29 results about "Sequence variation" patented technology

The invention discloses a DNA sequence reconstruction method and system based on multi-scale attention and contrast learning, and relates to the technical field of DNA storage data reconstruction. Comprising the following steps: collecting a plurality of DNA sequence copies, screening out abnormal length sequences, and constructing a standardized clustering data set; performing one-hot coding and filling processing on the DNA sequence; extracting context dependent features and cross-sequence variation features; an Inter-Sequence multi-head attention mechanism is constructed to calculate the similarity between the sequences, and a weighted sequence tensor is generated; a global dependency relationship in the sequence is extracted through an Intra-Sequence multi-head attention mechanism; local offset features caused by insertion and deletion errors are extracted through a multi-size convolutional network; inputting a double-layer long-short-term memory network for sequence-level modeling, and outputting base reconstruction probability distribution; and constructing positive and negative sample pairs, calculating comparison loss, combining cross entropy loss to form a joint loss function, and outputting a high-precision DNA sequence reconstruction result. The method has high accuracy and robustness under the conditions of complex noise and multiple types of errors.

The invention relates to a full-length sequence amplification primer, an amplification method and a three-generation sequencing method of an HLA-I antigen gene, and belongs to the field of gene detection. The HLA-I antigen gene is subjected to PCR (Polymerase Chain Reaction) amplification by using 8 pairs of characteristic amplification primers. And each gene can be subjected to high-yield specific amplification on a full-length sequence containing complete intron and exon regions only through one round of amplification and enrichment, and 7.8 Kb long-fragment genes can be captured once at most. The experimental deviation caused by simultaneous amplification of a single gene by using a plurality of pairs of segmented primers and the indirect error caused by gene splicing are effectively avoided. The method comprises the following steps: carrying out quality inspection and purification on amplicon PCR (Polymerase Chain Reaction) products, mixing samples, constructing an HLA-I type antigen gene library, carrying out accurate and complete sequencing on the full-length sequence of the HLA-I type antigen gene by adopting a three-generation PacBio Sequel II platform, and ensuring that the Hifi reads base accuracy can reach 99% or above. The reading of HLA-I type antigen gene full-length sequence variation information and the haplotype analysis at a high resolution level can be realized.

A method of enhancing grain yield of a Gramineae plant is provided. The method comprises:(a) crossing a recipient plant with a donor plant comprising a sequence variation in a TPR allele, said sequence variation imparting enhanced grain yield; and(b) selecting a progeny plant of said crossing comprising said sequence variation by identifying said variation, said progeny plant being characterized by an improved grain yield relative to said recipient plant. Also provided are plants and processed products resultant of the method.

The present invention pertains to a method for determining DNA sequence variation in a fetus from samples of the fetus and parents using a Bayesian framework. The method comprising the following steps: receiving the samples comprise genomic sequence data covering one or more genomic regions of interest in relation to the fetus and the parents; processing the received samples at least in part based on a reference genome; computing a probability of fetal genotypes based on the samples using the Bayesian framework, where the Bayesian framework computes a posterior probability of whether a DNA sequence variant is present in the samples based on a prior probability and a likelihood function; and determining, based on the posterior probability of fetal genotypes, whether the DNA sequence variant is present in the fetus.

The present invention provides a method for detecting single-cell gene sequence variation in rice and its application, which belongs to the field of agricultural technology. The method of the present invention mainly includes three aspects: sampling, sequencing and bioinformatics analysis, wherein the sampling is to obtain a single rice microspore sex cell. The present invention successfully isolates a single rice microspore sex cell, and improves the defects of the existing rice single-cell variation detection technology process, such as weak integrity and detection consistency that need to be improved. In addition, the authenticity of the mutation site is identified and confirmed by heavy ion mutagenesis technology. The method of the present invention broadens the source range of rice single-cell mutagenic materials, and provides new ideas and methods for creating more diverse breeding materials and conducting more efficient mutagenic breeding. At the same time, microspore sex cells serve as male gametes, and the mutations carried in the genome can be passed into the offspring through hybridization, which can realize the inheritance and fixation of mutations, and also provide a way to quickly utilize excellent mutant genes.

The invention provides methods for identifying rare variants near a structural variation in a genetic sequence, for example, in a nucleic acid sample taken from a subject. The invention additionally includes methods for aligning reads (e.g., nucleic acid reads) to a reference sequence construct accounting for the structural variation, methods for building a reference sequence construct accounting for the structural variation or the structural variation and the rare variant, and systems that use the alignment methods to identify rare variants. The method is scalable, and can be used to align millions of reads to a construct thousands of bases long, or longer.

