152 results about "Liquid biopsy" patented technology

The invention relates to a breast cancer plasma transporter miRNA marker and application thereof, and belongs to the technical field of biological detection. In the prior art, biomarkers for breast cancer liquid biopsy have the problems of low content, high heterogeneity, insufficient time resolution and the like, so that the detection reliability is limited. According to the invention, a specific miRNA (micro Ribonucleic Acid) marker (including one or more of let-7d-5p, miR-103a-3p and miR-22-3p) of the plasma transporter is provided. The marker can be used for preparing a breast cancer detection reagent or kit. Clinical verifications show that the miRNAs are remarkably and highly expressed in plasma migrators of breast cancer patients, the AUC value reaches 0.763-0.808, the sensitivity is 66.7%-86.7%, the specificity is 66.7%-88.3%, the miRNAs have the advantages of high signal-to-noise ratio and dynamic monitoring, and the accuracy and practicability of breast cancer detection are remarkably improved.

Methods, systems, and software for estimating circulating tumor fraction are provided. A first plurality of nucleic acid sequences for a plurality of loci in genomic DNA from a solid tumor sample is obtained. A second plurality of nucleic acid sequences for a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the same subject is obtained. One or more somatic mutations is identified in the first plurality of nucleic acid sequences. A variant allele frequency (VAF) is determined for each somatic mutation based on a frequency of the respective somatic mutation in the liquid biopsy sample and a frequency of the corresponding wild type allele in the liquid biopsy sample, thereby determining a set of VAFs. An estimate of the circulating tumor fraction for the test subject is determined based on the set of VAFs for the one or more somatic mutations.

The invention discloses a preparation method and application of a photo-thermal biosensor for tumor cell quantification and vitality dual-index liquid biopsy. Phosphatidylserine (PS) is exposed by enriching and cracking tumor cells, is identified and combined by an aptamer Apt2, and is driven to be separated from Apt2-Cu2-xTe NSs; after magnetic separation, separated supernatant is subjected to photo-thermal detection; the photo-thermal signal intensity is positively correlated with the number of cells, so that quantitative detection is realized; during cell apoptosis, PS is turned out of the membrane, Apt2-Cu2-xTe NSs is combined with the surface of the membrane, separated supernatant is subjected to photo-thermal detection after magnetic separation, and the photo-thermal signal enhancement amplitude is in negative correlation with cell activity. The platform has the advantages of POCT characteristics, low cost and portability, and a new tool is provided for precise tumor diagnosis and treatment.

The invention discloses an esophageal adenocarcinoma plasma circulation microbial marker combination, a reagent, a kit, a risk prediction model and application thereof, and belongs to the cross technical field of liquid biopsy and microbiomics. The esophageal adenocarcinoma plasma circulating microbial marker combination disclosed by the invention comprises enterobacteriaceae, cilia, prevotella, ackermania, lactobacillus fermentum and streptococcus. When the esophageal adenocarcinoma plasma circulating microbial marker combination is used for verifying esophageal adenocarcinoma patients and healthy controls, the AUC is 0.952, the sensitivity is 100%, the specificity is 80.00%, the accuracy is 91.43%, the positive predictive value is 86.96%, and the negative predictive value is 100%; the esophageal adenocarcinoma plasma circulating microbial marker combination can effectively distinguish esophageal adenocarcinoma patients from healthy people, is suitable for early screening of esophageal adenocarcinoma, and has remarkable clinical screening application value.

The invention discloses a single cell activity evaluation method based on cell nucleus geometric parameters and a Bayesian framework, which comprises the following steps: establishing a HeLa cell activity gradient model through adriamycin induction, carrying out cell nucleus segmentation by adopting Cell pose 3.0 and extracting 26 geometric features, screening a high-confidence sample in combination with a Bayesian deep learning framework, and evaluating the activity of a single cell according to the high-confidence sample. And constructing a multi-modal feature fusion model to integrate geometric features and deep semantic features, and finally realizing unmarked and high-precision single cell activity evaluation. The method overcomes the limitation that a traditional technology depends on biochemical markers, has the advantages of being easy and convenient to operate, high in flux and high in interpretability, and provides an innovative technical means for tumor liquid biopsy and precise medical treatment.

