32 results about "Nucleosome" patented technology

The invention relates to the field of molecular cytogenetics and potato ploidy breeding, in particular to a potato ploidy identification method for marking and counting chromosome centromere based on a potato CENH3 antibody and a ploidy detection kit. According to the method, the chromosome centromere is marked by specifically recognizing the antibody of the potato centromere nucleosome core histone CENH3 and combining the immunofluorescence technology, so that the accurate counting of the chromosome centromere is realized at the single cell level, and the ploidy of potatoes is judged. The method comprises the following steps: preparing a leaf cell suspension, sequentially incubating a potato CENH3 antibody and a labeled secondary antibody after immobilization, and observing and counting by a microscope after redyeing. The method has the advantages of high species specificity, high throughput and low cost, is not limited by special material taking parts of root tips or shoot tips and cell division periods, can accurately identify the uploid and aneuploid of potatoes, and provides an efficient tool for potato germplasm resource evaluation and cross breeding.

The invention relates to the technical field of crossing of bioinformatics, artificial intelligence and plant genomics, and discloses a plant single cell gene expression prediction method, system, device and medium. A plant single cell gene expression prediction model realizes dynamic feature fusion of a DNA sequence and chromatin accessibility signals through a gated cross attention mechanism; the problem that a traditional single-mode model cannot model regulation and control dynamic association is effectively solved, and the result interpretability is enhanced; a hybrid expert system and a load balancing design are adopted to significantly improve the recognition capability of the model for rare cell types, and a decoupling prediction head design supports efficient transfer learning; a DNA long sequence processing mechanism and nucleosome scale feature coding ensure cross-species compatibility; an end-to-end automatic process and a dynamic parameter optimization framework greatly improve the practicability; a'prediction-verification 'closed-loop support system can be constructed for molecular breeding, and high-precision and interpretable prediction of plant single-cell gene expression is realized.

The present disclosure provides a method for obtaining a cancer risk prediction marker, a cancer risk assessment method, an electronic device, and a storage medium performed by a machine. The method for obtaining a cancer risk prediction marker includes: analyzing a plurality of peripheral blood circulating cell-free DNA (cfDNA) fragments of a biological sample of a subject to obtain sequence reads; obtaining data of a distribution of a nucleosome, and determining a predetermined interval upstream and downstream of a nucleosome center position as a nucleosome protection region; screening sequence reads of partial cfDNA fragments whose ends are located in the nucleosome protection region from the sequence reads of the plurality of cfDNA fragments; calculating a first fragmentation feature in the sequence reads of the plurality of cfDNA fragments, and calculating a second fragmentation feature in the sequence reads of the screened partial cfDNA fragments; and calculating one or more difference values of a change level of the second fragmentation feature relative to the first fragmentation feature as a cancer risk prediction marker.

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.

Methods of determining disease load or type in a subject suffering from a disease associated with cell death of a specific tissue or cell type are provided. Methods of determining a cell free DNA chromatin immunoprecipitation and sequencing (cfChIP-Seq) marker and methods of classifying a subject suffering from a disease are also provided.

Provided herein are methods and systems for detection and monitoring of cancer. The method may comprise use of multiple biomarkers, such as fragmentomics, methylation, and gene expression, or transcription factor activation. The methods and systems may comprise using nucleic acids to generate a fragmentomics profile (e.g., nucleosome profile). The methods and systems may comprise assaying nucleic acids to detect expression of genes of a subject.

For various purposes, a nucleosome signal pattern using fragmentation at a location around a target site is provided. For example, a nucleosome signal pattern may be used to determine methylation levels of a target site (e.g., a CpG site). The signal may be associated with a nucleosome pattern of a cfDNA molecule within a genomic region that is differentially methylated in a target tissue type by having different methylation levels (or levels, e.g., as a pattern) relative to one or more other tissue types (e.g., blood cells). The nucleosome signal pattern can be compared to one or more reference patterns with known methylation levels. Another exemplary method may determine a lesion level in a subject. Another example may determine a proportional concentration of DNA for a particular tissue type.

The present invention provides a method of the identification of a characteristic of cancer, comprising the steps of: (i) contacting a blood sample that contains cell free nucleosomes with a stabilising agent; and (ii) analysing the cell free nucleosomes to identify a cancer characteristic.

The present invention relates to a method of detecting a subject in need of a medical treatment for hemostasis or thrombotic conditions by detecting the level of cell-free nucleosomes or components thereof.

The present invention relates to an extracorporeal device or ex vivo organ perfusion device that includes an in-line monitoring method or device for measuring cell-free nucleosomes, and in particular to an apheresis device that includes a monitoring method or device for measuring cell-free nucleosomes in the blood of a subject.

