Abstract: The present invention provides a novel antisense oligonucleotide and a composition for preventing or treating glycogen storage disease type Ia. The present invention provides an antisense oligonucleotide which hybridizes with a pre-mRNA sequence derived from a region including at least one of a base at position 42911000, a base at position 42911004, and a base at position 42911005 in a base sequence of human chromosome 17 of GRCh38/hg38 and has activity to inhibit aberrant splicing of pre-mRNA of c.648G>T variant G6PC.

Abstract: An electrochemical sensor incorporates a ferrocenophane which is a compound with at least one bridging group covalently attached to and connecting the two cyclopentadiene rings associated with the same iron atom. This bridging group maybe tetramethylene. As compared to an equivalent sensor with ferrocene, the tolerance of elevated temperature is improved and so is the working life at ambient temperature.

Abstract: The present invention establishes a molecular therapy for glycogen storage disease type Ia. The present invention provides an oligonucleotide of 15-30 bases comprising a nucleotide sequence complementary to die cDNA of G6PC gene with c.648G>T mutation, wherein the oligonucleotide comprises a sequence complementary to a region comprising any site between the 82nd to the 92nd nucleotide from the 5? end of exon 5 of the G6PC gene with c.648C>T mutation, a pharmacologically acceptable salt or solvate thereof. Also provided is a pharmaceutical drug comprising the oligonucleotide, a pharmacologically acceptable salt or solvate thereof (e.g., therapeutic drug for glycogen storage disease type Ia).

Abstract: Methods for analyzing DNA-containing samples are provided. The methods can comprise isolating a single genomic equivalent of DNA from the DNA-containing sample to provide a single isolated DNA molecule. The single isolated DNA molecule can be subjected to amplification conditions in the presence of one or more sets of unique molecularly tagged primers to provide one or more amplicons. Any spurious allelic sequences generated during the amplification process are tagged with an identical molecular tag. The methods can also include a step of determining the sequence of the one or more amplicons, in which the majority sequence for each code is selected as the sequence of the single original encapsulated target. The DNA-containing sample can be a forensic sample (e.g., mixed contributor sample), a fetal genetic screening sample, or a biological cell.

Abstract: The present invention relates to small interfering RNA (siRNA) molecules against the HTT gene, adeno-associated viral (AAV) vectors encoding siRNA molecules and methods for treating Huntington's Disease (HD) using the siRNA molecules and AAV vectors.

Abstract: Compositions and methods for quantitative detection of target nucleic acids, such as miRNAs are disclosed. The methods are especially advantageous for single-color multiplex detection of two or more targets simultaneously (e.g., in the same reaction). The methods can involve optional reverse transcription followed by amplification performed with universal primers, fluorophore-labeled detection probes, and quencher oligonucleotides for quenching fluorescence of any detection probe not bound to a target molecule. The methods employ differential stability of detection probe-quencher oligonucleotide complexes, and by extension, differential fluorescence at various temperatures to distinguish between different target molecules.

Abstract: In a nanopore sensor, a nanopore disposed in a support structure has a nanopore diameter and nanopore resistance, RPore. A fluidic passage, disposed in fluidic connection between a first fluidic reservoir and the nanopore, has a cross-sectional extent, along at least a portion of the fluidic passage length, that is greater than the diameter of the nanopore and that is less than the fluidic passage length. The fluidic passage has a fluidic passage resistance, RFP, of at least about 10% of the nanopore resistance, RPore, and no more than about 10 times the nanopore resistance, RPore. The nanopore is disposed in fluidic connection between the fluidic passage and a second fluidic reservoir. At least one electrical transduction element is disposed at the fluidic passage and electrically connected to produce an indication of electrical potential local to the fluidic passage.

Abstract: The present disclosure provides methods for selectively tagging 5-methylcytosine in a DNA sample and using this approach for genome-wide profiling of 5-methylcytosine in a low input DNA sample such as circulating cell-free DNA.

Abstract: A method of barcoding is provided. The method comprises performing a ligation assay on target nucleic acid molecules that are in or on cells or cell organelles to produce ligation products and adding cell-origination barcodes onto the ligation products or complements thereof by a split-pool barcoding process.

Abstract: Polynucleotides and vectors can be used for the expression of a transgene in cells, such as liver cells. The expression of the transgene from the polynucleotides and vectors can be useful in gene therapy. Various methods can be used for expressing the transgene from the polynucleotides and vectors in liver cells.