The application discloses an exosome small non-coding RNA molecule marker and application thereof, and belongs to the field of tumor liquid biopsy and molecular diagnosis. The exosome small non-coding RNA molecule marker is at least one of tRNA-GlyGCC-5 and sRESE; the nucleotide sequence of the tRNA-GlyGCC-5 is shown as SEQ ID NO:1; and the nucleotide sequence of the sRESE is shown as SEQ ID NO:2. The sRESE in the application is a brand new small non-coding RNA sequence, and is first discovered by the inventor, which is important for the marker of esophageal cancer and the research on disease progression mechanism. The tumor diagnosis kit provided by the application, which comprises the exosome small non-coding RNA molecule marker, is a liquid diagnosis monitoring kit with non-invasiveness, high sensitivity, high specificity and applicability to general survey or screening.

The invention discloses an early-stage lung cancer prediction method based on a multi-modal eccDNA marker, and relates to the technical field of liquid biopsy, and the method comprises the following steps: collecting a peripheral blood sample, carrying out differential centrifugal separation on plasma, constructing a cfDNA library, and carrying out double-end sequencing to obtain original sequencing data; extracting structural features through an eccDNA model, and inputting the structural features into a first machine learning model to generate a circular DNA score; extracting variation features through an SNV model, and inputting the variation features into a second machine learning model to generate a spectrum feature score; extracting copy number features through a CNV model, and inputting the copy number features into a third machine learning model to generate copy number scores; carrying out probability distribution calibration on the circular DNA score, the spectrum feature score and the copy number score; inputting the three types of molecular features into a deep neural network to generate a first fusion score; inputting the calibrated score into a logistic regression model to generate a second fusion score; and generating a final lung cancer risk probability according to the first fusion score and the second fusion score.

Described here are methods to utilize genomic and epigenomic detection platforms to provide quantitative metrics, including those representative of molecular phenotypes, in a variety of iimmuno-oncology applications, including those related to the characterization of patient responsiveness, treatment efficacy, adverse events among otheres. In various embodiments, described herein is an example of generating prognostic and t outcomes of a cfDNA-derived promoter methylation score in predicting ICI benefit.

The invention discloses a postoperative recurrence monitoring system and method for bile liquid biopsy, and relates to the technical field of medical detection, and the method comprises the following steps: obtaining medication data, bile liquid data and gene data of a target object; preprocessing the medication data and the bile liquid data to generate a sampling interference index sequence, and further performing weighted fusion on the gene data by the sampling interference index sequence to obtain a mutation load index of each gene detection time point; and within the time sequence range of the gene data, performing sliding window analysis on the sampling interference index sequence to generate an abnormal chain marker sequence. According to the method, the time sequence mismatch degree is accurately quantified by constructing a time difference matrix, and a weight distribution mechanism is dynamically adjusted in combination with medication volatility, so that the generation process of the sampling interference index can adaptively reflect the influence of medication mode change on the sampling quality; the problem of interference evaluation deviation caused by mismatching of medication data and bile sampling time is effectively solved.

The invention belongs to the technical field of biological medicine, and particularly relates to application of actinomycin D in preparation of a ctDNA detection sensitizer. The invention provides a ctDNA release method based on actinomycin D as an enhancer, which can significantly improve the release level of ctDNA in early small-volume tumors and tiny residual lesions, thereby improving the sensitivity and positive detection rate of liquid biopsy in MRD detection. Under an extremely low dosage, the ActD can generally promote a plurality of human tumor cells to release ctDNA under the condition of not causing obvious cell death, and has good biological safety and adaptability. The method is especially suitable for tiny, biological inert or anatomical position hidden focuses which are difficult to identify by iconography, namely blind area patient groups in disease monitoring, and has a wide clinical application prospect.

