142 results about "Circulating tumor DNA" patented technology

Methods and systems for targeted detection of circulating tumor DNA (ctDNA) molecules are disclosed herein. In some cases, a molecular sequencing library depleted of methylated DNA can be generated and used to detect ctDNA in a cell-free DNA sample reliably at a lower sequencing depth and lower cost than existing methods.

The present disclosure includes a method of comprising (a) obtaining cell-free DNA (cfDNA) from a sample from a subject; (b) selectively enriching subsets of the cfDNA from (a) or derivatives therefrom having one or more target regions to obtain enriched DNA, wherein the target regions are differentially methylated in cancer; (c) sequencing the enriched DNA from (b) to obtain sequence reads; and (d) partitioning a plurality of the sequence reads into two or more groups based on their methylation status and determining the fragment length distribution of the sequence reads in at least one of the groups.

The invention discloses a tiny residual focus detection method and system based on ultra-high depth sequencing, and relates to the technical field of tiny residual focus intelligent detection.The tiny residual focus detection method comprises the following steps that on the basis of a sequencing library, splitting is conducted according to a sample index to obtain a to-be-detected sample, and a consensus sequence is obtained according to a molecular identifier of the to-be-detected sample; based on a consensus sequence, filtering out the consensus sequence of which the mass value is less than 25 or the family size is less than 3, and combining a variation type and a distance from a fragment edge as noise introduced into an original nucleic acid molecular chain; a context sequence (context) and a chain direction are used as noise for introducing the capture level of PCR amplification; on the basis of the noise level, the circulating tumor DNA level is estimated in combination with tumor priori knowledge, and the MRD state is determined by detecting the significance of molecular signal sources. According to the invention, the sensitivity and specificity of MRD detection are improved.

The present disclosure relates to methods for detecting unique genetic signatures derived from markers such as, for example, mutations, somatic or germ-line, in nucleic acids obtained from biological samples. The sensitivity of the methods provides for detection of mutations associated with a disease, e.g., cancer mutations, or with inherited disease, e.g., an autosomal recessive disease, in a noninvasive manner at ultra-low proportions of sequences carrying mutations to sequences carrying normal, e.g., non-cancer sequences, or a reference sequence, e.g., a human reference genome.

The present disclosure relates to a laboratory execution system that provides for automation of laboratory processes. A centralized data management system may be dynamically updated and used to facilitate management of components of the laboratory execution system, such as an automation system and an analytics results management system that may facilitate complex analytical functions, such as synthesizing raw test data. Potential workflows include the detection of specific molecules of interest.

The invention discloses a circulating tumor DNA biosensor and a construction method and application thereof, and belongs to the technical field of biosensors. The dual-mode ratio type circulating tumor DNA biosensor comprises a sensing substrate assembled with a triangular DNA probe, a probe solution and exonuclease. The triangular DNA probe is used as an anchoring substrate to support target cycle amplification, and the sensitivity of the biosensor is effectively improved by using an ECL-RET effect and an enzyme-assisted target cycle signal amplification strategy; and the FL / ECL ratio is used as a dual-mode signal output strategy, so that the accuracy and feasibility of the detection technology are improved. The biosensor is high in accuracy, high in sensitivity and good in selectivity, quantitative detection of PIK3CA E545K ctDNA in blood of a breast cancer patient can be achieved, and the biosensor has important application value in the fields of clinical diagnosis and drug research of breast cancer.

The present disclosure relates to a laboratory execution system that provides for automation of laboratory processes. A centralized data management system may be dynamically updated and used to facilitate management of components of the laboratory execution system, such as an automation system and an analytics results management system that may facilitate complex analytical functions, such as synthesizing raw test data. Potential workflows include the detection of specific molecules of interest.

The invention relates to the technical field of biomedicine, in particular to a method for constructing a plasma ctDNA organ distribution characteristic spectrum of advanced colorectal cancer. The method comprises the following steps: collecting a peripheral blood sample at multiple time points, separating plasma by adopting a double-centrifugal method, and extracting circulating tumor DNA (Deoxyribose Nucleic Acid); carrying out whole exome sequencing based on ctDNA to obtain genome variation information and calculating variation allele frequency, and synchronously detecting the expression quantity of immune-related proteins by adopting an Olink proteomics technology; integrating the genome data, the protein expression data and the clinical pathological features, and constructing a multi-dimensional feature data matrix; and taking the organ metastasis condition confirmed by iconography as a supervision label, training a model by applying a machine learning algorithm, screening key prediction factors, constructing a quantitative prediction model, and finally generating a visual organ metastasis tendency prediction map. According to the method, early and accurate prediction of the advanced colorectal cancer organ metastasis tendency is realized through multi-omics data collaborative analysis and machine learning modeling.