Abstract: A method for adding cell origination barcodes onto beads is provided. The method comprises: splitting a pool of beads into a plurality of reaction volumes, appending pre-made oligonucleotides onto the beads in the reaction volumes, wherein at least some of the reaction volumes each receive an oligonucleotide that contains a sequence that is different from the other oligonucleotides added to the reaction volumes, pooling the beads and repeating the splitting, appending and pooling steps one or more times to produce a pool of beads that comprise the cell origination barcodes. In the one or more repeats the oligonucleotides that are appended are added to previously appended oligonucleotides to form the cell origination barcodes.

Abstract: A data storage medium is disclosed comprising a solid support matrix including an optional stabilising reagent or reagents in a dry form, for use as a support for artificially synthesised oligonucleotide sequences encoded with data. Preferably the matrix is fibrous (for example cellulose, or glass, fibres) formed into a support of sufficient strength to hold the oligonucleotide sequences. The stabilising reagents are preferably a combination of a weak base, and a chelating agent, optionally, uric acid or a urate salt, and optionally an anionic surfactant.

Abstract: Determining relative relationships of people who share a common ancestor within at least a threshold number of generations includes: receiving recombinable deoxyribonucleic acid (DNA) sequence information of a first user and recombinable DNA sequence information of a plurality of users; processing, using one or more computer processors, the recombinable DNA sequence information of the plurality of users in parallel; determining, based at least in part on a result of processing the recombinable DNA information of the plurality of users in parallel, a predicted degree of relationship between the first user and a user among the plurality of users, the predicted degree of relative relationship corresponding to a number of generations within which the first user and the second user share a common ancestor.

Abstract: A kit for split-pool barcoding is provided. The kit comprises: a binding agent that binds to a target molecule that is in or on cells or cell organelles and at least two sets of assayable polymer subunit (APS) oligonucleotides. In the kit each set comprises at least 10 unique APS oligonucleotides, the APS oligonucleotides in a set each comprise a sequence that distinguishes the APS oligonucleotides from one another, and the APS oligonucleotides from different sets are configured to link together in an ordered fashion to form all or part of a cell or organelle origination barcode.

Abstract: A method of barcoding is provided. The method comprises: providing a population of fixed cells or cell organelles in a first reaction volume, hybridizing oligonucleotide probes to target molecules that are in or on the cells or cell organelles in the first reaction volume, splitting the population of cells or cell organelles into a plurality of second reactions volumes, wherein at least some of the second reaction volumes receive a single fixed cell or cell organelle from the population of fixed cells or fixed cell organelles, and adding cell-specific nucleic acid barcodes onto: the oligonucleotide probes, ligation products comprising the oligonucleotide probes, or complements of the oligonucleotide probes or ligation products, in the plurality of second reaction volumes.

Abstract: The present invention relates to nucleic acid regulatory elements that are able to enhance diaphragm-specific expression of genes, in particular expression in diaphragm as such, or in combination with expression in cardiac muscle and/or skeletal muscle, methods employing these regulatory elements and uses of these elements. Expression cassettes and vectors containing these nucleic acid regulatory elements are also disclosed. The present invention is particularly useful for applications using gene therapy, more particularly diaphragm-directed gene therapy, and for vaccination purposes.

Abstract: The present disclosure provides gene expression profiles that are associated with prostate cancer, including certain gene expression profiles that differentiate between subjects of African and Caucasian descent and other gene expression profiles that are common to subjects of both African and Caucasian descent. The gene expression profiles can be measured at the nucleic acid or protein level and used to stratify prostate cancer based on ethnicity. The gene expression profiles can also be used to identify a subject for prostate cancer treatment. Also provided are kits for diagnosing and prognosing prostate cancer and an array comprising probes for detecting the unique gene expression profiles associated with prostate cancer in subjects of African and/or Caucasian descent.

Abstract: Disclosed herein are embodiments of a signaling conjugate, embodiments of a method of using the signaling conjugates, and embodiments of a kit comprising the signaling conjugate. The disclosed signaling conjugate comprises a latent reactive moiety and a chromogenic moiety that may further comprise a linker suitable for coupling the latent reactive moiety to the chromogenic moiety. The signaling conjugate may be used to detect one or more targets in a biological sample and are capable of being covalently deposited directly on or proximally to the target. Particular disclosed embodiments of the method of using the signaling conjugate comprise multiplexing methods.

Abstract: High surface area coatings are applied to solid substrates to increase the surface area available for solid-phase synthesis of polymers. The high surface area coatings use three-dimensional space to provide more area for functional groups to bind polymers than an untreated solid substrate. The polymers may be oligonucleotides, polypeptides, or another type of polymer. The solid substrate is a rigid supportive layer made from a material such as glass, a silicon material, a metal material, and plastic. The coating may be thin films, hydrogels, microparticles. The coating may be made from a metal oxide, a high-? dielectric, a low-? dielectric, an etched metal, a carbon material, or an organic polymer. The functional groups may be hydroxyl groups, amine groups, thiolate groups, alkenes, n-alkenes, alkalines, N-Hydroxysuccinimide (NHS)-activated esters, polyaniline, aminosilane groups, silanized oxides, oligothiophenes, and diazonium compounds.

