45 results about "Aneuploidy" patented technology

The present invention addresses the problem of specifically clarifying the effects on a fertilized egg when 5-ALA is administered to a human female suffering from infertility, and constructing a more effective means for treating infertility through the suppression of chromosomal abnormalities. It has been confirmed that, when 5-ALA is ingested in combination with a drug therapy that is generally performed in the treatment of female infertility, the rate of chromosome aneuploidy in a fertilized egg or the like is significantly reduced, and the qualitative improvement of an embryo through improvement of the stability of the chromosomes is expected.

The invention provides methods for determining aneuploidy and / or fetal fraction in maternal samples comprising fetal and maternal ctDNA by massively parallel sequencing. The method comprises a novel protocol for preparing sequencing libraries that unexpectedly improves the quality of library DNA while expediting the process of analysis of samples for prenatal diagnoses.

This document provides methods and materials for assessing and / or treating subjects (e.g., humans) suspected of having cancer. For example, this document provides methods and materials for a nucleic acid sequence analysis which can determine a sequence of B cell receptor. In some cases, determining a sequence of B cell receptor (and, optionally, identifying the presence of one or more mutations and / or identifying the presence of aneuploidy) in DNA (e.g., cell-free DNA (cfDNA)) in a fluid sample (e.g., a cerebrospinal fluid sample) obtained from a subject (e.g., a human subject such as a human suspected of having cancer) can be used to identify the subject as having cancer.

The invention belongs to the technical field of biological information detection, provides a genetic detection method, system, product and equipment before embryo implantation, and aims to solve the problems that a conventional genetic detection process before embryo implantation is complicated, depends on a complete family sample, is difficult to distinguish equilibrium translocation and unbalanced translocation, is low in linkage analysis efficiency, needs to independently detect items and the like. According to the method provided by the invention, parent haplotypes can be constructed on the basis of monomolecular length reading sequencing data of male parents, female parents and to-be-implanted embryo samples in families, sequence similarity is analyzed on the basis of the parent haplotypes, and the to-be-implanted embryo samples can be obtained by tracing genetic sources of the haplotypes of the to-be-implanted embryo samples. And determining whether the to-be-implanted embryo carries the single-gene genetic disease and / or chromosome structure rearrangement or not. According to the method, integrated detection of aneuploidy, monogenic hereditary diseases and chromosome structure rearrangement before embryo implantation can be completed on a single platform, and whether the embryo to be implanted has genetic defects or not can be quickly, simply, efficiently and accurately judged in a one-stop manner.

An Artificial Intelligence (AI) based computational system is used to non-invasively estimate the presence of a range of aneuploidies and mosaicism in an image of embryo prior to implantation. Aneuploidies and mosaicism with similar risks of adverse outcomes are grouped and training images are labelled with their group. Separate AI models are trained for each group using the same training dataset and the separate models are then combined, such as by using an Ensemble or Distillation approach to develop a model that can identify a wide range of aneuploidy and mosaicism risks. The AI model for a group is generated by training multiple models including binary models, hierarchical layered models and a multi-class model. In particular the hierarchical layered models are generated by assigning quality labels to images. At each layer the training set is partitioned in the best quality images and other images. The model at that layer is trained on the best quality images, and the other images are passed down to the next layer and the process repeated (so the remaining images are separated into next best quality images and other images). The final model can then be used to non-invasively identify aneuploidy and mosaicism and associated risk of adverse outcomes from an image of an embryo prior to implantation.

The present application belongs to the technical field of biological information detection, and provides a pre-implantation genetic diagnosis method, system, product and equipment. The present application is aimed at the problems of complex traditional pre-implantation genetic diagnosis process, dependence on complete family sample, difficulty in distinguishing balanced translocation and unbalanced translocation, low linkage analysis efficiency, and the need for independent detection, etc. The method provided by the present application can be based on single molecule long read sequencing data of the paternal sample, the maternal sample and the to-be-implanted embryo sample in the family, construct the parental haplotype, and analyze the sequence similarity based on the same. By tracing the genetic source of the haplotype of the to-be-implanted embryo sample, it is determined whether the to-be-implanted embryo carries a monogenic genetic disease and / or a chromosome structure rearrangement. The present application can complete the integrated detection of pre-implantation aneuploidy, monogenic genetic disease and chromosome structure rearrangement on a single platform, and quickly, simply, efficiently and accurately determine whether the to-be-implanted embryo has genetic defects.