The present disclosure relates to systems and methods for detecting circulating tumor DNA (ctDNA) and minimal residual disease in a patient sample..Aspects of the present disclosure relate to use of a classification module to assess whether a patient sample comprises ctDNA and minimal residual disease based, in part, on patient-specific inputs. The present disclosure is also related, at least in part, to a determination of whether a patient has cancer based on an output of the classification module.

The disclosure relates to methods of assessing the success of treatment with durvalumab and chemotherapy for resectable non-small cell lung cancer (R-NSCLC) in patients based on circulating tumor DNA (ctDNA) detection, ctDNA clearance and / or partial clearance and / or variant allele fraction (VAF) before and after such treatment. The disclosure also relates to methods for treating patients with R-NSCLC based on ctDNA detection, ctDNA clearance and / or partial molecular clearance and / or VAF before and after such treatment.

The invention discloses a high-specificity minimal residual disease (MRD) monitoring method and system based on circulating tumor DNA (ctDNA). The method comprises the following steps: receiving tumor tissue sequencing data of an UTUC patient, and generating a double-Panel target list containing personalized and fixed Panel; respectively extracting plasma cfDNA and leukocyte gDNA; performing vacuum concentration, hybrid capture and sequencing on the cfDNA library by using the double Panel lists, and performing deep sequencing on the leukocyte gDNA; constructing an individualized clonal hematopoietic mutation filtering database; actively filtering and rejecting clonal hematopoietic background mutation by utilizing a filtering database; and calculating an MRD load score based on the filtered tumor-derived mutation and outputting a report. The system comprises corresponding modules which are used for automatically executing the process. According to the invention, through cooperation of four major technologies of double-Panel design, process optimization, UMI error correction and active clonal hematopoietic filtration, MRD monitoring with extremely high sensitivity and specificity on UTUC is realized, false positive is significantly reduced, and the kit has drug resistance early warning potential.

Provided herein are methods for monitoring, identifying, assessing, circulating tumor DNA (ctDNA) for treating a subject or monitoring a subject having cancer, and related methods and uses thereof. In some embodiments, the disease or condition is a B cell lymphoma (BCL) relapsed or refractory.

The invention discloses a circulating tumor DNA (deoxyribonucleic acid) standard substance as well as a preparation method and a valuing method thereof. The preparation method comprises the following steps: (1) culturing cells; (2) cell nucleus extraction; (3) carrying out enzyme digestion on cell nucleuses; (4) purifying the fragmented DNA; (5) sampling a sample, and quantifying the sample by nanodrop measurement; (6) sampling the length of a verification fragment; and (7) mixing different ctDNAs according to the finally obtained theoretical mutation abundance of 1%, 5% and 10% to prepare the standard substance. The valuing method comprises the following steps: carrying out digital PCR amplification on a sample through a double-labeled probe to obtain the copy number concentration of a mutant gene and a wild gene or the copy number concentration of a target gene and a reference gene, and calculating the gene mutation frequency and the amplification multiple. According to the method disclosed by the invention, the fragmented DNA with the length similar to that of the ctDNA is obtained; 330bp and large fragments can be removed through two rounds of purification of a paramagnetic particle method, and a single-fragment standard substance is obtained.

Described herein are methods of preparing an enriched library of nucleic acids, comprising: (a) identifying a patient-specific panel of somatic variants present in a tumor sample from a patient, (b) generating a subset panel of somatic variants from the patient-specific panel, wherein the subset of somatic variants comprises one or more of: multi -nucleotide variants, insertions and deletions, and genomic rearrangements; (c) preparing a sample of cell-free DNA (cfDNA) fragments from the patient for sequencing; and (d) selectively enriching the cfDNA for the subset of somatic variants to generate an enriched library.