Abstract: Disclosed herein are devices, systems, and methods for controlling a translocation speed of a molecule through a nanopore. In some embodiments, a speed-control device comprises at least one fluid-retaining surface, a fluid region, a field-responsive fluid coupled to the fluid-retaining surface and situated in the fluid region. In some embodiments, a system comprises the nanopore, the speed-control device, and a field generator for generating a magnetic or electric field across the fluid region. The viscosity of the field-responsive fluid is dependent on a magnitude of the magnetic or electric field across the fluid region and can be controlled by changing a magnitude of the magnetic or electric field across the fluid region.

Abstract: A single dissolving compound forms plural azeotropes, which can be azeotropically vaporized off at various stages of the treatment process, thus maintaining predictable concentrations of the chemicals present. The treatment process can be performed in the absence of formalin or related compounds which can interfere with the preservation of genetic material. A process for preserving a specimen includes using a dissolving compound that can form a plural number of azeotropes, at least one azeotrope being formed between one or more components of the dissolving compound and specimen-supplied water, and at least one azeotrope being formed between different components of the dissolving compound; successively and azeotropically vaporizing off formed azeotropes; and impregnating the specimen with a support medium.

Abstract: A method for compressing molecular tagged sequence data includes: grouping sequence reads associated with a molecular tag sequence to form a family of sequence reads, corresponding vectors of flow space signal measurements and corresponding sequence alignments, calculating an arithmetic mean of the corresponding vectors of flow space signal measurements to form a vector of consensus flow space signal measurements, calculating a standard deviation of the corresponding vectors of flow space signal measurements to form a vector of standard deviations, determining a consensus base sequence based on the vector of consensus flow space signal measurements, determining a consensus sequence alignment and generating a compressed data structure comprising consensus compressed data, the consensus compressed data including for each family, the consensus base sequence, the consensus sequence alignment, the vector of consensus flow space signal measurements, the vector of standard deviations and the number of members.

Abstract: Described herein are methods, compositions and articles of manufacture involving neutral conjugated polymers including methods for synthesis of neutral conjugated water-soluble polymers with linkers along the polymer main chain structure and terminal end capping units. Such polymers may serve in the fabrication of novel optoelectronic devices and in the development of highly efficient biosensors. The invention further relates to the application of these polymers in assay methods.

Abstract: Methods and kits for identification of lung cancer in a subject based on alterations in DNA methylation at selected genomic loci are provided.

Abstract: A disclosed example includes accessing computer-generated impression records, the computer-generated impression records based on network communications received at a server of a database proprietor from client devices, the computer-generated impression records indicative of accesses to media at the client devices; accessing self-reported demographic data and behavioral data from a database of the database proprietor, the self-reported demographic data and the behavioral data corresponding to user accounts registered with the database proprietor and associated with the client devices; comparing the self-reported demographic data with a probability distribution of higher-accuracy demographic data; determining different adjustments for corresponding ones of self-reported demographics of the self-reported demographic data based on the comparison; adjusting the corresponding ones of the self-reported demographics based on corresponding ones of the different adjustments to generate adjusted user demographic data; a

Abstract: Microfluidic methods of altering the spacing of a stream of objects. In an exemplary method, objects of the object stream may be transported in carrier fluid along a microfluidic channel structure having an inflow region, an outflow region, and an expanded region extending from the inflow region to the outflow region. The expanded region may have a greater cross-sectional area for fluid flow than each of the inflow region and the outflow region. Objects of the object stream may be moved from the inflow region to the expanded region such that at least a subset of such objects are moved closer to one another. Objects of the object stream may be passed from the expanded region to the outflow region to increase a distance between such objects.

Abstract: A method of diagnosing severe sepsis prior to definitive clinical diagnosis. A pattern of gene expression that correlates strongly with a future diagnosis of severe sepsis and organ failure was identified in patients who had their blood drawn at first clinical presentation. The methods comprise identifying a pattern of two or more polynucleotides, whereby the altered expression of these polynucleotides correlates with prospective and actual sepsis. Also methods of identifying agents for treating sepsis based on the characteristics of this gene expression pattern are provided.

Abstract: The present invention relates to method for storing and transmitting information by employing a nucleic acid construct. The nucleic acid construct can include a lock region; a translation key region that corresponds to the identity of a key; and a message region including a nucleic sequence that corresponds to an encrypted message.

