354 results about "Variome" patented technology

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

The invention discloses a protein optimization design and screening method and device based on an artificial intelligence algorithm, and the method takes fungal luciferase as an example, and integrates multi-dimensional bioinformatics analysis and deep learning technology to realize efficient protein engineering transformation and optimization. The method comprises the following steps: firstly, identifying a binding domain of luciferase and fluorescein by utilizing an AI-driven molecular docking simulation method, and determining a key conservative site by combining literature, evolutionary analysis and structural prediction; then, generating a protein functional domain skeleton under the constraint of a fixed site by adopting a diffusion model, and performing protein sequence prediction by utilizing a graph neural network model; and finally, scoring and screening the generated sequences to obtain high-stability candidate variants. According to the method, a conservative site dynamic fusion strategy is innovatively constructed, a fixed region is optimized through logic of structure prediction, evolution site intersection priority and literature site union set expansion, the diversity and adaptability of a protein design sequence are met, and the efficiency bottleneck of a traditional scheme is broken through.

A system and method for processing genomic data using dynamic latent manifolds that transforms multi-modal genomic datasets into geometric representations within a curved manifold space. The system receives genomic datasets including DNA sequences, genetic variants, and expression data, then extracts biological features and assesses importance using trained neural networks. Manifold curvature values are computed based on biological significance, and genomic data is embedded as geometric structures where semantic relationships are represented through distance and curvature properties. The system generates compression pressure fields that influence processing decisions and computes optimal geodesic paths through the manifold to minimize cognitive action functionals. Adaptive compression rates are determined for different genomic regions based on geometric properties and biological importance. The manifold structure evolves through use, strengthening frequently accessed pathways while applying thermodynamic decay to unused concepts. The system supports hierarchical organization across biological scales, reversible navigation, and federated learning capabilities that enable privacy-preserving collaboration.

Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids or the modification of nucleic acids or proteins, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of nucleic acid programmable DNA binding proteins e.g., GeoCas9 or variants thereof, and effector domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing or protein modification are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a GeoCas9 and effector domains, are provided.

Among other things, the present disclosure pertains to methods and compositions related to phasing of allelic variants of genetic loci. Phasing of allelic variants of genetic loci on an individual patient's chromosomes is highly valuable for many purposes, including patient stratification for allele-specific therapeutics.

There is provided a fluorinase variant thereof having at least 70% sequence identity to a sequence MSDLGX6TDDSVAQCKGLMLSICPX24VX26IX28DX30CHX33MTPX37DVVEGARYIVDLPR X52FPEGTVFATTTYPATGTX70X71RSVAX76RX78KX80AALGGARGQX90AGSGX95GX97E RAEGX103YIYIAPNNGLLTX116VIEEHGYX124EAYEVSX131TX133VIPX137X138PEPTFYSR EMVAIPSAHLAAGFPLX163X164VGRX168LX170DX172EIVRFEX179X180KX182X183X184VX186G X188X189LX191GX193X194X195X196X197DHPFGNX204WTNX208HRTDLEKAGIX219YX221TX223X 224KX226VX228DGVLX233FX235LPLX239PTFADAX246X247X248GX250PVX253YX255NSRGYLX2 62X263ARNAAX269LAYPYNLX277AGX280SVX283VTX286A (SEQ ID NO: 1), wherein X is a natural amino acid, and wherein the variant comprises one or more mutations at a site selected from the group consisting of an ion-egress site, a S-Adenosyl-L-Methionine (SAM) binding site, an ion-binding site (IBS), and a conserved site. Also disclosed are polynucleotides encoding the variants, vectors comprising the polynucleotides encoding the variants, and host cells comprising the vectors thereof. Also disclosed are Methods for producing the variants, methods of catalyzing the fluorination of a compound, uses of the fluorinase variants, and methods of treatment using the fluorinase variants thereof.

The present disclosure relates in some aspects to methods for analyzing target nucleic acids and their spatial locations in a biological sample. In some aspects, the presence / absence, amount, and / or identity of variant sequences (e.g., single nucleotide variations such as SNPs or point mutations) in a plurality of target nucleic acids in a cell or tissue sample are analyzed in situ in the sample. Also provided are compositions and kits for use in accordance with the methods.

