234 results about "Chromatin" patented technology

The invention discloses a rice nitrogen response regulation and control network analysis and breeding target identification system and method based on multi-omics data. According to the system, organic combination of regulation and control network construction based on single or multiple varieties of materials, key transcription factor recognition and accurate positioning of regulation and control areas where transcription factors play roles is achieved through an expression-chromatin accessibility correlation research method, and cis-trans effect distinguishing of the regulation and control areas is achieved through a deep learning model. The method comprises the following steps: carrying out nitrogen starvation pretreatment on rice, then carrying out nitrogen resupply, collecting a root sample, and carrying out ATAC-seq and RNA-seq sequencing; an eCAAS method is adopted to construct a regulation and control network, and key transcription factors are identified and accurately positioned; the chromatin accessibility difference of different varieties is predicted through a deep learning model, the cis-action effect and the trans-action effect are distinguished, an upstream transcription factor target is provided for genes dominated by the trans-effect, and haplotype and editable regulatory region targets available for direct breeding are provided for genes dominated by the cis-effect.

The invention provides a single-cell multi-omics cell type annotation method based on distribution and knowledge alignment, and belongs to the technical field of single-cell type annotation, the method comprises the following steps: obtaining single-cell transcriptome data and single-cell chromatin accessibility sequencing data, and pre-training and training a multi-omics variation auto-encoder model, the multi-omics variational auto-encoder model is combined with a variational auto-encoder and a knowledge distillation technology, and multi-omics single cell data is integrated and annotated through distribution and knowledge alignment. And performing cell type prediction on the single cell transcriptome data and the single cell chromatin accessibility sequencing data which are input at the same time by using the trained multi-omics variational auto-encoder model. According to the method, the problem of limitation of a method only depending on single omics is solved, the synergistic effect between the omics is enhanced, the accuracy of annotation is improved, and the calculation overhead is reduced through knowledge distillation.

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.

The present invention relates to a chromatin open site marker associated with the identification and early screening of high-risk populations for colorectal cancer and its application. The marker is rs10871066. Large-scale population data and biological functional experiments have confirmed that the rs10871066 site has functional regulatory activity, and individuals carrying the rs10871066[A] genotype are more likely to bind to the transcription factor FOXP1, while individuals carrying the rs10871066[G] genotype are more likely to bind to the transcription factor TCF7L2, thereby affecting the chromatin interaction between the region and the promoter of the target gene, promoting the expression levels of the target genes PIBF1 and KLF5, and thus promoting cancer cell proliferation, ultimately leading to an increased risk of colorectal cancer in individuals. By detecting the rs10871066 risk site in normal people, high-risk populations for colorectal cancer can be identified, assisting in the diagnosis of colorectal cancer patients.

Embodiments of systems, methods, and compositions provided herein relate to assays for selectively controlling enzymatic reactions. Some embodiments relate to methods of inhibiting, reducing, or eliminating secondary DNA (such as mitochondrial DNA) sequencing reads from open chromatic sequencing, whole genome sequencing, or targeted sequencing.

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 an efficient extraction method of blue fox sperm DNA, and belongs to the technical field of molecular biology. Aiming at the structural characteristics that chromatin of the blue fox sperms is highly condensed, histone is replaced by protamine, and a stable nucleoprotein complex is formed through an intermolecular disulfide bond, the invention provides an efficient DNA extraction method suitable for the blue fox sperms. According to the method, based on the synergistic effect of three chemical reagents, namely SDS, PK and DTT, full lysis of the sperm cells of the blue foxes is achieved, and then efficient enrichment of sperm DNA of the blue foxes can be achieved by combining a conventional DNA extraction method. According to the efficient extraction method of the blue fox sperm DNA provided by the invention, the yield and integrity of the blue fox sperm DNA are remarkably improved, and the limitation that sperm chromatin is difficult to effectively lyse by a conventional method is overcome; the method provides reliable technical support for research on genetic diversity evaluation, population management, molecular breeding and the like of the blue foxes, and has the potential of popularization and application in other high-condensation sperm species.

