31 results about "Methylation Site" patented technology

This invention discloses a method for constructing a gene methylation diagnostic model for differentiated thyroid cancer (PTC). The method includes the following steps: S1, obtaining a test sample; S2, extracting and storing DNA from the test sample; S3, performing methylation analysis; S4, establishing a diagnostic model based on DNA methylation, where the model shows that patients with cg03596178, cg06033721, cg06688989, cg07209244, cg07485775, cg14484681, cg19979108, and cg20943461 are more likely to experience disease progression and are considered risk factors; S5, cross-validating and evaluating the performance to obtain the gene methylation diagnostic model. This model, by detecting and statistically analyzing specific methylation sites, can differentiate patients with recurrent or metastatic characteristics in differentiated thyroid cancer. The relevant model can assist in the clinical diagnosis and follow-up of thyroid patients.

A method, apparatus, storage medium, and program product for tracing the source of disease-affected tissues or organs, the tracing method comprising: acquiring methylation data of multiple tissues or organs, wherein the methylation data of the tissues or organs are methylation data of healthy tissues or organs; establishing an average methylation rate matrix based on the methylation data of multiple tissues or organs, wherein the average methylation rate matrix includes the average methylation rate of each tissue or organ at multiple methylation sites or methylation regions; determining specific methylation sites or specific methylation regions based on the average methylation rate matrix; acquiring methylation data of a sample to be traced; and performing tracing based on the average methylation rate of multiple tissues or organs at the specific methylation sites or specific methylation regions and the methylation data of the sample to be traced.

The application discloses a kind of based on DNA methylation's construction method of biological age prediction model, the application is downloaded from GEO data website, derived from Chinese population, contains calendar age data, whole blood sample 450k methylation chip data, by the method of elastic network combined bootstrap, 31 methylation sites of modeling candidate are screened, multiple linear regression, support vector machine, random forest and gradient boosting regression tree are used to carry out preliminary construction and evaluation of model, then further filter methylation sites using full subset regression, obtain methylation age prediction model based on 18 methylation sites.Finally, using any provincial team natural population data, methylation age prediction model is optimized, and finally the biological age prediction model based on 18 methylation sites is obtained.The model is suitable for Chinese population, the number of methylation sites contained is less, is not affected by blood cell components, and the prediction accuracy is good.

The application discloses a DNA methylation site marker for detecting hepatocellular carcinoma, a multiplex dPCR kit and a diagnostic model construction method. The DNA methylation site marker comprises cg02829688, cg13080379, cg03760839, cg10703826, cg12664119, cg16990168 and cg23371746 sites. The application designs a primer probe group for the above sites, constructs a multiplex dPCR kit of a double reaction system, realizes quantification of target DNA methylation sites, takes the methylation levels of the 7 sites as characteristic variables, adopts an XGBoost algorithm and / or an LR algorithm to construct a diagnostic model. Experimental verification shows that the model can effectively distinguish hepatocellular carcinoma patients from liver cirrhosis, chronic hepatitis B, metabolic dysfunction-related fatty liver disease patients and healthy individuals, especially shows good efficiency in auxiliary diagnosis of early hepatocellular carcinoma, and provides a new technical scheme for clinical diagnosis and screening of hepatocellular carcinoma.

This invention relates to the field of biotechnology, and in particular to a primer-probe combination for detecting methylation sites in cancer and its applications. This invention is the first to discover that abnormal methylation at specific sites of the TRIB3 gene is significantly associated with the occurrence and development of colorectal cancer, and abnormal methylation at specific sites of the MAPT gene is significantly associated with the occurrence and development of gastric cancer. This correlation has not been publicly reported in the prior art, possessing novelty and significant clinical application value. The primer-probe combination provided by this invention is used to detect the methylation status of the TRIB3 gene or the MAPT gene in a sample. Specifically, when the primer-probe combination is used to detect the methylation level at specific sites of the TRIB3 gene, it can be used for the auxiliary diagnosis, early screening, or risk assessment of colorectal cancer; when the primer-probe combination is used to detect the methylation level at specific sites of the MAPT gene, it can be used for the auxiliary diagnosis, early screening, or risk assessment of gastric cancer.