The present disclosure provides compositions and methods relating to modified mini-nucleosome core proteins and / or delivery of nucleic acids. In particular, the present disclosure includes, among other things, non-viral proteinaceous vehicles for delivery of nucleic acids. In various embodiments, non-viral proteinaceous vehicles provided herein include (a) a nucleic acid binding domain; (b) a targeting domain; (c) a nucleic acid release domain; and, optionally. (d) further domains including, e.g., one or more of a stability domain, an oligomerization domain, and / or a linker domain. In various embodiments, the proteinaceous vehicles include one or more modified residues.

The present disclosure provides a method for enriching for multiple genomic regions using a first bait set that selectively hybridizes to a first set of genomic regions of a nucleic acid sample and a second bait set that selectively hybridizes to a second set of genomic regions of the nucleic acid sample. These bait set panels can selectively enrich for one or more nucleosome-associated regions of a genome, said nucleosome-associated regions comprising genomic regions having one or more genomic base positions with differential nucleosomal occupancy, wherein the differential nucleosomal occupancy is characteristic of a cell or tissue type of origin or disease state.

The invention discloses a method for accurately detecting fetal blood types based on a pregnant woman peripheral blood cff-DNA enrichment method, and belongs to the technical field of biomedical detection. According to the method, an acoustically responsive conformation lock aptamer probe is used, and the probe comprises a recognition domain for specifically recognizing placenta-derived nucleosome and a capture group shielded by an intramolecular conformation lock space. The conformational lock can be selectively opened by a resonant sound field of a specific frequency. In the implementation of the method, the probe in a locked state is mixed with a plasma sample, and then the mixture is processed in the multistage acoustic flow control micro-fluidic chip; and finally, capturing the compound in the activated state through magnetic beads, and eluting to obtain high-purity fetal nucleosome for subsequent DNA extraction and detection. According to the method, efficient, rapid and automatic enrichment of the target object is realized through innovative sequential control of purification and activation in sequence, and the purity and the yield are remarkably improved.

The invention discloses a method and equipment for high-throughput ultramicro analysis of free nucleosome information in peripheral blood. Compared with a traditional method, the method has the advantages that multiple histone modification types of multiple plasma samples can be synchronously detected, the detection efficiency is effectively improved, the detection cost is reduced, the requirement of ultramicro samples is met, and huge clinical application prospects are shown.

Provided herein are improved methods and systems and systems for analyzing cfNA, including improved methods and systems for fragmentomics and their various applications. The methods and systems described herein can be used for assessing gene expression or replication, disease diagnosis, and evaluating immune responses.

To provide compositions and methods for increasing efficiency of targeted genome / epigenetic modification in eukaryotic cells.SOLUTION: A fusion protein comprises at least one nucleosome interacting protein domain linked to a programmable DNA modification protein. A method for increasing efficiency of targeted genome or epigenetic modification in an eukaryotic cell comprises introducing, into the eukaryotic cell, the fusion protein or a nucleic acid encoding the fusion protein.SELECTED DRAWING: None

The present invention relates to a method of profiling covalent DNA modification(s) at a cellular or nuclei level comprising the steps of: providing a sample solution, comprising cell(s) comprising a nucleus comprising genomic DNA; adding a buffer comprising a nucleosome depletion agent to expose the genomic DNA; adding a fusion protein comprising a DNA modification binding domain and a nuclease part; incubating the fusion protein together with the exposed genomic DNA under conditions allowing the fusion protein to bind to the genomic DNA; washing the solution of step (d) with buffer to remove any excess fusion protein; incubating the solution of step (e) under conditions allowing the fusion protein to cut the genomic DNA in proximity of the DNA modification(s); and determining the sequence of the fusion protein incubated DNA of step (e) by high-throughput sequencing, thereby identifying the position(s) of the DNA modification(s) of the genomic DNA that have been sequenced. In other aspects, the invention also relates to a kit for use in performing the method.

The disclosure is related to methods of determining the concentration of cell-free DNA (cfDNA) and methods of determining the short fragment ratio from a mono-nucleosome by capillary electropherogram. In some embodiments, the determined cfDNA concentration and the short fragment ratio from the mono-nucleosome, optionally with a panel of selected protein biomarkers, can be used for effective and affordable multi-cancer early detection.

The present invention relates to method of managing clinical pathways for a patient admitted to hospital, comprising measuring the level of nucleosomes present in a body fluid sample obtained from the patient upon admission to the hospital; and determining the health care actions for the patient based on the level of nucleosomes measured in the sample.

The invention relates to methods and uses of cell free histone H3 isoforms H3.1, H13.2, H3t and / or H3.3 (or cell free nucleosomes containing said isoforms) of determining the origin of a cell free histone or cell free nucleosome in a body fluid sample as originating from a dividing or non-dividing cell.

