy tumor growth in vivo. The inventors identify SETDB1 as a new relevant therapeutic target for the treatment of metastatic uveal melanomas. The present invention relates to a method for treating uveal melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of SETDB1 inhibitor.

The invention discloses a Rongchang pig T2T genome assembly method. The method comprises the following steps: 1) collecting and sequencing a sample; 2) genome investigation and assembly; 3) genome annotation; wherein in the sequencing step, three sequencing technical means, namely, a three-generation gene sequencing technology PacBio, Nanopore PromethION 48 short reading and chromatin conception capture (HiC), are adopted, and the Rongchang pig genome is subjected to sequencing and sequence splicing together. The Contig N50 value of the genome is nearly three times that of Sscrofa11.1, and the improvement is mainly embodied in a complex genome region (centromere and telomere regions), so that the genome becomes the most complete genome available at present.

Multi-scale footprinting of DNA-protein interactions is described. Multi-scale footprint scores may be generated based on chromatin accessibility data, the multi-scale footprint scores indicating protein binding to positions of a genome at different protein size scales. A deep learning model may be trained using the multi-scale footprint scores and corresponding DNA sequences. DNA-protein interactions for a DNA sequence of interest may be predicted using the trained deep learning model. The prediction may include generating sequence attribution scores for the DNA sequence of interest using the trained deep learning model and predicting transcription factor binding sites of the DNA sequence of interest based on the sequence attribution scores.

A method for predicting a CTCF chromatin loop on the basis of a transcription factor sequence in a loop extrusion model, comprising: constructing a data set; converting a key transcription factor sequence; establishing a CTCF chromatin loop classification model on the basis of the key transcription factor sequence; and evaluating the model. In the method, a transcription factor binding order is encoded into a transcription factor sequence, and the transcription factor sequence is decoded by utilizing a pre-trained natural language BERT model, thereby achieving the prediction of the CTCF chromatin loop. The method not only improves the prediction accuracy but also enhances the interpretability of a predictive model.

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.

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same for the modulation of one or more SWI / SNF-related matrix associated actin dependent regulator of chromatin subfamily A (SMARCA) and / or polybromo-1 (PB-1) protein via ubiquitination and / or degradation by compounds. The compounds are bifunctional molecules that link a cereblon-binding moiety to a ligand that binds SMARCA and / or PB1 proteins.

The invention discloses an application of SNF2 protein derived from streptococcus angina extracellular vesicles in gastric cancer prognosis. The chromatin remodeling protein SNF2 derived from S.anginosus EVs can be combined with a transcription factor TEAD1, so that the transcription of the palmitoyl transferase ZDHHC11 is promoted together. Then, the stability of the ZDHHC11 is enhanced by catalyzing palmitoylation of PD-L1, and finally immune escape is induced. In addition, SNF2 also can activate AXL, CTGF, CYR61 and other carcinogenic targets at the downstream of TEAD1, thereby further accelerating the malignant progression of gastric cancer. In an in-vivo experiment, the intragastric administration of the S.anginosus EVs not only promotes the tumor growth of mice, but also significantly inhibits the infiltration of CD8 + T cells. Blocking of ZDHHC11 can effectively reverse immune escape, and has a synergistic effect with an anti-PD-1 therapy, so that the treatment effect is remarkably improved.

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.

Provided are a truncated chromatin opening element and a combination thereof, an expression system comprising the chromatin opening element or the combination thereof and applied to eukaryotic cells, and use thereof. The chromatin opening elements are truncated sequences of two chromatin opening elements from different sources, respectively, and can be used alone or in combination. The chromatin opening element significantly shortens the effective sequence, thereby facilitating the integration of a vector comprising the element or the combination thereof with other elements, such as integration with ITR, achieving semi-site-specific integration in the presence of the PiggyBac transposase, and then using a bulkpool rapid screening process to shorten the protein production and cell strain construction cycle by about 4-5 weeks while maintaining comparable yields.

Discussed herein are novel engineered polypeptides which are effective at cutting and tagging H3 histone tails from endogenous histones, facilitating multiplex "cut-and-paste" middle down proteomics with tandem mass tags. This cut-and-paste proteomics approach permits the quantitative analysis of H3 histone modification crosstalk after treatment with different histone deacetylase inhibitors.

The present disclosure includes, among other things, methods, kits, and systems for determining a status of lung cancer. In various embodiments, the present disclosure relates to the use of one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and / or DNA methylation as features of a status of lung cancer. In some embodiments, differential modifications and / or differential accessibility are detected and quantified at one or more genomic loci in a biological sample, e.g., cell-free DNA (cfDNA), from a liquid biopsy sample obtained or derived from a subject having lung cancer. In various embodiments, the determined status can be used, e.g., to select a treatment for lung cancer and / or to treat lung cancer.