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

The application discloses a methylation marker combination for detecting early gastric cancer and application thereof. The marker combination comprises 146 methylation sites of 11 DNA regions and a transformation rate control marker region, and the methylation levels of the target regions are significantly different between early gastric cancer patients and healthy people. The kit of the application contains reagents for detecting the methylation degree of the above sites, and supports various high-throughput sequencing methods. The detection system adopts a logistic regression model to calculate a prediction value, multiplies the average methylation rate of each region by a corresponding weight coefficient, adds them together, and compares the sum with a threshold value to make a positive judgment. The application realizes high sensitivity and high specificity for non-invasive early detection, is particularly suitable for non-invasive screening of plasma free DNA samples, can effectively improve the survival rate of gastric cancer patients, can significantly reduce medical expenses, and has a wide clinical application and industrial utilization prospect.

The application discloses a nucleic acid sequence construction method for cfDNA multiplex gene methylation detection and application thereof. The construction method comprises the following steps: using a methylation-sensitive restriction endonuclease to perform enzyme cutting on to-be-detected cfDNA to obtain enzyme cutting fragments, using a ligase to connect an adapter to a nick end of the enzyme cutting fragments to form an adapter product; and using the adapter product as a template to perform PCR amplification to construct a recombined nucleic acid sequence for target gene methylation site detection. The construction method can be used for cfDNA level methylation qPCR analysis and low-abundance sample quantitative analysis, has small sample demand, has a wide methylation analysis coverage, and has high methylation enrichment efficiency.

The application provides a Septin9 methylation detection composition and application thereof, and the composition comprises a methylation-dependent restriction enzyme, a capture oligonucleotide, a universal primer and a Septin9 methylation-specific primer; the capture oligonucleotide comprises a first universal sequence, a folding sequence and a binding capture sequence from 5' end to 3' end in sequence; the folding sequence is at least partially identical to a 5' end sequence of a Septin9 methylation site after the methylation-dependent restriction enzyme is cut; and the binding capture sequence is specifically bound to a fragment region where the detected Septin9 methylation site is located. The application is based on a methylation-dependent restriction enzyme and a universal primer fluorescence quantitative PCR technology, does not need bisulfite conversion, and realizes accurate and specific Septin9 methylation detection.

The application discloses a methylation marker combination for detecting early esophageal cancer and application thereof. The marker combination comprises 178 methylation sites of 12 specific DNA regions and a specific internal marker region, and the methylation levels of the regions in plasma of patients with early esophageal cancer and healthy people are significantly different. The application also provides a primer combination and a kit for detecting the marker combination, and supports high-throughput deep sequencing. A detection system is used to extract plasma free DNA, perform bisulfite conversion and amplification, calculate a prediction value by using a logistic regression model, multiply the average methylation rate of each region by a corresponding weight coefficient, and compare the result with a threshold value to make a positive judgment. The application greatly improves the detection sensitivity of non-invasive screening for early esophageal cancer under the premise of ensuring high specificity, and has a wide clinical application prospect.

The application discloses a method and system for correcting Hi-C sequence alignment by fusing DNA methylation information, and the method comprises the following steps: obtaining a preliminary alignment result of Hi-C sequencing of a sample genome relative to a reference genome and a methylation site map; obtaining a corresponding candidate alignment position and an original sequence alignment score of each read pair; positioning an alignment interval on the reference genome at both ends of each candidate alignment position; based on the methylation site map, counting the number of methylation sites covered at both ends of the candidate alignment position to obtain a methylation penalty score representing biological consistency; obtaining a recalibration comprehensive score based on the methylation penalty score, reordering all candidate alignment positions of the read pair, calculating an alignment quality update value of each candidate position, and outputting a corrected alignment result. The application solves the problem that in a polyploid and a highly repetitive genome, multiple alignment of Hi-C reads cannot accurately determine the real source position.