Strategies, systems, methods, reagents, and kits for phage-assisted continuous evolution are provided herein. These include strategies, systems, methods, reagents, and kits allowing for stringency modulation to evolve weakly active or inactive biomolecule variants, negative selection of undesired properties, and / or positive selection of desired properties.

Processes that determine transcriptional regulation from genetic sequence data are described. Generally, computational models are trained to predict transcriptional regulatory effects, which can be used in several downstream applications. Various methods further develop research tools, develop and perform diagnostics, and treat individuals based on identified variants.

A method for performing local alignment based on a query sequence of DNA and a reference sequence of DNA includes: obtaining a bit matrix H; determining at least one diagonal based on the bit matrix H; for each of the at least one diagonal, calculating an initial score for the diagonal, determining at least one trace region, determining a sub-alignment for each of the at least one trace region, consolidating the diagonal and the sub-alignment respectively of the at least one trace region to obtain an alignment, and obtaining an alignment score based on the initial score and the partial score respectively of the sub-alignment respectively of the at least one trace region; and among each of the at least one alignment thus determined respectively for each of the at least one diagonal, reserving one of the at least one alignment that has the highest alignment score therefrom.

We introduce a variant classifier that uses trained deep neural networks to predict whether a given variant is somatic or germline. Our model has two deep neural networks: a convolutional neural network (CNN) and a fully-connected neural network (FCNN), and two inputs: a DNA sequence with a variant and a set of metadata features correlated with the variant. The metadata features represent the variant's mutation characteristics, read mapping statistics, and occurrence frequency. The CNN processes the DNA sequence and produces an intermediate convolved feature. A feature sequence is derived by concatenating the metadata features with the intermediate convolved feature. The FCNN processes the feature sequence and produces probabilities for the variant being somatic, germline, or noise. A transfer learning strategy is used to train the model on two mutation datasets. Results establish advantages and superiority of our model over traditional classifiers.

The invention provides a genome editor enDelIscB and a genome editor enDelIscB-T5E based on an IscB system, and further provides a base editor ICBE and a base editor IABE based on the enDelIscBD60A. According to the invention, a genome editor and a base editor which are more compact in size and higher in cleavage activity and insertion / deletion efficiency are realized by optimizing a single mutation site of the activity of a DelIscB protein cleavage plasmid, an optimized variant of the DelIscB protein and an optimized sgRNA variant of the DelIscB. According to the present invention, it is verified that the albinism model is efficiently constructed by using the enDelIscB editor and the enDelIscB-T5E editor through micro-injection of the mouse embryo, such that the enDelIscB editor and the enDelIscB-T5E editor have great potential in the field of genome editing.

The present disclosure relates in some aspects to methods for analyzing target nucleic acids and their spatial locations in a biological sample. In some aspects, the presence / absence, amount, and / or identity of variant sequences (e.g., single nucleotide variations such as SNPs or point mutations) in a plurality of target nucleic acids in a cell or tissue sample are analyzed in situ in the sample or using a spatial array. Also provided are oligonucleotides, sets of oligonucleotides, compositions, and kits for use in accordance with the methods.

Methods for detection and classification of reversion mutations are described. The methods may comprise, for example, receiving sequence data for nucleic acid sequences that reside within one or more gene loci within a subgenomic interval in a sample from a subject; identifying a gene locus of the one or more gene loci for which the gene locus comprises two or more variant sequences; categorizing the two or more variant sequences in the gene locus according to a structural feature or functional effect; comparing the structural features or functional effects of the two or more categorized variant sequences in the gene locus; and classifying the two or more categorized variant sequences in the gene locus based on the comparison, where the classification indicates whether the two or more categorized variant sequences comprise a reversion mutation.

The invention provides a vaccine target screening system based on calculation model simulation. The vaccine target screening system comprises a multi-source heterogeneous database, wherein the multi-source heterogeneous database integrates and standardizes pathogenic genes, protein structures, literatures and experimental data; the feature calculation module calls a calculation biological model to carry out structural analysis, immunogenicity simulation and stability prediction; the intelligent screening and sorting module applies a multi-objective optimization algorithm to perform parallel evaluation and outputs optimal target spots; a structure iteration optimizer automatically iteratively corrects the optimized target spots to generate a high-potential variant library; and the process suitability simulation module couples the variants with the preparation formula and the process parameters to simulate production storage behaviors and feeds back an optimization target. According to the invention, efficient screening and optimization of vaccine targets can be realized, the accuracy and efficiency of target screening are improved, the research and development cost is reduced, and the research and development process of vaccines is accelerated.