The invention relates to the technical field of biology, in particular to a cis-trans typing method for drug-resistant gene mutation EGFR T790M / C797S. The invention provides an EGFR (Epidermal Growth Factor Receptor) T790M / C797S cis-trans typing method based on a locked nucleic acid LNA (Low Nucleic Acid) probe, ultrahigh-specificity DNA (Deoxyribose Nucleic Acid) polymerase and a primer probe combination. The typing method can be used for accurately distinguishing EGFR T790M / C797S double-mutation cis-configuration and trans-configuration; meanwhile, the kit has the advantages of high sensitivity, high specificity, simple steps and low cost, is suitable for detecting low-abundance samples such as circulating tumor DNA (ctDNA) and can meet the clinical rapid detection requirement.

Provided herein are methods of determining a molecular response score for use in predictive models, including scoring based on epigenetic methylation based detection of mutant allele fraction. The molecular response score may be used to monitor and guide administration of treatment to a subject.

The invention provides a method and a system for predicting early gastric cancer prognosis by a circulating marker, and relates to the technical field of auxiliary diagnosis. The method comprises the following steps: performing multi-omics detection on a blood sample based on a preset sampling time sequence to obtain a multi-dimensional time sequence characteristic data set containing three groups of heterogeneous data of circulating tumor DNA, exosomes and protein markers; calculating a change slope and a fluctuation variance of the heterogeneous data in adjacent time sequence intervals, constructing a dynamic variation feature matrix in combination with a standard attenuation weighting factor, and deeply mining spatial cross-correlation and sequence dependence features of the matrix to generate a multi-modal fusion feature fingerprint; and performing regression operation on the feature fingerprints by using an integrated learning stack model to obtain a dynamic prognosis risk score, and further retrieving a risk hierarchical mapping table to generate a prognosis evaluation result containing a survival curve. According to the method, multi-modal heterogeneous data can be effectively fused, the biological dynamic characteristics in the tumor postoperative recovery phase are captured, and the accuracy and timeliness of early gastric cancer prognosis prediction are remarkably improved.

Disclosed herein are methods of treating an individual having cancer, of treating or identifying an individual having cancer for a treatment, or stratifying individuals having cancer for a treatment based on a tumor shed value determination in a liquid biopsy sample. Also described herein are methods of analyzing a biomarker based on a tumor shed value determination in a liquid biopsy sample.

The present invention relates to methods of treating previously untreated diffuse Large B-Cell Lymphoma (DLBCL) defined as high risk by Circulating Tumor DNA (ctDNA), by administering glofitamab and in combination with chemotherapy.

Disclosed are compositions and methods for detecting, prognosing, grading, and treating a cancer such as, for example a bladder cancer including, but not limited to upper tract urothelial carcinoma (UTUC) using circulating tumor DNA (ctDNA).

Pancreatic adenocarcinoma has the worst overall mortality of any solid tumor, with only 7% of patients surviving after 5 years. To evaluate the clinical implications of genomic alterations in this low cellularity tumor type, we deeply sequenced the genomes of 101 enriched pancreatic adenocarcinomas from patients who underwent potentially curative resections and used non-invasive approaches to examine tumor specific mutations in the circulation of these patients. These analyses revealed somatic mutations in chromatin regulating genes including MLL and ARID1A in 20% of patients that were associated with improved survival. Liquid biopsy analyses of cell free plasma DNA revealed that 43% of patients with localized disease had detectable circulating tumor DNA (ctDNA) in their blood at the time of diagnosis. Detection of ctDNA after resection predicted clinical relapse and poor outcome, and disease recurrence by ctDNA was detected 6.5 months earlier than with standard CT imaging.

Provided herein are methods for monitoring, identifying, evaluating circulating tumor DNA (ctDNA) for treating a subject or monitoring a subject having cancer, and related methods and uses thereof. In some embodiments, the disease or disorder is relapsed or refractory B-cell lymphoma (BCL).

Techniques for classifying cancers using fragmentomic features are described. An example method includes identifying data indicative of circulating tumor DNA (ctDNA) from a sample derived from a subject. The example method further includes identifying fragmentomic features based on the data. Input data, including the fragmentomic features, is input into a model configured to generate at least one probability that a tumor is within at least one category. The example method further includes generating a report based on the at least one probability that the tumor is within the at least one category.