Methods of identifying genetic mutations and / or genetic alterations are provided.SOLUTION: Methods for classifying the presence or absence of genetic mosaicism for a copy number variation in one or more fetuses (e.g., predicting whether a fetus or more than one fetus is affected by a copy number variation) are provided. The sample nucleic acid is subjected to a sequencing process and the resulting sequence reads are analyzed to identify genetic copy number variation regions. Genetic mosaicism for a copy number variation region is classified for a fetus or more than one fetus based on (i) a mosaicism ratio of a fraction of nucleic acid having the copy number variation region to a fraction of fetal nucleic acid and (ii) a chromosome having the genetic copy number variation region (e.g., an identified type of aneuploidy) or (ii) a number of fetuses carried by a pregnant female.SELECTED DRAWING: None

A method for detecting chromosome aneuploidy of a fetus on the basis of synthetic data, and a computer-readable medium for recording a program applied to perform the method are provided. According to exemplary embodiments, non-invasive prenatal diagnosis of chromosome aneuploidy in a fetus can be performed with excellent sensitivity and specificity.

The application discloses a detection system, device and method for embryo chromosomal aneuploidy and parent contamination analysis. The system comprises a database module, an alignment module, an analysis and calculation module and a parent contamination detection module. The analysis and calculation module is used for performing the following steps: calculating the ratio of the number of effective sequences matched to each chromosome to the number of corresponding chromosome sequences in the reference database, performing statistical analysis, obtaining the number of target chromosomes of the sample to be detected, and obtaining the detection result of whether the frequency of alleles observed in the genetic linkage disequilibrium mode is abnormal. The parent contamination detection module comprises a contamination prediction model. The aneuploidy detection and parent contamination analysis of the embryo can be simultaneously realized by one detection.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

The invention belongs to the technical field of assisted reproduction, and particularly relates to a biological response type memristor for in-vitro embryo monitoring and application of the biological response type memristor. The memristor comprises a substrate, a bottom electrode, a dielectric layer and a top electrode which are sequentially arranged from bottom to top, the dielectric layer is a double-layer functional layer composed of an Nb2O5 thin film and a barium titanate thin film, the barium titanate thin film is located on the upper layer of the bottom electrode, and the Nb2O5 thin film is located on the upper layer of the barium titanate thin film. The memristor realizes response to biological information by monitoring metabolic byproducts and oxidative stress markers in an embryo in-vitro culture solution in real time, realizes operation by inducing redistribution of surface charges of an interface through ion adsorption, and shows a resistance state transformation characteristic. Besides, the system breaks through the limitation of traditional microscope visual evaluation, realizes direct, sensitive and quantitative electric signal reading of the embryo metabolism state and the oxidative stress level, and solves the problem of embryo development potential evaluation caused by the increase of aneuploid rate in old lying-in women and recurrent implantation failure groups.

The invention belongs to the field of genetics detection, and particularly relates to a genetics-integrated single-molecule sequencing detection kit and system before embryo implantation. Specifically, the kit and the system provided by the invention can realize synchronous detection of human pre-implantation embryo aneuploid, copy number variation, chromosome structure abnormality and monogenic diseases. According to the method, the parent sample and the embryo sample are subjected to single molecule length reading sequencing, family members except a certificate and parents are not needed, direct detection of aneuploidy, copy number variation, chromosome structure abnormality and the like and indirect detection based on haplotype inference are achieved, the detection result is accurate, sensitive and visual, and information is comprehensive. According to the kit and the system disclosed by the invention, only the same experimental system and the same single-molecule long-fragment sequencing platform are needed, so that PGT-A, PGT-M, PGT-SR and haplotype genetic condition detection can be completely supported, the process is simple and convenient, the application range is wide, and therefore, the kit and the system have a good practical application value.