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 discloses a chromatin contact atlas-based topological correlation domain division method, which comprises the following steps of: acquiring and preprocessing chromatin contact atlas data, and constructing a normalized contact matrix; according to the normalized contact matrix, calculating single-segment Infomap entropy values of all possible division intervals; solving an Infomap entropy value of a minimum part in each state through dynamic programming recursion, and calculating a complete Infomap entropy value under each step number according to the Infomap entropy value of the minimum part in each state; selecting the step number corresponding to the minimum integral Infomap entropy value, and obtaining the optimal topological correlation structure domain division through backtracking; an approximation error of the partition structure is calculated to assess partition accuracy. According to the method, a machine learning model does not need to be trained, whole genome chromatin contact information can be fully utilized, optimal division of TAD is automatically achieved, the division accuracy and repeatability are improved, meanwhile, the calculation complexity and cost are reduced, and an efficient and reliable tool is provided for chromatin three-dimensional structure and gene regulation and control research.

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 invention relates to the technical field of embryonic development evaluation, and discloses an embryonic chromatin openness and gene expression evaluation method, which comprises the following steps: extracting an embryonic cell sample with a survival rate of more than or equal to 95% through a micromanipulation technology; acquiring chromatin open signal data by adopting an ATAC-seq technology; carrying out genome positioning by utilizing a BWA comparison tool, and constructing a three-dimensional contact matrix through a matrix decomposition algorithm in combination with Hi-C data; determining the gene expression quantity by adopting fluorescent quantitative PCR (Polymerase Chain Reaction); and constructing an XGBoost integrated learning model to fuse chromatin characteristics and gene expression data. By optimizing micromanipulation parameters and an ATAC-seq experimental process, the cell survival rate is increased to 95.2 + / -1.3%, the ATAC-seq library complexity reaches 85.3%, and Hi-C data standardization processing is combined, so that the technical problem of data deviation is solved, and the embryo sample processing efficiency and data reliability are remarkably improved.

The invention provides a method for predicting pathogenicity of functional non-coding copy number variation in brain diseases, and belongs to the technical field of bioinformatics. Comprising the steps that brain-related features are collected to construct a brain-related feature set, and the types of elements in the brain-related feature set comprise transcription factor binding sites, histone modification and chromatin accessibility; constructing a hybrid model fusing two-dimensional convolution and swing-transformer for capturing collaborative regulation characteristics of brain-related cis-regulatory elements in the DNA sequence and generating N-dimensional brain-related functional feature annotations, and training the hybrid model by using a brain-related feature set; cNV data sets of the two pieces of brain-related copy number variation data are constructed, the data types in the mixed data set comprise coding and non-coding, and the high-confidence non-coding data set only comprises non-coding data; training a random forest model based on the two CNV data sets; the hybrid model and the random forest model jointly form a DeFunCNV model, and the pathogenicity of functional non-coding copy number variation in brain diseases is predicted.

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.

Provided herein are, inter alia, are methods and systems for amplifying a chromosomal fragment DNA sequence. The methods and systems provided herein are, inter alia, useful for detecting copy number variation, structural variation, and / or extrachromosomal DNA within the chromosomal DNA of a plurality of cells. In addition, the methods provided herein are, inter alia, useful for jointly analyzing chromatin architecture and gene expression at a single cell level. The methods provided herein can be, inter alia, used to analyze chromosomal heterogeneity, clonal shifts, and / or evolutionary shifts between different cells.

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 invention discloses a method for inhibiting lipid metabolism of nasopharyngeal carcinoma (NPC) through an LncRNA ANRIL-ZBTB7A pathway. The invention relates to a method for inhibiting lipid metabolism of nasopharyngeal carcinoma by using an LncRNA ANRIL-ZBTB7A pathway, which comprises the following steps: carrying out modification treatment on LncRNA ANRIL so as to negatively regulate an SREBF1-FASN factor and further inhibit lipid metabolism of NPC; when the transformation treatment mode is that the LncRNA ANRIL is over-expressed, the ZBTB7A is knocked down. According to the application disclosed by the invention, the LncRNA ANRIL is combined with shZBTB7A and an SREBP inhibitor famostatin, so that the lipid metabolism of NPC is inhibited, and an important role is played in research and development of targeted therapeutic drugs. The independently designed primer sequences of the chromatin immunoprecipitation-quantitative polymerase chain reaction of the LncRNA ANRIL, the SREBF1 and the FASN can be used as a new way for researching the NPC.