Techniques for classifying cancers using fragmentomic features are described. An example method includes identifying data indicative of circulating tumor DNA (ctDNA) from a sample derived from a subject. The example method further includes identifying fragmentomic features based on the data. Input data, including the fragmentomic features, is input into a model configured to generate at least one probability that a tumor is within at least one category. The example method further includes generating a report based on the at least one probability that the tumor is within the at least one category.

Provided herein is a method of detecting circulating tumor DNA (ctDNA) in a sample. The method utilizes a preliminary panel that is cross-referenced with a second non-tumor sample to detect the presence or absence of any of the plurality of preliminary tumor-specific somatic mutations and removing said plurality of preliminary tumor-specific somatic mutations to obtain a patient-specific panel that can be used to detect ctDNA in further samples.

This invention relates to the field of medical technology, specifically to a method for preoperative risk assessment and prediction in liver transplant patients with hepatocellular carcinoma, comprising the following steps: Sample collection: selecting plasma samples and corresponding clinicopathological information from liver transplant recipients of hepatocellular carcinoma, and clarifying the inclusion and exclusion criteria for samples; Plasma cell-free DNA extraction and whole-genome sequencing: extracting and quality-controlling cell-free DNA from the plasma samples collected in step S1, constructing a sequencing library, and performing low-coverage whole-genome sequencing. This invention utilizes plasma-extracted cfDNA for whole-genome sequencing, combined with clinical testing information, to construct a preoperative risk assessment and prediction model for postoperative recurrence in liver transplant recipients of hepatocellular carcinoma based on non-invasive testing. This model can be used to predict the probability of recurrence-free survival before liver transplantation. The model derivation cohort integrates clinical records and circulating tumor DNA data for preoperative recurrence risk prediction.

The invention provides methods for detecting single nucleotide variants in breast cancer, bladder cancer, or colorectal cancer. Additional methods and compositions, such as reaction mixtures and solid supports comprising clonal populations of nucleic acids, are provided. For example, provided here is a method for monitoring and detection of early relapse or metastasis of breast cancer, bladder cancer, or colorectal cancer, comprising generating a set of amplicons by performing a multiplex amplification reaction on nucleic acids isolated from a sample of blood or urine or a fraction thereof from a patient who has been treated for a breast cancer, bladder cancer, or colorectal cancer, wherein each amplicon of the set of amplicons spans at least one single nucleotide variant locus of a set of patient-specific single nucleotide variant loci associated with the breast cancer, bladder cancer, or colorectal cancer; and determining the sequence of at least a segment of each amplicon of the set of amplicons that comprises a patient-specific single nucleotide variant locus, wherein detection of one or more patient-specific single nucleotide variants is indicative of early relapse or metastasis of breast cancer, bladder cancer, or colorectal cancer.

Disclosed herein are methods and systems for targeted detection of circulating tumor DNA (ctDNA) molecules. In some cases, a methylated DNA depleted molecular sequencing library can be generated and used to reliably detect ctDNA in cell-free DNA samples at lower sequencing depths and at lower costs than existing methods.

The invention relates to the technical field of lung cancer gene detection, and discloses a lung cancer gene detection method which comprises the following steps: step 1, collecting a biological sample from the body of a patient, preferentially selecting a peripheral blood sample, and controlling the sampling amount to be 5-10ml; 2, centrifuging the collected blood sample at room temperature, separating plasma and blood cells, and extracting circulating tumor DNA in the plasma by using a kit; and 3, fully diluting the extracted circulating tumor DNA to ensure that only one DNA molecule exists in each reaction unit in the digital PCR at most. According to the lung cancer gene detection method, the application and the use of the kit provided by the invention, the experimental operation process is simplified, so that an experimenter can quickly and consistently perform sample treatment, the repeatability and the standardization degree of an experiment are improved, and by accurately diluting circulating tumor DNA and performing operation by using an accurate micropipettor, the detection accuracy is improved. And the accuracy and the reliability of the experiment are ensured.

Methods and systems for targeted detection of circulating tumor DNA (ctDNA) molecules are disclosed herein. A cell-free nucleic acid may be subjected to conditions to increase its methylation level, thereby yielding a hypermethylated cell-free nucleic acid, and subsequently identifying a sequence of the hypermethylated cell-free nucleic acid.