The invention provides methods for determining aneuploidy and / or fetal fraction in maternal samples comprising fetal and maternal cfDNA by massively parallel sequencing. The method comprises a novel protocol for preparing sequencing libraries that unexpectedly improves the quality of library DNA while expediting the process of analysis of samples for prenatal diagnoses.

The invention relates to the technical field of biological information processing, in particular to a cattle embryo pre-implantation genetic evaluation method and system based on whole genome sequencing, and the method comprises the following steps: obtaining whole genome sequencing data of a male parent and a female parent, embryo trophoblast live detection sequencing data and culture solution free desoxyribonucleic acid sequencing data; performing variation detection and haplotype phasing on male and female parent data to form haplotype data, and calculating a haplotype transmission posterior at an anchor point based on trophoblast data; performing genome segmentation based on reading depth observation and allele frequency observation of a trophoblast and a culture solution, and performing Bayesian inference by combining haplotype transfer posteriori as priori to obtain posteriori probabilities of aneuploid, copy number variation, chimera, pathogenic homozygosis and pollution events; and outputting a passing / rechecking / elimination conclusion, adding sequencing and updating the posteriori during rechecking until ending, and outputting a final conclusion and a genome breeding value, so that the evaluation reliability and the decision interpretability are improved.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

To provide a method for identifying the presence of aneuploidy in the genome of a mammal.SOLUTION: Amplifying a plurality of chromosomal sequences in a cell-free DNA sample with a single primer pair complementary to the chromosomal sequences, wherein the primer pair amplifies a unique amplicon comprising short interspersed repeat sequences, determining at least a portion of the nucleic acid sequence of the plurality of amplicons to produce amplicon sequences, mapping the amplicon sequences to a reference genome, dividing the amplicon sequences into a plurality of genomic intervals, quantifying the number of reads for amplicon sequences mapped to the genomic intervals, and comparing the number of reads of amplicon sequences within a first genomic interval to: Comparing the number of reads of amplicon sequences in the one or more different genomic intervals, thereby identifying the presence of an aneuploidy in the genome of the mammal.SELECTED DRAWING: None

The application provides a non-invasive prenatal fetal chromosome detection device, which enriches fetal free DNA in the plasma of a pregnant woman to be detected through a magnetic bead purification method, obtains a free DNA sample to be detected, improves the fetal free DNA concentration proportion in the sample to be detected, can realize automatic detection of the free DNA sample to be detected, reduces the occurrence of detection failure or false negative results, performs chromosome detection based on a negative Z value and a positive Z value corresponding to the chromosome to be detected, can effectively improve the accuracy and comprehensiveness of fetal chromosome detection, covers non-euploid abnormality detection of 23 pairs of chromosomes, improves the sensitivity and specificity of chromosome detection, provides stronger technical support for prenatal screening, and can be widely applied to the technical field of chromosome detection.

The present application provides a kind of embryo relationship determination method, device, computer equipment, storage medium and program product, the method comprises: embryo is carried out before embryo implantation aneuploid gene detection shallow sequencing, obtains embryo sequencing FASTQ data;The FASTQ data of embryo sequencing is mixed, and the FASTQ file of each pair of sample is obtained;The FASTQ file of each pair of sample is preprocessed, and single nucleotide polymorphism site information is obtained;The likelihood ratio of sibling relationship is calculated using single nucleotide polymorphism site information.The method can be realized in the scene of shallow sequencing, the likelihood ratio of sibling relationship is calculated to determine the relationship of embryo, the method can accurately determine the relationship of brother and sister of embryo, assist medical staff to select correct embryo, the method is also applicable to the relationship of embryo and parent determination.

Controls for the identification of various genotypes and / or for the identification or characterization of a disease or condition are described. These controls can be especially useful for diagnostic tests that use circulating cell-free DNA or microRNA. A control may consist of a mixture of nucleic acids. In some formulations, a control comprises liposomes, for example, where the nucleic acids of the control are associated with the liposomes. For example, controls are useful for determining whether a fetus has aneuploidy. Methods for using these controls are also described.