The invention specifically discloses application of VGF as a diagnostic biomarker for prostatic cancer, and relates to the technical field of biological medicines. The secretory protein VGF is identified to be remarkably up-regulated in prostatic fluid of a prostatic cancer patient before puncture for the first time, high expression of the secretory protein VGF is proved to be independently related to shorter progression-free lifetime and total lifetime through a public database, and a brand-new liquid biopsy marker is provided for PCa non-invasive early screening and prognosis evaluation.

The application provides a kind of nanoparticle, preparation method and its early screening related application of cancer, wherein, nanoparticle includes superparamagnetic nanometer core, cationic polymer modified on the surface of superparamagnetic nanometer core and targeted polypeptide grafted on cationic polymer, the targeted polypeptide can specifically recognize tumor specific antigen protein, and has the modular structure of rigid helix and charge repulsion sequence.The plasma low-abundance protein enrichment nanoparticle provided by the application can be used for the detection of early screening of tumor through liquid biopsy, can significantly improve the detection rate of early tumor, and has important clinical significance.

The invention provides an EGFR-TKI drug-resistant biomarker detection method based on a non-immobilized GO-SELEX screening aptamer and a kit. In the preparation process of the kit, a nucleic acid aptamer Osi-1 capable of being specifically combined with characteristic protein (Calnexin) in EGFR-TKI drug-resistant cell supernatant is obtained through a GO-SELEX technology. Furthermore, an unmarked optical sensing platform is constructed in combination with gold nanoparticles, so that rapid and sensitive detection of Calnexin is realized. The kit is suitable for early recognition of EGFR-TKI drug resistance, and can be used for clinical liquid biopsy and precise treatment monitoring.

The application discloses a free DNA methylation and fragmentomics combined analysis method based on targeted CpG bisulfite sequencing, and belongs to the technical field of liquid biopsy and epigenetic detection. The application extracts cfDNA from blood plasma, carries out high-throughput sequencing after library construction by a methylation adapter, bisulfite conversion, and biotin probe targeted capture of a CpG enrichment region, and simultaneously realizes single-base resolution methylation accurate quantification and FRAGMA fragmentomics analysis by using the same sequencing data, so that the accuracy of methylation quantification results is inferred, and the optimal detection region is iteratively selected; multi-dimensional characteristics such as a methylation ratio, an 11nt cutting map, a CGN / NCG motif ratio and a fragment length distribution are fused to construct a machine learning / deep learning model to output a unified disease risk score. The application realizes the bimodal integration of methylation chemical signals and fragmentomics structural signals in a targeted sequencing system for the first time, and has the advantages of low cost, high sensitivity and strong clinical adaptability.

An imaging structure identification system includes an optical imaging system configured to illuminate a liquid biopsy sample for a subject. The liquid biopsy sample has one or more biological structures that are labeled with one or more fluorophores associated with a fluorescence assay for a disease state allowing detection of emitted electromagnetic radiation from the liquid biopsy sample as image data. The system also includes a processing system configured to identifying the subject as being at reduced risk for having the disease state if the subject profile is similar to the first predetermined profile for subjects not being in the disease state. However, if the subject profile is not similar to the first predetermined profile for subjects not being in the disease state it is not determinative if the subject is in the disease state.

The invention describes a novel nanoparticle coated with a Hypericum perforatum extract and a novel diagnostic kit in which such nanoparticle is used and isolates cancer cells, achieving the effective, accurate and efficient diagnosis and prognosis of different types of cancer, by use of samples from liquid biopsies.

Compositions and methods are provided for determining the presence of early-stage osteoarthritis (OA) in an individual by single cell profiling of a blood sample. Through use of machine learning, it is shown that immune cell features associated with OA are present and detectable in the early stages of OA and can be utilized for early detection of the disease.