The invention relates to the technical field of gene engineering, in particular to an HDR enhancer for improving cell homologous recombination efficiency and application of the HDR enhancer, and the HDR enhancer for improving the cell homologous recombination efficiency comprises an inhibitor of a non-homologous end connection repair pathway and an intracellular homologous recombination accelerant; the inhibitors of the non-homologous end connection repair pathway are SCR-7 and M3814, the intracellular homologous recombination accelerators are L755507 and Romidepsin, the four agents synergistically target an NHEJ signal pathway, the cell cycle, chromatin structure opening and HDR signal pathway are regulated and controlled at the same time, and the problem that an existing reagent for improving the cell homologous recombination efficiency is insufficient in synergistic effect is solved.

Provided are a single-cell chromatin accessibility and transcriptome combined sequencing method and application thereof. The method comprises: treating a cell nucleus using a transposase to obtain gDNA of a chromatin open region connected with a first specific tag sequence; treating the cell nucleus using a transcriptome capture sequence to obtain cDNA connected with a second specific tag sequence; generating a droplet based on a droplet microfluidic to seal the cell nucleus and a first microbead in the droplet, wherein the gDNA and the cDNA are captured by the first microbead, and wherein more than one cell nucleus is sealed in the droplet; and sequencing the gDNA and the cDNA to obtain combined information of single-cell chromatin accessibility and transcriptome according to the first specific tag sequence and the second specific tag.

The disclosure relates to targeted Chromatin Accessibility and Mutation Sequencing (tCAM-seq) for parallel analysis of genetic and epigenetic analysis of patients with pancreatic adenocarcinoma (PDAC) to 1) determine responsiveness to standard of care chemotherapy, and 2) identify actionable allelic variant mutations that can be used to guide treatment decisions. Prognostic methods and treatment strategies are also provided.

The present disclosure includes, among other things, methods, kits, and systems for determining the status of MS in a subject. In various embodiments, the present disclosure relates to the use of one or more histone modifications, chromatin accessibility, binding of one or more transcription factors, and / or DNA methylation that are characteristic of the status of MS. In some embodiments, differential modifications and / or differential accessibility are detected and quantified, at one or more genomic loci of a biological sample, e.g., in cell-free DNA (cfDNA) from a liquid biopsy sample obtained or derived from a subject with MS. In various embodiments a determined status is useful, e.g., in selecting treatment for and / or treating MS.

The application relates to the technical field of image processing, in particular to an abnormal cell screening method and system based on image analysis, which comprises the following steps: acquiring continuous image frames of a staining process, extracting average optical density, integral optical density and chromatin gray standard deviation of sample cells as staining parameters, and acquiring chromatin texture; forming a staining parameter space curve with the change of the staining parameters over time, fitting to obtain a continuous staining curve; aligning and fitting the continuous staining curve with a standard parameter curve calibrated in advance to obtain a coordinate transformation vector; acquiring an image frame after the completion of the staining, performing standardization correction on the staining parameters of the to-be-tested cells by using the coordinate transformation vector to obtain chromatin texture features, and then performing feature comparison and identification on abnormal cells. The application reduces the staining sensitivity difference caused by biological factors such as individual gene expression difference, different cell membrane protein compositions and pH value changes, and eliminates the influence of staining condition difference and equipment difference among different laboratories on the screening result.

The present application relates to biological information data processing technology, and is a method for single-cell Hi-C regulatory scale chromatin band analysis, comprising the following steps: preprocessing single-cell Hi-C data to generate pseudo-bulk Hi-C data; normalizing the pseudo-bulk Hi-C data to extract the Hi-C contact matrix of each chromosome; identifying and detecting pseudo-bulk bands from the Hi-C contact matrix; projecting the pseudo-bulk bands onto the original single-cell Hi-C data to obtain single-cell bands; and quantitatively analyzing the single-cell bands in the original single-cell Hi-C data. The present application can stably identify regulatory scale chromatin bands with clear endpoints and directionality, and output statistically significant band sets.

This application provides a method for constructing single-cell libraries of biomaterials embedded in hydrogels, which can be used for constructing libraries of mitochondrial DNA and / or open chromatin regions and / or 3' transcriptome (RNA).

The application provides a non-coding mutation-induced risk gene expression up-regulation and down-regulation prediction method and system, comprising the following steps: step 1, obtaining a data set and performing pretreatment; step 2, information input standardization between non-coding mutations and gene transcription start points TSS; step 3, non-coding mutation information input standardization; step 4, sequence length alignment and representation learning framework; and step 5, embedded feature merging and prediction output. The application is matched with chromatin accessibility sequencing data to migrate to any tissue or cell type, make accurate and reliable prediction, and utilize an attention mechanism to endow the model with interpretability.

The present application relates to the technical field of digital pathology image analysis, and discloses an animal tissue pathological section cell atypia image automatic grading method and system, the method comprises the following steps: scanning the whole section image to obtain a high-power field image by traversing the tumor area with a sliding window; inputting a star-convex polygon regression kernel instance segmentation network trained by multi-species animal tumor annotation data to obtain each nuclear boundary; extracting morphological parameters such as nuclear area, long-short axis ratio, nuclear-plasma ratio, nuclear membrane regularity and chromatin texture; detecting and counting nuclear mitotic figures; introducing a species adaptive baseline correction to normalize the morphological parameters and then inputting the normalized morphological parameters into a classifier to output a three-level atypia grading.