Disclosed herein is a system and method for increasing the fidelity of measured genetic data, for making allele calls, and for determining the state of aneuploidy, in one or a small set of cells, or from fragmentary DNA, where a limited quantity of genetic data is available. Poorly or incorrectly measured base pairs, missing alleles and missing regions are reconstructed using expected similarities between the target genome and the genome of genetically related individuals. In accordance with one embodiment, incomplete genetic data from an embryonic cell are reconstructed at a plurality of loci using the more complete genetic data from a larger sample of diploid cells from one or both parents, with or without haploid genetic data from one or both parents. In another embodiment, the chromosome copy number can be determined from the measured genetic data, with or without genetic information from one or both parents.

During aging, egg cells exhibit gradual loss of adherin complexes. The absence of connexin ultimately results in premature separation of sister staining monomers, resulting in aneuploidy. The inventors have designed an artificial adhesion system that binds staining monomers or chromosomes by forming complexes, thereby reducing the phenomena of premature separation of age-related sister staining monomers, e.g., in egg cells. The artificial adhesion system is a complex, and the aneuploidy risk is reduced by binding chromosomes or dyeing monomers. The complex comprises (I) one or more first proteins and (II) one or more second proteins wherein: (I) the first protein and (II) the second protein each comprise (i) a chromatin binding component, (ii) a protein binding region located at the N-terminus of the chromatin binding component, (Hi) a protein binding region located at the C-terminus of the chromatin binding component. The invention also includes nucleic acid molecules encoding the complexes. In addition, several in vitro methods associated with the complexes or nucleic acid molecules encoding said complexes also constitute part of the invention.

This invention provides a method for single-cell reduced-representation bifulfite sequencing (scRRBS) of embryo culture medium. Using medical waste (blastocyst culture medium) from in vitro fertilization (IVF) procedures as raw material, this invention allows for simultaneous dual analysis of embryonic chromosomal aneuploidy and DNA methylation status. It assesses embryonic developmental potential from a novel perspective, considering epigenetics and the embryo's response to its culture environment, providing a new reference for selecting the "right" embryos in assisted reproduction and strongly supporting improvements in the success rate of IVF cycles.

In an embryo culture dish that includes a plurality of wells that each contain an embryo together with a culture solution, the plurality of wells are disposed independently and adjacently at a bottom part of the embryo culture dish, a recess part that can retain the culture solution together with the well is formed per well at the bottom part independently from another recess part, a movement block part that permits circulation of the culture solution and blocks movement of the embryo is provided between the well and the recess part, and a volume of the recess part is equal to or more than a volume of a culture solution to be sucked up for testing for aneuploidy of a chromosome of the embryo cultured in the well. By so doing, it is possible to suck up the culture solution for testing for aneuploidy of chromosomes of an embryo to be cultured, and dispose the wells close to each other that contain a plurality of embryos.

The present application relates to the assisted evaluation method of the second biopsy in the pre-implantation genetic testing. The blastocyst first biopsy process collects and cryopreserves the corresponding biopsy droplet; for the blastocyst with CNV detection failure or suspected abnormal CNV detection result in the first biopsy cell, the first biopsy droplet is thawed to complete genome amplification, CNV library construction, high-throughput sequencing and CNV analysis, and the second biopsy suggestion is given according to the detection result. If the biopsy droplet detects the abnormal aneuploidy or chimera clinically interpreted, it is suggested that the corresponding blastocyst has a high probability of chromosomal abnormality, and the second biopsy is not recommended; if the biopsy droplet does not detect the abnormal aneuploidy or chimera clinically interpreted, it is suggested that the corresponding blastocyst has a high probability of chromosomal normality, and the second biopsy is recommended. The present application proves that the first biopsy droplet contains detectable genetic material, and the consistency of the chromosomal ploidy detection result and the biopsy cell is more than 80%, which can assist the second biopsy decision and improve the decision efficiency and scientificity of PGT detection.