Abstract: The present disclosure provides methods for detecting a single-stranded target RNA. The present disclosure provides methods of cleaving a precursor C2c2 guide RNA array into two or more C2c2 guide RNAs. The present disclosure provides a kit for detecting a target RNA in a sample.

Abstract: Methods, apparatuses, and systems having an electronic medical records system which intelligently selects medical findings or related information and maps them to associated genes. An electronic medical records system intelligently selects genes and maps them to associated medical findings or other related information.

Abstract: This disclosure relates to compositions and methods for analyzing a tissue section from a biological sample.

Abstract: A method for determining a mutation in genomic DNA is described. The method is characterized in that the mutation analysis is performed with genomic DNA, in which at least a part of the cytosines contained therein has previously been converted into uracil or another base with a base pairing behavior or molecular weight distinguishable from that of cytosine.

Abstract: The present disclosure provides methods for detecting a single-stranded target RNA. The present disclosure provides methods of cleaving a precursor C2c2 guide RNA array into two or more C2c2 guide RNAs. The present disclosure provides a kit for detecting a target RNA in a sample.

Abstract: A magnetic separation filter has an unsupported magnetically soft material layer having a plurality of pores, and, optionally, a passivation layer disposed on the magnetically soft material layer. The magnetic separation filter may be part of a microfluidic device having a lateral flow channel and a vertical flow magnetic separation filter. The magnetic separation device may be used to separate magnetically tagged particles, such as cells.

Abstract: As described below, disclosed herein are methods of analyzing DNA methylation in cell-free DNA (cfDNA) and genomic DNA (gDNA) from sequencing data.

Abstract: Disclosed examples include accessing a search term from a client device; accessing a first identifier, the first identifier corresponding to a first database proprietor, the first identifier to access first user information corresponding to a user of the client device; accessing a second identifier, the second identifier corresponding to a second database proprietor, the second identifier to access second user information corresponding to the user of the client device; providing the search term, the first identifier, and the second identifier in a message; and transmitting the message to a server.

Abstract: Methods, systems, and apparatus, including computer programs encoded on computer storage media, for using machine learning models for plant biotechnology. One of the methods includes obtaining a network input comprising an image depicting a plurality of plant cells or regions of plant tissue; processing the network input using a machine learning model to obtain an identification of one or more particular biotechnologically-modifiable plant cells or one or more particular biotechnologically-modifiable regions of the plant tissue; excising or delineating the one or more identified plant cells or the one or more identified regions of the plant tissue; and delivering exogenous material to the excised or delineated plant cells or regions of plant tissue.

Abstract: Methods, devices, and systems for performing digital assays are provided. In certain aspects, the methods, devices, and systems can be used for the detection of nucleic acids and proteins. Also provided are methods, devices, systems, and compositions for improved detection and quantification of target molecules using encoded probes. In certain aspects, the methods, devices, and systems provided herein are useful in multiplexed digital assays. In certain aspects, the methods, devices, and systems can be used for the recognition, detection, and sizing of compartmentalized volumes in a volume. Also provided are compositions and kits suitable for use with the methods and devices of the present disclosure.

Abstract: The present disclosure relates to methods and kits for generating single cell barcodes and imparting them to the constituent molecules within a single cell. Additionally, methods to overlay sample barcode and spatial barcode information onto the single cell barcodes are also described. Generation of single cell barcodes is achieved by labeling the genomic DNA of a cell/nucleus with a small handful, preferably just a one or two cellular barcode probes (CBP) that can be amplified and propagated to label the constituent molecules within the cell. The disclosure finds utility in applications such as characterization of cellular heterogeneity, comprehensive profiling of tissue composition, characterization of adherent cells, discovery of new cell subtypes and functions of individual cells in the context of its microenvironment, and others.

Abstract: The present invention is directed to methods and materials for RNA-mediated gene assembly from oligonucleotide sequences. In some embodiments, the oligonucleotides used for gene assembly are provided in an array format. An RNA polymerase promoter is appended to surface-bound oligonucleotides and a plurality of RNA copies of each oligonucleotide are then produced with an RNA polymerase. These RNA molecules self-assemble into a desired full-length RNA transcript by hybridization and ligation. The resulting RNA transcript may then be converted into double stand DNA useful in a variety of applications including protein expression.