To provide methods and systems for tumor informed circulating tumor fraction estimation.SOLUTION: Methods, systems, and software for estimating circulating tumor fraction are provided. A first plurality of nucleic acid sequences for a plurality of loci in genomic DNA from a solid tumor sample is obtained. A second plurality of nucleic acid sequences for a plurality of cell-free DNA fragments obtained from a liquid biopsy sample from the same subject is obtained. One or more somatic mutations is identified in the first plurality of nucleic acid sequences. A variant allele frequency (VAF) for each somatic mutation is determined based on a frequency of the respective somatic mutation in the liquid biopsy sample and a frequency of the corresponding wild type allele in the liquid biopsy sample, thereby determining a set of VAFs. An estimate of the circulating tumor fraction for the subject is determined based on the set of VAFs for the one or more somatic mutations.SELECTED DRAWING: Figure 1A

A method for analysing chromosome interactions relating to canine cancer wherein the chromosome interactions relate to either a class of cancer or a specific cancer. The invention allows use of a liquid biopsy method.

The application relates to the technical field of biological medicine, and discloses a tumor marker micro-detection and analysis method based on liquid biopsy. The method comprises the following steps: extracting peripheral blood free DNA and performing double-end sequencing; jointly extracting multi-dimensional features such as ctDNA fragment length distribution, end sequence preference, nucleosome positioning signal and CpG methylation state from the sequencing data; constructing a feature matrix under unified genomic coordinates through space-time alignment; inputting a pre-trained cross-scale graph neural network model, taking a genomic region as a node and physical and functional proximity as an edge, learning a coupling mode of multi-modal features in a local chromatin structure, and outputting a malignant risk score; and combining a threshold to distinguish early lung cancer and benign and malignant nodules. The application comprises corresponding functional units and supports efficient parallel analysis. The system significantly improves detection sensitivity and specificity, reduces the false negative rate by 36%, and realizes non-invasive and accurate early lung cancer screening.

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.

This utility model discloses a liquid biopsy kit, belonging to the field of medical reagent storage technology. The device includes a box with an openable cover at the top and support legs at the bottom. Inside, there is a pull-out placement plate with multiple slots for different reagent tube sizes. The rear of the box has a storage compartment with a cooling mechanism, which cools the reagent tubes through a ventilation structure. The bottom of the box has a buffer plate, and each placement slot has an independent buffer pad to effectively improve placement stability. The inside of the cover has a storage compartment and elastic pads to cushion impacts in case of drops, preventing damage to the reagent tubes. This utility model has a compact structure, high storage safety, strong adaptability, and is easy to clean and maintain. It is suitable for the cold storage and transportation management of liquid samples.

The invention belongs to the technical field of nano preparations, and particularly relates to a preparation method and application of extracellular vesicles of tissue interstitial fluid. The extracellular vesicles of the tissue interstitial fluid are prepared by combining collagenase II and amylase, the prepared extracellular vesicles of the tissue interstitial fluid are high in yield and good in quality, and the extracellular vesicles can be used for tissue repair and regeneration, tissue microenvironment research, liquid biopsy or preparation of engineered extracellular vesicles for preventing or treating inflammatory diseases.

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 invention provides a nanoparticle, a preparation method and a cancer early screening related application thereof, the nanoparticle comprises a superparamagnetic nano core, a cationic polymer modified on the surface of the superparamagnetic nano core and a targeting polypeptide grafted on the cationic polymer, the targeting polypeptide can specifically recognize a tumor specific antigen protein, and has a modular structure comprising a rigid helix and a charge repulsion sequence. The plasma low-abundance protein-enriched nanoparticles provided by the invention can be used for early screening detection of tumors through liquid biopsy, can significantly improve the detection rate of early tumors, and have important clinical significance.