The invention discloses a hybrid production flexible assembly job shop scheduling method considering multi-assembly sequence change and transportation tasks based on a Q-Learning model algorithm. The method comprises the following steps: S1, establishing a scheduling model taking total production completion time, total inventory time and total manpower cost as optimization targets; s2, providing a Q-Learning memetic algorithm to solve the scheduling model, designing a five-layer segmented mixed chromosome coding structure and a two-subgeneration chromosome updating method, and introducing a variable neighborhood search strategy and an elite retention strategy; s3, adaptively adjusting the cross range of the chromosomes through Q-Learning to improve the algorithm efficiency; and S4, through comparison with other three algorithms, validity and robustness of the proposed algorithm are verified. Based on the scheduling method provided by the invention, the processing and assembling sequences of product parts can be optimized simultaneously in the scheduling process of multi-product mixed production and consideration of transportation tasks, and meanwhile, machines, workers and AGV resources are reasonably allocated, so that the production cycle of products is effectively shortened.

A method for sequence variant detection using deep learning is disclosed. This disclosure provides methods, systems, and computer program products for accurately and effectively detecting variants in biopolymer sequencing data, particularly suboptimal sequencing data, using embeddings of candidate variant information and deep learning models.

Methods and systems are provided for validating variant calls. Sequencing data is received for a sample read along the genomic sequence of interest. An indication is received of a potential variant call at a designated position within the sequence of nucleotides along the genomic sequence of interest. The methods and systems obtain baseline variant frequencies at the designated position within one or more baseline genomic sequences, determine a sample variant frequency at the designated position for the genomic sequence of interest, analyze the baseline and sample variant frequencies at the designated position to obtain a quality score, and validate the potential variant call for the genomic sequence of interest based on the quality score.

The present disclosure relates to methods and compositions for the approximately simultaneous amplification of RNA / cDNA and genomic DNA. The present disclosure further provides methods of producing an RNA library for transcriptome analysis and a DNA library for DNA sequence variation analysis. The present disclosure further provides methods of identifying a DNA sequence variation or a transcriptome variation in a sample. Aspects of the present disclosure further relate to a DNA library or RNA library produced by the methods of the present disclosure.

The invention discloses a CAPS molecular marker developed based on a ZmMYB24 gene and related to salt resistance and low temperature resistance of corn and application of the CAPS molecular marker. Sequence variation of a ZmMYBR24 gene coding region induced and expressed by salt stress and low-temperature stress in different corn homozygous inbred lines is analyzed, correlation analysis is carried out on salt tolerance and low-temperature resistance of the corn homozygous inbred lines, correlation sites are mined, and then the CAPS molecular marker related to salt tolerance and low-temperature resistance of corn is developed and named as CAPs814. The molecular marker CAPs814 is used for marker-assisted selection, the average detection efficiency in identification of maize inbred lines with medium salt resistance and medium low temperature resistance or above is 80.56% and 86.11% respectively, and the molecular marker CAPs814 provides a new technical means for screening maize materials with medium salt resistance and low temperature resistance.

The invention relates to the technical field of biological information, and discloses a virus host prediction model and a training method and device.The virus host prediction model comprises a basic model and a classification model, and the basic model comprises an autoregression pre-training model and a low-rank adaptation unit inserted into the autoregression pre-training model; on the basis of the human genome sequence, the sequence characteristic relation of the genome is learned in an autoregression mode, and the sequence characteristic relation is represented as the general representation of the gene sequence; furthermore, a low-rank adaptation unit is added when transfer learning is carried out on the autoregression pre-training model, and the low-rank adaptation unit continuously learns subtle features which are difficult to perceive in a virus sequence by utilizing a causal relationship before and after a gene sequence, so that the sensitivity and the adaptability to virus sequence variation are improved. The virus host prediction model has good generalization ability after being fully trained, and can perform effective potential host prediction on unknown or new virus sequences.

The invention relates to the field of biological medicine, and discloses an integrated genome analysis method based on low-depth sequencing, and the method comprises the following steps: obtaining whole genome low-depth sequencing data; after quality control and comparison, SNV, Indel and CNV are calculated; performing multi-dimensional function annotation by combining genome position, coding influence, splicing disturbance, conservative property, regulatory element and three-dimensional chromatin interaction; database information such as ClinVar and HGMD is integrated, and according to a phenotype-driven rule engine, a clinical interpretable report is generated according to the ACMG / AMP standard. According to the method, a complete analysis chain covering sequence variation detection, multi-dimensional function annotation, three-dimensional genome association, public database integration and phenotype driven interpretation is constructed, so that the fundamental defect that only an original variation list is output and a clinical action basis cannot be provided in traditional low-depth sequencing is overcome.