The invention relates to a ubiquitin modified nucleosome fluorescence resonance energy transfer probe and a preparation method thereof, and belongs to the technical field of protein synthesis. According to the invention, ubiquitin-modified histone is constructed by integrating polypeptide solid-phase synthesis and fragment connection technologies, fluorescent molecular pairs capable of forming fluorescence resonance energy transfer are respectively marked on ubiquitin and DNA, and then the ubiquitin-modified histone and another three histone are assembled into an octamer; and carrying out gradient dialysis on the fluorescence labeled DNA to form a complete nucleosome probe. The probe prepared by the method can be specifically hydrolyzed by histone deubiquitination enzyme, has substrate characteristics close to physiological status, and realizes detection of histone deubiquitination enzyme activity and high-throughput screening of inhibitors through fluorescence resonance signal change. The preparation method has the advantages of high universality, accurate molecular structure and large-scale preparation.

The application discloses a prediction model for simultaneously detecting multiple tumors and performing tissue tracing as well as a training method and application thereof, and relates to the technical field of biological medicine. It is found that nucleosome distribution, fragment size distribution, terminal sequence distribution, genomic instability, gene expression prediction and somatic copy number variation can be used as markers to identify whether a sample to be detected contains any one or more of liver cancer, intestinal cancer, esophageal cancer, pancreatic cancer, lung cancer, gastric cancer, ovarian cancer and nasopharyngeal cancer, and to perform tissue tracing. The application has the advantages of high detection sensitivity, good specificity, high tissue tracing accuracy and low detection cost.

The present invention relates to cell-free nucleosomes as biomarkers in plasma samples of vascular or hematological cancers.

The application discloses an in-vitro detection system, reagent and application of double-modified free nucleosomes in the plasma of pregnant women, and belongs to the technical field of biological medicines.The application discloses an in-vitro detection system of double-modified free nucleosomes in the plasma of pregnant women, which comprises the following modules: a sample processing module, an immune enrichment module, a library construction and sequencing module, a signal processing and feature acquisition module, and a feature screening and model construction module.The in-vitro detection system disclosed by the application takes free nucleosomes in the plasma of pregnant women as a detection object, and provides a complete technical basis for preeclampsia-related epigenetic scoring, candidate marker development and clinical transformation.

The invention relates to the technical field of cell free DNA data detection, in particular to a detection system and method based on cell free DNA fragmentation characteristics, and the system is characterized in that a cfDNA data collection module collects samples from a synthetic data set constructed by a clinical data set and a public data set; the preprocessing module is used for performing whole genome sequencing on the samples and screening qualified data; the feature extraction module generates feature matrixes corresponding to fragment length distribution, end motif distribution and nucleosome distance distribution; supervising a non-negative matrix factorization module to factorize the feature matrix to generate an embedded vector; the classification module adopts pre-training models such as logistic regression and a support vector machine and combines 10-fold cross validation to realize classification. The detection method is executed according to the module process, and the classification capability is improved by supervising non-negative matrix factorization learning features; various cancers can be detected, cancer patients, healthy individuals and non-cancer liver disease patients can be effectively distinguished, and the limitation of a traditional model is solved.

Small cell lung cancer (SCLC) exhibits distinct molecular subtypes characterized by activation of transcription factors (TFs) such as ASCL1, NEUROD1, POU2F3, and REST, but clinical translation has been limited by tissue scarcity. Here, a cell-free DNA (cfDNA) targeted sequencing assay is disclosed that analyzes DNA fragmentation patterns to infer nucleosome profiles at TF binding sites and gene transcription start sites (TSSs) and also detects exonic mutations in certain genes. Application to plasma cfDNA from SCLC patient-derived xenograft models faithfully captured signatures of TF activity and gene expression and revealed a subset of highly informative nucleosome profiling loci including TSSs of key genes including ATOH1, POU2AF2, and targets of SCLC subtype defining TFs. Prediction models of ASCL1, NEUROD1, and REST activity achieved AUCs (0.82-1.00) in SCLC patient samples while a predictor of SCLC vs NSCLC histology achieved an AUC of 0.99. Targeted cfDNA nucleosome profiling can enable SCLC subtyping to improve patient care.

The invention relates to the measurement of cell free nucleosomes for the selection of biological samples for DNA sequencing. The invention also relates to using the measurement of cell free nucleosomes to determine the volume of body fluid sample required to obtain a required level of DNA for DNA sequencing.

The present invention relates to methods for determining the concentration of cell-free DNA (cfDNA) from capillary electropherogram and calculating the proportion of short fragments from mono-nucleosomes. In some embodiments, the determination of cfDNA concentration and mono-nucleosome short fragment proportion, optionally in combination with a panel of screened protein biomarkers, can be used to achieve efficient and cost-effective early detection of multiple cancer types.

The present invention relates to a method of analyzing cancer comprising detecting or measuring the trimethylation (H3K27Me3) level of lysine 27 on histone H3 of cell-free nucleosomes in a bodily fluid sample obtained from a subject, as well as related uses and kits using said method.