The present invention provides a method for determining the risk of death and / or the probability of a healthy lifespan of a dog; the method comprising a) providing a DNA methylation map from a sample obtained from the dog; and b) using the DNA methylation map to determine the risk of death and / or the probability of a healthy lifespan of the dog; wherein the DNA methylation map contains at least one methylation site as listed in Table 1.

This invention provides a method for predicting protein methylation sites that integrates quantum and region-aware technologies, comprising the following steps: Step 1, obtaining protein sequences as data sources and constructing training and independent test sets respectively; Step 2, constructing multimodal features for each protein sequence using a three-way nested scattering network, fusing the multimodal features to obtain an optimized fused feature tensor; Step 3, inputting the optimized fused feature tensor into a RaQMeNet network model to perform methylation site prediction. This invention not only significantly outperforms existing technologies in terms of performance indicators but also possesses stronger adaptability, stability, and interpretability. It can be widely applied in multiple bioinformatics and biomedical fields such as protein functional annotation, disease mechanism research, and drug target discovery, demonstrating promising application prospects and commercial value.

This invention provides a DNA methylation biomarker, kit, and device for detecting type 2 diabetes, relating to the field of disease diagnostic technology. The DNA methylation biomarker provided by this invention exhibits high sensitivity and specificity. It can be detected using the TaqMan probe method, and the detection is convenient, safe, and suitable for large-scale screening. The kit provided by this invention includes primers and probes for detecting the methylation level of the DNA methylation site cg27467803. By detecting the methylation degree of the DNA methylation site cg27467803, the risk of developing type 2 diabetes in a subject can be predicted, providing a basis for the early prediction and diagnosis of type 2 diabetes. The device provided by this invention has a simple structure and can accurately detect the risk of developing type 2 diabetes in a subject.

This invention discloses a plasmon resonance detection method for hepatobiliary-specific methylation sites. The method first immobilizes a sequence-specific DNA capture probe on a gold membrane surface and covalently couples it with a methylation-binding domain protein, constructing a sensor interface with dual functions of sequence capture and methylation recognition. During detection, a pre-treated plasma circulating cell-free DNA single-stranded sample is introduced into the sensor. The target DNA first hybridizes with the capture probe, and then its methylation site is specifically bound by the adjacent methylation-binding domain protein, triggering two consecutive specific surface plasmon resonance signal responses. By analyzing the increment between the two stable signal values ​​and comparing it with a preset threshold, label-free, real-time, and highly specific determination of the methylation status of the target site can be achieved. This invention eliminates the need for bisulfate treatment, effectively preserving DNA integrity, and is particularly suitable for high-sensitivity detection of hepatobiliary disease-related epigenetic markers in trace circulating cell-free DNA.

The application relates to the technical field of melanoma prognosis, and provides a construction method and a verification method of a melanoma prognosis model based on a lactation gene methylation feature. The DNA methylation data of a cancer genome atlas database is taken as a training set, and the DNA methylation data of a gene expression comprehensive database is taken as a verification set, so that the lactation-related gene methylation feature prognosis marker model of melanoma constructed has good external applicability. A methylation site pair matrix is constructed through the relative methylation order relationship of the methylation sites, so that the batch effect between different data sets is effectively avoided, and excellent robustness and clinical applicability are achieved. The methylation sites corresponding to the lactation-related gene set are taken as anchor points to perform hierarchical clustering and differential methylation site screening, functional sites related to prognosis are screened out, the reliability of the constructed prognosis marker model is improved, and the accuracy of prognosis prediction is improved.

This invention provides an SDC2 methylation detection kit and its application. The kit includes a methylation-dependent restriction endonuclease, a capture oligonucleotide, and universal primers. The capture oligonucleotide includes a first universal sequence, a folded sequence, and a binding capture sequence from the 5' end to the 3' end. The folded sequence is at least partially identical to the 5' end sequence of the SDC2 methylation site after digestion with the methylation-dependent restriction endonuclease. The binding capture sequence specifically binds to the fragment region containing the detected SDC2 methylation site. This invention, based on methylation-dependent restriction endonuclease and universal primers, utilizes real-time quantitative PCR technology, eliminating the need for bisulfite conversion, and achieves sensitive and specific detection of SDC2 methylation with a detection limit as low as 10 copies / reaction.