The present disclosure provides compositions and methods for prime editing with improved editing efficiency and / or reduced indel formation by inhibiting the DNA mismatch repair path way while conducting prime editing of a target site. Accordingly, the present disclosure provides a method for editing a nucleic acid molecule by prime editing that involves contacting a nucleic acid molecule with a prime editor, a pegRNA, and an inhibitor of the DNA mismatch repair pathway, thereby installing one or more modifications to the nucleic acid molecule at a target site with increased editing efficiency and / or lower indel formation. The present disclosure further provides polynucleotides for editing a DNA target site by prime editing comprising a nucleic acid sequence encoding a napDNAbp, a polymerase, and an inhibitor of the DNA mismatch repair pathway, wherein the napDNAbp and polymerase is capable in the presence of a pegRNA of installing one or more modifications in the DNA target site with increased editing efficiency and / or lower indel formation. The disclosure further provides, vectors, cells, and kits comprising the compositions and polynucleotides of the disclosure. The present disclosure also provides compositions and methods for prime editing with improved editing efficiency and / or reduced indel formation with modified prime editor fusion proteins. The disclosure further provides, vectors, cells, and kits comprising the compositions and polynucleotides of the disclosure.

To improve allele discrimination, the inventors adapted the system combining Cas13a detection sensitivity with allele-specific PCR amplification to propose CASPER (Cas13a Allele-Specific PCR Enzyme Recognition) as a new versatile, easy-to-implement, and highly sensitive method to detect low-frequency of sequence variant. CASPER enabled specific and sensitive detection of KRASG12D with low DNA input such as DNA extracted from patient's pancreatic ultrasound-guided fine-needle aspiration fluids. CASPER is easy to implement and a versatile reliable method virtually adaptable to any point mutation.

The technology disclosed relates to detecting gene conservation and expression preservation. In particular, the technology disclosed relates to detecting gene conservation and epigenetic signals for a reference genetic sequence in comparison to a variant of the reference genetic sequence at base resolution through the generation of a plurality of alternative representations of the sequence in chromatin form which may represent evolutionary conservation, transcription initiation, or epigenetic signals, mapping the plurality of alternative chromatin sequences to a gene expression alterability classifier to generate a gene expression class prediction for the variant, and mapping the alternative chromatin sequence to a pathogenicity predictor to detect pathogenicity of variants.

Provided herein are methods for determining allele-specific telomere length (ATL) and telomere variant repeat (TVR) sequences from long read sequencing data. In some embodiments, the methods include clustering telomere reads together into individual alleles using their adjacent TVR regions from which allele-specific TL can then be determined.

Streptococcus pyogenes Cas9 (SpCas9) variants with relaxed PAM requirements capable of high-resolution editing for various applications, and methods of use thereof.

Methods for detecting a tumor using a sample in which tumor DNA fragments are present only in a very low concentration, beyond the statistical limit of detection, where methods include: obtaining sequence data for tumor nucleic acid from a tumor from a subject and analyzing the sequence data to identify a plurality of tumor-specific variants that are in the tumor nucleic acid and that are not in non-tumor nucleic acid of the subject; selecting a marker variant that appears duplicated in tumor nucleic acid (compared to non-tumor nucleic acid) a greater number of times than other ones of the tumor variants; performing an assay to detect the marker variant in a sample from the subject; and reporting the presence of the tumor in the subject when the assay is positive for the marker variant in the sample.

The invention discloses a double-CRISPR (clustered regularly interspaced short palindromic repeats) coupled isothermal amplification efficient detection technology, and a double-CRISPR coupled isothermal amplification reagent provided by the invention comprises a pair of efficient Cas12a variant-guide RNA (Ribonucleic Acid) complexes, an isothermal amplification system, bovine serum albumin, a fluorescence resonance energy transfer single-stranded DNA (Deoxyribose Nucleic Acid) probe, a reaction buffer solution and target nucleic acid to be detected, the double CRISPR coupling isothermal amplification detection technology disclosed by the invention has the remarkable advantages of high reaction speed, high signal-to-noise ratio, high sensitivity and strong specificity, can efficiently detect low-copy or low-quality target nucleic acid, and can be combined with a 3D printing chip to realize reagent freeze-drying and simultaneous detection of multiple types of target nucleic acid; the method shows a great application prospect, and particularly has a great potential in detection of bacteria deployed on site.