The present application relates to the technical field of biomedical detection, and in particular to a method for constructing a screening model for fetal chromosomal aneuploidy, a feature combination and a detection method. The method for constructing the screening model comprises: performing low-depth whole genome sequencing on cfDNA of a maternal plasma sample, analyzing 5' end base motif frequency and 15Mb sliding window coverage of the cfDNA; screening cfDNA features that have significant differences between a true positive group and a healthy control group and have no differences between a false positive group and the healthy control group; and constructing the screening model by machine learning using maternal age, Z value and the screened cfDNA features. The present application also provides a feature combination comprising 5' end base motif frequencies of GAGC, GAGG, TATT and TAGG, cfDNA coverage of regions of chr18:30000000-45000000, chr18:60000000-75000000, chr21:30000000-45000000 and chr21:45000000-46709983, and a Z value and maternal age. The present application can effectively reduce the false positive rate of fetal chromosomal aneuploidy screening.

Disclosed herein are agents, compositions and methods for increasing the developmental potential of human preimplantation embryos. Disclosed herein are methods of reducing or decreasing replication abnormalities and / or aneuploidies in an embryo as well as increasing genome stability and / or developmental potential of an embryo by activating kinases and / or their signaling pathway in an oocyte including but not limited to ATR, WEE1, and CHK1. Also disclosed herein are methods of reducing or decreasing replication abnormalities and / or aneuploidies in an embryo as well as increasing genome stability and / or developmental potential of an embryo using polynucleotides, polypeptides and / or agents which increase efficiency of the "fork reversion and repair" pathway and / or decrease detrimental outcomes such as fork collapse, tranlesion synthesis and / or gap formation. Lastly disclosed herein are methods of reducing or decreasing replication abnormalities and / or aneuploidies in an embryo as well as increasing genome stability and / or developmental potential of an embryo using one or more polynucleotides or polypeptides including but not limited to CHEK1, WEE1, ETAA1, ATRX, BLM, BRCA2, CHD4, DNA2 (DNA2L), EXO1, FANCC, FANCG, FBH1 (FBXO18), HLTF (SMARCA3), MCM9, MSH6, POLD3, POLK, RAD51, RAD52, RAD54L, RBI, RECQL, REV3L, RIF1, RNF8, SETD1A, SHPRH, SMARCAL1, TDRD3, TOPBP1, TP53BP1, WRNIP1, XRCC2, WRN, BRCA1, ZRANB3, CDC6, CDT1, POLH, POLI, FANCD2, INO80, FANCB, ASH2L, FAM35A, XRCC3, BRIP1, and RNF168.

The invention discloses a chromosome aneuploid analysis method and application, and the method comprises the following steps: calculating the fetal DNA concentration in a to-be-detected sample and the window depth of the to-be-detected sample in a set window by adopting the sequencing data of the to-be-detected sample and the comparison result of the to-be-detected sample; and calculating the average value of the relative depths of all the samples in the selected reference set in the set window as a correction baseline, correcting the window depth of the to-be-detected sample by adopting the correction baseline, calculating the Z value of the to-be-detected sample according to the corrected window depth, and judging whether the aneuploid abnormality occurs in the fetal chromosome of the to-be-detected sample according to the Z value. According to the method, the to-be-detected sample is corrected by calculating the correction baseline by selecting the reference set, so that the chromosome aneuploid abnormality of the to-be-detected sample can be more stably and accurately detected under the condition that no sample in the same batch is taken as a reference, and the batch fluctuation of detection is reduced.

Aspects herein relate, at least in part, to determining a treatment plan for a cancer patient based on a measured aneuploidy score from cancer cells from the patient.

Inventors determined that recombinant glioblastoma cell lines overexpressing αS- SETMAR (a stable form of S-SETMAR) exhibited a prolonged cell cycle from 27 to 37 hours that leads to a reduction in cell proliferation. The over-expression of αS-SETMAR revealed an unexpected role for this protein as it increased DNA quantity linked to chromosomal chaos, both in terms of chromosomes number (aneuploidy) and organization (chromoanagenesis). Finally, they have noted that αS-SETMAR over-expression makes cells more sensitive to stringent conditions for their survival, such as those used during chemotherapy or radiotherapy treatments. These data allow them to conclude that αS-SETMAR reduces cell proliferation, sensitizes cells to chromosomal chaos and irradiation-induced apoptosis, opening up the possibility of using αS-SETMAR as a therapeutic or prognosis protein. The present invention relates to a method for sensitizing glioblastoma cells to a classical treatment comprising a step of administrating an agonist of αS-SETMAR in a subject in need thereof.