Provided is a method for determining the likelihood of the onset of IgA nephropathy or the activity of the IgA nephropathy by means of a liquid biopsy of blood other than a highly invasive kidney biopsy or conventionally used proteinuria or hematuria. The present invention is a method for determining the likelihood of the onset of IgA nephropathy or the activity of the disease in a subject animal, said method comprising the steps of: (a) measuring an IgA nephropathy marker protein contained in an IgA immune complex in a blood sample collected from the subject animal; and (b) determining the likelihood of the onset or the activity of the IgA nephropathy in the test animal on the basis of the amount of the IgA nephropathy marker protein, which is a protein contained in an IgA immune complex, measured in the step (a), the IgA nephropathy marker protein being a protein contained in an IgA immune complex, and the IgA nephropathy marker protein being a protein contained in an IgA immune complex. The content of the IgA immune complex in the group of IgA nephropathy patients is greater than the content of the IgA immune complex in the group of healthy persons.

The invention belongs to the technical field of medicine, and discloses an application method of tumor-killing effect B cells in colorectal cancer liver metastasis, Meta-CBL is used for transforming the B cells into tumor-killing effect cells for the first time, and the anti-tumor immune effect is remarkably enhanced. In a tumor microenvironment, the meta-CBL can directly kill tumor cells and activate other effector immune cells, so that synergistic anti-tumor is realized. By combining liquid biopsy and single cell sequencing, tumor load and microenvironment immune state can be tracked in real time. The evaluation precision is higher than that of traditional iconography, invalid treatment patients can be recognized in the early stage, and the treatment strategy is adjusted in time. Precise treatment and dynamic prognosis evaluation of colorectal cancer liver metastasis are realized by innovatively utilizing meta-CBL, and the defects of limited treatment effect and lagging evaluation means in the prior art are overcome. The comprehensive system structure and the precise treatment strategy of the system bring brand new treatment choices and remarkable survival benefits for patients with colorectal cancer liver metastasis, and the system has extremely high industrialization and clinical popularization value.

This invention discloses a method and system for assessing tumor content in liquid biopsies. The method performs quality control on high-throughput sequencing data from body fluid samples, filtering germline variations, clonal hematopoietic-related variations, and sequencing errors to obtain copy number variation (CNV) information and somatic mutation characteristic information. A weighted mean squared error loss function is constructed based on the CNV information, and the tumor content is solved using a constrained gradient descent method. When the CNV signal does not meet preset judgment conditions, the system switches to the mutation characteristic module, constructing a negative log-likelihood function based on a binomial distribution based on the principal clonal cluster, and solving for the tumor content through iterative optimization. In extreme cases, a backoff mechanism is triggered. This invention combines the stability of CNV at high tumor content with the sensitivity of mutational VAF at low content, achieving adaptive assessment from low to high tumor content.

Described herein are gene features for providing prognosis, diagnosis, treatment and molecular subtype classification of cancer by genomic and epigenomic profiling, methods and compositions for determining cancer and subtypes, including breast cancer, and provide specific and sensitive detection of biomarkers of interest. Such biomarkers indicate disease pathogenesis, which provides opportunities to select treatment, including treatment regimens intended to identify responsive candidates and overcome resistance mechanisms.

The invention provides a digestive tract tumor course monitoring system. The system comprises a system control module, a first-stage detection module, a second-stage detection module, a third-stage detection module, a risk assessment module and an intervention decision module. The primary detection module is used for collecting tumor markers, images and clinical symptom data of a patient; the second-stage detection module is used for performing liquid biopsy, pathological biopsy and metabolic function evaluation on the first-stage positive patient; the third-stage detection module is used for carrying out micro-metastasis detection and immune microenvironment and genome analysis on a second-stage positive patient; the risk assessment module determines a patient risk level based on a detection result; the intervention decision module outputs intervention measures based on the risk level; the system control module manages and coordinates operation of all the modules. Each detection module automatically captures detection data by being connected with a hospital system, and judges an abnormal condition according to a set threshold value. According to the system, through a logic mechanism of grading detection and grading intervention, precise monitoring and early warning intervention on the disease course of the digestive tract tumor patient are realized.