This invention relates to the field of biotechnology and discloses a multiplex fluorescent PCR detection system and its applications. The multiplex fluorescent PCR detection system includes 22 primer pairs, and discloses primer sequences targeting 22 sites, used to simultaneously amplify 15 detection sites and 7 internal reference sites. The multiplex fluorescent PCR detection system provided by this invention achieves effective detection of multiple methylation sites by combining capillary electrophoresis detection. Combined with corresponding detection methods and result interpretation methods, it enables highly sensitive and specific detection of colorectal cancer, possessing significant clinical application value and broad market prospects.

This invention provides a DNA methylation marker combination, kit, device, and storage medium, belonging to the field of biomedical diagnostics. It includes methylation sites in target regions of the FGGY, LMNA, REST, PLOD2, POLR1D, NFKBIZ, PRKCB, CCSER1, and NEFM genes. The target regions of the FGGY and LMNA genes are selected from Chr1, the target regions of the REST and CCSER1 genes are selected from Chr4, the target regions of the PLOD2 and NFKBIZ genes are selected from Chr3, the target region of the POLR1D gene is selected from Chr13, the target region of the PRKCB gene is selected from Chr16, and the target region of the NEFM gene is selected from Chr8. This invention is applicable to adult diffuse gliomas and offers advantages such as simplicity, economy, speed, and clinical applicability.

The application provides a DNA methylation marker cg22131907, a kit and a device for detecting type 2 diabetes, and relates to the technical field of disease diagnosis.The DNA methylation marker provided by the application has high sensitivity and strong specificity, the marker can be detected by using a Taqman probe method, and the detection is convenient, safe and easy to mass screen.The kit provided by the application comprises primer probes for detecting the methylation level of the DNA methylation site cg22131907, the incidence risk of type 2 diabetes of a subject is predicted by detecting the methylation degree of the DNA methylation site cg22131907, and basis is provided for early prediction and diagnosis of type 2 diabetes.The device provided by the application has a simple structure and can accurately realize detection on the occurrence risk of type 2 diabetes of a subject.

The present invention provides a method for determining the risk of death and / or the probability of a healthy lifespan of a dog; the method comprising a) providing a DNA methylation map from a sample obtained from the dog; and b) using the DNA methylation map to determine the risk of death and / or the probability of a healthy lifespan of the dog; wherein the DNA methylation map contains at least one methylation site as listed in Table 3.

This invention relates to a methylation site marker for assisting in the early diagnosis of esophageal squamous cell carcinoma and its application, belonging to the field of biomedical technology. The methylation site marker is one or a combination of methylation sites cg05064044, cg03395511, and cg21548813 in human peripheral blood mononuclear cells, with nucleotide sequences shown in SEQ ID NO. 1-3. This invention uses methylation chip detection to find that the methylation levels of cg05064044, cg03395511, and cg21548813 in peripheral blood mononuclear cells of esophageal squamous cell carcinoma patients were significantly higher than those in healthy controls. Further analysis revealed that the methylation levels of cg05064044, cg03395511, and cg21548813 in PBMCs of esophageal squamous cell carcinoma patients in both the training and validation cohorts were significantly higher than those in healthy controls. Finally, ROC curve analysis confirmed that the three methylation sites cg05064044, cg03395511, and cg21548813 have good specificity and sensitivity, and have high diagnostic efficacy when used alone or in combination for the diagnosis of esophageal squamous cell carcinoma. They can be used as potential molecular markers for the diagnosis of esophageal squamous cell carcinoma.