Provided herein is method for, among other things, estimating the number of sequence variations in a sample of DNA. In some embodiments, the method can be used to estimate the mutational load of a sample. In some embodiments, the method makes use of a set of primers that have 3′ ends that specifically hybridizes to a sequence that is repeated multiple times in the genome. Thermocycling a reaction mix containing the primers may produce a reaction product comprising at least 50 amplicons having a total length of at least 100 kb. This product can be sequenced to provide an estimate of the number of sequence variations in the sample, and thus the mutational load of the sample.

The present disclosure relates to methods and compositions for producing a DNA sequencing library for one or more DNA sequences of interest using a k-mer analysis strategy. The present disclosure further provides methods of producing a DNA library for analysis of one or more DNA sequences of interest and methods of identifying a DNA sequence variation or a modification in a DNA sequence of interest. Aspects of the present disclosure further relate to a DNA library produced by the methods of the present disclosure.

The invention provides novel methods for evaluating levels of microsatellite instability in a sample and evaluating the biological significance of sequence variations identified in a sample during sequencing. The invention further relates to the use of novel microsatellite instability markers for evaluating levels of microsatellite instability in a sample and evaluating the biological significance of sequence variations identified in a sample during sequencing. Corresponding kits are also provided.

In some aspects, the present disclosure provides methods for identifying sequence variants in a nucleic acid sample. In some embodiments, a method comprises identifying sequence differences between sequencing reads and a reference sequence, and calling a sequence difference that occurs in at least two different circular polynucleotides, such as two circular polynucleotides having different junctions, as the sequence variant. In some aspects, the present disclosure provides compositions and systems useful in the described methods.

Disclosed are methods for detecting a single nucleotide variant in a tissue sample. The methods comprising; a) obtaining or having obtained the tissue sample, wherein the tissue sample comprises DNA, non-RNA molecules, and RNA, wherein the RNA comprises a single nucleotide variant; b) permeabilizing the tissue sample; c) substantially degrading the DNA in the tissue sample; and d) introducing to the tissue sample a primer or a probe specific to the single nucleotide variant, wherein the primer or probe binds to the single nucleotide variant; and e) detecting the primer or probe bound to the single nucleotide variant, thereby detecting the single nucleotide variant in the tissue sample.

The invention belongs to the technical field of molecular biology, and particularly relates to a transcriptional activation domain AD, an artificial transcription factor and application thereof. The invention provides a transcriptional activation domain AD. A skeleton sequence of the transcriptional activation domain AD comprises: (1) at least one core sequence 1-5 as shown in SEQ ID NO.11-15; and (2) a variation sequence of at least one of the core sequences 1-5, wherein the variation sequence and at least one of the core sequences 1-5 have at least 98% sequence consistency. The transcriptional activation domain AD provided by the invention can be subjected to fusion expression with original transcription factors of an organism, activates expression of biosynthesis related genes of anthocyanin and glycoside derivatives of the anthocyanin, has stronger transcriptional activation capability compared with original protein, and promotes accumulation of the anthocyanin and the glycoside derivatives of the anthocyanin of plants.

The invention provides a gRNA sequence integrity and accuracy detection method, a template adapter and a kit, a specific adapter sequence is connected to the 3'terminal of a to-be-detected gRNA sequence, and magnetic bead purification is carried out to obtain a gRNA adapter connection product; carrying out reverse transcription on the gRNA adapter connection product, and adding a template conversion adapter to obtain cDNA (complementary deoxyribonucleic acid); carrying out PCR (Polymerase Chain Reaction) amplification and purification on the cDNA by using the primer to obtain a sequencing library; performing high-throughput sequencing on the sequencing library; and performing signal analysis on the sequencing result to determine the integrity and accuracy of the gRNA sequence. According to the high-sensitivity detection method based on high-throughput sequencing, single-base-resolution full-length sequence analysis can be carried out on gRNA, base variation and sequence integrity can be accurately recognized, clinical risks caused by gRNA sequence variation and low purity can be avoided from the source, and the sensitivity of gRNA detection is improved. And key data support can be provided for effectiveness and safety of gene editing drugs.

The application discloses a method for preparing grape DNA identification codes by DNA sequence variation and application thereof; the application utilizes multiple pairs of SSR primers to perform PCR amplification on grape germplasm resource genomic DNA, clear and polymorphic SSR fingerprint bands are obtained through gel electrophoresis, and information on the presence or absence of bands of different lengths in the amplification products is converted into 0 / 1 binary data. On the basis of gradually screening and combining multiple pairs of SSR primers to realize complete differentiation of varieties, the multiple-bit binary data is converted into a decimal number in a radix conversion mode, and finally, a unique DNA identification code of each sample is generated through a specific conversion method; a high-efficiency technology for genotype identification by using plant DNA sequence variation is formed, the germplasm resource identification capability is significantly improved, and the technology is suitable for scenes such as plant genetic diversity analysis, germplasm authenticity and purity identification, variety specificity identification and the like.