An Interferon Gamma Inducible Protein 16 (IFI16) mutant gene and its use as a marker for predicting, diagnosing, or prognosticating risk or severity of chronic liver disease is described. As a result of performing genomic analysis on NAFLD and NASH patient groups, it was confirmed that the frequency of IFI16 single-nucleotide variants (SNVs) including rs2276404, rs73021847, rs7532207, and rs6940 was increased, and the expression of the IFI16 mutant gene was increased depending on the disease stage of liver disease. The IFI16 SNV was highly expressed in infiltrating macrophages, playing a role in macrophage-induced inflammatory processes, and the IFI16 variant bound more strongly to dsDNA than wild-type IFI16, exacerbating the impaired mitochondrial DNA-sensing response signaling of the IFI16-PYCARD-CASP1 pathway. Thus, the IFI16 mutant gene may be used for predicting, diagnosing, or prognosticating risk or severity of chronic liver disease.

The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

The disclosure relates to novel plants, plant parts, and nucleotide sequences in soybean plants comprising a mutated JAG1 gene, along with methods of using and making the same. Wherein the mutated JAG1 gene comprises a null mutation in the JAG1 gene encoding the polypeptide of SEQ ID NO: 10 or an allelic variant thereof and wherein the soybean plant cell lacks a loss-of-function mutation in the soybean JAG2 gene.

Described herein are variants of alpha-hemolysin having at least one mutation, such as a mutation to a positive charge. In certain examples, the mutation is selected from V149K, E287R, H35G, T109K, P151K, K147N, E111N, M113A, or combinations thereof in the mature, wild-type alpha-hemolysin amino acid sequence. The α-hemolysin variants may also include a substitution at H144A and / or a series of glycine residues spanning residues 127 to 131 of the mature, wild-type alpha hemolysin. Also provided are nanopore assemblies including the alpha-hemolysin variants, the assembly having a decreased time-to-thread. The decreased time-to-thread, for example, increases DNA sequencing efficiency and accuracy.

The present application is directed to a method for identifying at least one candidate (Loc), namely a gene location and / or a sequence variant, indicative for at least one selected (phenotypic) trait of an organism, in particular of a plant, comprising the steps of:a. receiving a plurality of candidate lists (Can1, Can2, Can3) of candidates (Loc), the candidate lists being ordered;b. receiving a reference set (RefDB) with gene locations and / or sequence variants;c. matching at least a subset of candidates (Loc) from the candidate lists (Can1, Can2, Can3) with the reference list (RefDB) to determine an evaluation value (EV) for at least the subset;d. assigning each evaluation value (EV) to the respective candidate (Loc) in the respective candidate lists (Can1, Can2, Can3);e. calculating for each candidate list a performance value based on the evaluation value (EV), in particular by using the evaluation values (EV);f. selecting at least one candidate (Loc) as (preferred) candidate (Loc) from one of the candidate lists (Can1, Can2, Can3) using the performance values.

Described herein are methods of generating a coupled sequencing read pair for a polynucleotide, and methods of analyzing the coupled sequencing read pair. The coupled sequencing read pair can be analyzed to detect polynucleotide variants, including at loci that are not directly sequenced within the coupled sequencing read pair. Other analytical methods can include using coupled sequencing read pairs to construct or validate a consensus sequence. The coupled sequencing read pair may be generated for a polynucleotide by generating sequencing data for a first region by extending a primer using labeled nucleotides; further extending the primer through a second region using nucleotides provided in a second region flow order, wherein primer extension through the second region is faster than primer extension through the first region; and generating sequencing data associated with a sequence of a third region of the polynucleotide by further extending the primer using labeled nucleotides.

A genetic prime editing screening platform to identify functional variants related to human health and disease, is configured substantially to annotate genome with nucleotide resolution with actionable disease prediction and treatment for personalized medicine.

The technology disclosed relates to reliably identifying variants that cause extreme levels of gene expression. Extreme levels of gene expression include under expression and over expression. Then, these variants are used to train artificial intelligence based models for a variety of prediction tasks. One example of the prediction tasks is to produce per-base resolution for chromatin sequences. Another example of the chromatin task is to produce gene expression changes caused by the reliably identified variants.