This invention discloses a gene composition, kit, and application for early diagnosis of renal cell carcinoma, relating to the field of molecular diagnostic technology. The gene composition consists of the PLIN2 gene, SLC25A25 gene, PITX1 gene, and SOX1 gene. The differential methylation site of the PLIN2 gene is cg13990947, the differential methylation site of the SLC25A25 gene is cg14294859, the differential methylation site of the PITX1 gene is cg02037307, and the differential methylation site of the SOX1 gene is cg1. 6705627; This invention, by screening four genes (PLIN2, SLC25A25, PITX1, and SOX1) and specific methylation site combinations, can accurately identify two major subtypes of renal cell carcinoma—clear cell and papillary renal cell carcinoma—compared to single-gene detection. The methylation difference between cancerous and normal tissues, Δβ-value, is greater than 0.2, solving the problem of heterogeneous renal cell carcinoma detection. The optimized urine free DNA lysis buffer and bisulfite conversion system improve the nucleic acid extraction and conversion rates. Combined with dedicated methylation-specific primers and probes, it enables non-invasive detection of urine samples.

This invention relates to the field of next-generation sequencing, specifically to a method for preparing methylated sequencing libraries. The method includes the following steps: a. pretreating a DNA sample by converting methylated cytosine (C) or unmethylated C into non-C bases; b. denaturing the nucleic acid product obtained in step a; c. ligating adapters to the denatured nucleic acid, wherein in step c, the denatured single-stranded nucleic acid is ligated with paired-end adapters. The 5' adapter includes a random sequence complementary to the 5' end of the single-stranded nucleic acid, and the 3' adapter includes a random sequence complementary to the 3' end of the single-stranded nucleic acid. In the random sequence, the content of at least one of A, T, C, and G is not higher than 24% or not lower than 26%. This invention effectively improves the library yield, quality, complexity, uniformity, methylation quantification accuracy, and methylation site detection sensitivity. Furthermore, this invention enables "one-tube" library construction, simplifying the operation, avoiding sample loss, saving costs, and shortening the library construction time.

The present application relates to a kind of artificial intelligence methylation aging clock data analysis method and system;Including: based on the coverage of single methylation site, methylation site is filtered, filter low-abundance site;For each sample, extract one or more regional features of each region;Methylation aging clock data analysis model is constructed, and the model is pre-trained on computing server;Optimal regional feature screening is carried out;Combining multiple pre-trained methylation aging clock data analysis model to obtain comprehensive model;Real-time acquisition individual data is input into comprehensive model, and real-time output variable is presented to individual reference.The present application significantly reduces the dimension of data after methylation data is filtered by site, genomic position targeted region feature extraction and optimal feature screening, retains the basic features of data, reduces the dependence of data on computing resources.

Clinically relevant cell-free (cfDNA) samples are provided for enrichment, for example, techniques for downstream analysis. For instance, cell-free DNA molecules with NCG terminal motifs can be selected because such subsets have an increased proportion of clinically relevant cfDNA. These NCG cfDNA molecules can be further selected for further enrichment based on size and / or the location of tissue-specific hypomethylation sites. As another example, cell-free DNA molecules with CGN terminal motifs can be selected because such subsets can have an increased proportion of clinically relevant cfDNA when located at tissue-specific hypermethylation sites. These CGN cfDNA molecules can be further selected based on size.

The application discloses a specific RNA-m 1 The application discloses a chain deoxyribozyme probe for specifically recognizing RNA-m 1 The application discloses a chain deoxyribozyme probe for specifically recognizing RNA-m 1 The application discloses a chain deoxyribozyme probe for specifically recognizing RNA-m

The present invention provides a method for generating a biological clock containing a DNA methylation map applicable to at least two different sample types, the method comprising: (i) providing a first set of DNA methylation maps generated from at least two different sample types from multiple subjects; (ii) generating a composite DNA methylation map from the first set of DNA methylation maps, wherein the composite DNA methylation map contains methylation sites having a matching state in the different sample types; and (iii) generating a biological clock using the composite DNA methylation map with a reference DNA methylation map from one of the at least two sample types.