The present invention relates to a vaccine composition for preventing influenza virus infection, having enhanced neutralizing activity. A variant protein or fragment thereof according to the present invention has a stable pre-fusion structure, thereby enabling rapid preparation for influenza viruses with sequence variations that are difficult to predict each year. In addition, the variant protein or fragment thereof according to the present invention exhibits high neutralizing activity, thereby serving as an effective vaccine with superior protective ability against influenza virus. In particular, sequence optimization enables the efficient production of structurally stable proteins with high expression levels, while reducing production costs.

The invention establishes a method for dynamically setting a short sequence variation blank limit, and strictly utilizes the information of a blank sample to specifically and dynamically define the variation LoB for the variation depth to be measured. According to the method, LoBs of all SNVs and indel in the ROI of the detected sample can be defined, and the accuracy of variation detection is improved.

Variation in a single nucleotide of a target or template nucleic acid may be significant in many ways. For infectious disease, many drug resistance mutations are known and a simple means to confine their absence would more quickly match a patient with an infection with the most effective treatment. This disclosure provides for a simple, low resource strategy allowing the detection of single nucleotide variation using only low-cost diagnostic methods already available in many locations. A key to this approach is the use of left-handed DNA (L-DNA) as a comparator molecule for D-DNA targets. L-DNA provides numerous additional advantages such as low cost and stability.

Sequence variants and copy number variations in the EGFR, KRAS and MET genes are biomarkers for resistance to anti-EGFR therapies for cancer. This disclosure provides methods of detecting these biomarkers and using them in the diagnosis and treatment of cancer.

The invention relates to a three-generation library building and sequencing method for a full-length sequence of an HLA (Human Leukocyte Antigen)-III antigen gene, and belongs to the field of gene detection. According to the invention, PCR amplification is carried out on HLA-III type antigen genes by using five pairs of characteristic amplification primers. And each gene can be subjected to high-yield specific amplification on a full-length sequence containing complete intron and exon regions only through one round of amplification and enrichment, and 14Kb long-fragment genes can be captured once at most. The experimental deviation caused by simultaneous amplification of a single gene by using a plurality of pairs of segmented primers and the indirect error caused by gene splicing are effectively avoided. The HLA-III type antigen gene library is constructed by carrying out quality inspection and purification on amplicon PCR products and then carrying out sample mixing, the full-length sequence of the HLA-III type antigen gene is accurately and completely sequenced by adopting a three-generation PacBio Sequel II platform, and the Hifi reads base accuracy rate can reach 99% or above. The reading of HLA-III type antigen gene full-length sequence variation information and the haplotype analysis at a high resolution level can be realized.

The invention relates to a full-length sequence amplification primer, an amplification method and a three-generation sequencing method of an HLA-II antigen gene, and belongs to the field of gene detection. According to the invention, PCR amplification is carried out on HLA-II type antigen genes by using 10 pairs of characteristic amplification primers. Each gene can be subjected to high-yield specific amplification on a full-length sequence containing complete intron and exon regions only through one round of amplification and enrichment, and 17Kb long-fragment genes can be captured once at most. The experimental deviation caused by simultaneous amplification of a single gene by using a plurality of pairs of segmented primers and the indirect error caused by gene splicing are effectively avoided. The method comprises the following steps: carrying out quality inspection and purification on amplicon PCR (Polymerase Chain Reaction) products, carrying out sample mixing, constructing an HLA-II antigen gene library, carrying out accurate and complete sequencing on the HLA-II antigen gene full-length sequence by adopting a three-generation PacBio Sequel II platform, and ensuring that the Hifi reads base accuracy can reach 99% or above. The reading of HLA-II type antigen gene full-length sequence variation information and the haplotype analysis at a high resolution level can be realized.

The present invention relates to the medical field of single-gene disorders caused by functional loss or gain of an allele. The innovative approach developed being based on editing the human genome at the level of the Kozak sequence by means of CRISPR-Cas programmable nucleases. Particularly, the present invention relates to variant Kozak sequences and related in vitro or in vivo methods for obtaining such variant Kozak sequences for therapeutic applications in the treatment of single-gene diseases caused by monoallelic losses or gains. These in vitro and in vivo methods include CRISPR-Cas homology-directed repair, CRISPR-Cas prime editing, CRISPR-Cas base editing or genome editing with other programmable RNA-guided nucleases, and the introduction of specific nucleotide conversions in the Kozak sequence of genes causative of diseases. These nucleotide conversions enhance or inhibit the translation of the mRNA produced by the gene, compensating for the functional loss or gain of one allele in the diseases.