Abstract: The present disclosure provides methods and assay systems for use in spatially encoded biological assays, including assays to determine a spatial pattern of abundance, expression, and/or activity of one or more biological targets across multiple sites in a sample. In particular, the biological targets comprise proteins, and the methods and assay systems do not depend on imaging techniques for the spatial information of the targets. The present disclosure provides methods and assay systems capable of high levels of multiplexing where reagents are provided to a biological sample in order to address tag the sites to which reagents are delivered; instrumentation capable of controlled delivery of reagents; and a decoding scheme providing a readout that is digital in nature.

Abstract: Methods for detecting a chromosomal aneuploidy in a foetus carried by a pregnant female are provided. Such methods are based on one or more of particular configurations and/or detections and/or analyses of two or more regions of DNA, including those that show differential methylation between DNA that originates from cells of a foetus (and/or the placenta of a foetus) and DNA of maternal origin. Such methods utilise a sample taken from a pregnant female, which sample comprises DNA that originates from cells of a foetus and/or the placenta of a foetus in admixture with differently methylated DNA of maternal origin. Such methods have diagnostic, prognostic and/or predictive utility; in particular for the detection/diagnosis of chromosomal aneuploidy, such as a trisomy, in a foetus, and/or for detecting an increased risk of a pregnant female suffering from or developing a pregnancy-associated medical condition.

Abstract: Methods, systems and computer program products for determining a property for a sample having a target region using ultrasound data from an ultrasound scanner include generating at least one spatial coherence curve based on ultrasound backscatter data in the target region, the spatial coherence curve comprising coherence values as a function of depth in the sample; and determining a property for a sample in response to the spatial coherence curve as a function of depth.

Abstract: The present invention generally relates to microfluidics and labeled nucleic acids. In one aspect, the present invention is generally directed to a method, wherein the method includes providing a plurality of droplets comprising particles, the particles comprising oligonucleotides, and attaching a nucleic acid sequence to the oligonucleotides. Certain embodiments are generally directed to systems and methods for splitting a droplet into two or more droplets. Certain embodiments are generally directed to systems and methods for sorting fluidic droplets in a liquid.

Abstract: The invention aims at a non-invasive method of early diagnosis of gastric cancer, using as a biomarker the levels of methylation of the DNA sequence of the promoter of the Reprimo-like gene in plasma. The inventors have established the utility of Reprimo-like as a biomarker, and especially as a biomarker for the early detection of gastric cancer, since they have determined that Reprimo-like is consistently silenced in gastric cancer, both in incipient and advanced stages. This silencing is given by methylation of its promoter region, which is detectable in plasma samples, allowing us to measure it as a liquid biopsy in a non-invasive, fast and inexpensive way.

Abstract: The present invention provides anti-LRP5/6 monoclonal antibodies and related compositions, which may be used in any of a variety of therapeutic methods for treating diseases and disorders associated with Wnt pathway signaling.

Abstract: Disclosed herein are methods for tracking solutions, (e.g., reaction conditions in solutions). In some embodiments, the method comprises: contacting a first lanthanide-chelator complex to a first solution to generate a first barcoded solution, wherein the first lanthanide-chelator complex comprises a first lanthanide chelated by a first chelator; contacting a second lanthanide-chelator complex to a second solution to generate a second barcoded solution, wherein the second lanthanide-chelator complex comprises a second lanthanide chelated by a second chelator; mixing the first barcoded solution and the second barcoded solution to form one or more mixtures; and identifying the first lanthanide ions in the mass spectrum and the second lanthanide ions in the mass spectrum to track the condition of each of the one or more mixtures.

Abstract: The improved Tm mapping method using imperfect-match linear long quenching probes can accurately distinguish among and identify microorganisms at least at the genus level and often at the species level even in a real-time PCR instrument having measurement errors of Tm values between PCR tubes within ±0.5° C. Therefore, the Tm mapping method can be performed in almost all real-time PCR instruments and can identify unspecified infection-causing pathogenic microorganisms in about 4 hours after sample collection.

Abstract: The invention provides an improved stem-loop target capture oligomer and methods of use. Such a target capture oligomer has a target-binding segment forming a loop flanked by stem segments forming a stem. The stem segments are of unequal length. Such probes show little or no binding to immobilized probes in the absence of a target nucleic acid but offer good target sensitivity. The probes are particularly useful in multiplex methods of detection in which multiple target capture oligomers are present for detecting of multiple target nucleic acids (for example, detecting multiple polymorphic forms of a target gene).

Abstract: This disclosure provides new genetic targets, diagnostic methods, and therapeutic treatment regimens for multiple autoimmune disorders, including pediatric autoimmune disorders that are co-inherited and genetically shared. The disclosure, for example, provides methods of diagnosing or determining a susceptibility for one or more autoimmune diseases and methods of determining treatment protocols for patients with one or more autoimmune diseases based on determining if the patients have genetic alterations in particular genes.