The application discloses a kind of plant whole genome RNA-chromatin interaction detection methods, the method includes the interaction state of fixed RNA and chromatin, preparation double link, obtain nuclear, chromatin DNA fragment, RNA / linker / DNA chimera, RNA-DNA double-stranded complex in turn;Tn5 transposase fragmentization cuts double-stranded complex;PCR amplification forms DNA library.The application applies Tn5 transposase to the original RADICL-seq method, successfully to RNA-DNA complex is cut and library, greatly simplifies the process, experimental procedure is reduced by at least half, experimental period is shortened from 4-5 days to 3 days, the fragment size of DNA library produced is between 250bp-400bp, increase the length of final effective RNA / DNA fragment pair, thereby greatly improve the efficiency when aligning to plant genome in subsequent bioinformatics analysis, provide effective means for plant whole genome RNA-chromatin interaction detection.

The application provides an application of AU15330 in preparation of a medicine for treating hepatitis B or inhibiting HBV. The application proves that AU15330 can inhibit the transcription activity of cccDNA by inhibiting the accessibility of HBV cccDNA chromatin, thereby reducing the replication ability of HBV. The application provides a new medicine for treating hepatitis B and related diseases such as hepatocellular carcinoma, and the target point also provides a new selection for the development of other such medicines.

The present invention belongs to the field of biotechnology. In particular, the present invention relates to a method for detecting chromatin accessibility or DNA binding protein footprint in cells based on a two-enzyme method. More specifically, the present invention relates to a method for converting information on the openness of chromatin into information on mutations in DNA sequences by means of adenine methyltransferase and adenine deaminase, thereby quantitatively determining the chromatin accessibility of DNA molecules and the binding footprint of DNA binding proteins, such as transcription factors.

The invention discloses a cancer-specific chromatin accessibility marker-based tissue origin inference method and device and a storage medium, and belongs to the technical field of gene detection. The method aims to solve the problem that low-cost shallow whole genome sequencing data is difficult to carry out accurate cancer traceability. The invention provides a fragment discreteness index which is combined with terminal dispersity and coverage fluctuation of free DNA fragments so as to more accurately characterize chromatin accessibility. And through a global and local combined statistical test strategy, identifying candidate accessibility regions from the data. The method comprises the core step of screening out a unique marker of a specific cancer species by removing a common accessibility region in various cancers and healthy control. Based on the specific markers, multi-dimensional fragment omics features are extracted, a machine learning multi-classification model is constructed, and the probability that a to-be-detected sample comes from different cancer types is predicted.

The application discloses a method for biosynthesis of gene or gene cluster product based on chromatin three-dimensional structure, and belongs to the field of genetic engineering. The method can realize the improvement of the target gene or gene cluster product by the directional integration of the target gene or gene cluster into the strong correlation chromatin region with high frequency interaction on the genome. The method has the characteristics of simple implementation, good repeatability, remarkable effect and the like, and can be widely applied to the improvement of the target gene or gene cluster product.

A novel ubiquitous chromatin opening element (UCOE) named SRF-UCOE and methods for its use are provided. Compositions including recombinant and synthetic SRF-UCOE nucleic acid molecules, DNA constructs and vectors comprising the SRF-UCOE nucleic acid molecules, host cells comprising the DNA constructs or vectors, and cell culture systems comprising such host cells. SRF-UCOE polynucleotide sequences can be used in DNA constructs or expression cassettes for transformation and expression in cells or organisms of interest. The compositions and methods provided are useful for increasing and / or maintaining expression of a gene of interest. Transgenic cells, tissues, and animals comprising a SRF-UCOE nucleotide sequence are also provided. Methods are provided for increasing and / or maintaining expression of a gene of interest and for treating a subject via gene therapy.

The invention discloses a gene expression profile prediction method and device, electronic equipment and a storage medium, and relates to the technical field of artificial intelligence. Specific genetic variation and regulation region sequences in a peripheral blood sample are detected, and a standardized SNP genotype matrix and a regulation annotation vector are obtained; constructing a gene-pathway-disease-drug four-layer regulation and control network based on multi-source heterogeneous data, and determining a core node gene based on the constructed network; obtaining LD structure information and chromatin accessibility characteristics corresponding to the core node gene; and taking the standardized SNP genotype matrix corresponding to the core node gene, the regulation and control annotation vector, the LD structure information and chromatin accessibility characteristics as input of a pre-trained gene expression profile prediction model to obtain a gene expression profile prediction value of an individual corresponding to the peripheral blood sample in a specified brain region. Therefore, an accurate mapping relation between the blood gene expression data and the gene expression data of the targeted CNS tissue is established.

Described herein are compositions, kits, and methods for chromatin accessibility measurement using genome editing by double-stranded DNA cytosine deaminases (Ddds).