Abstract: The present invention provides method of classifying a subject into a necrotizing meningoencephalitis (NME) disease risk group. The method may include assessing the presence of one or more marker (e.g., SNPs or risk loci) in a sample from the subject. For example, detection of the presence of one or more markers that are associated with an increased risk of NME can indicate that the subject should be classified into a risk group.

Abstract: Disclosed herein are methods, compositions and kits for quantitating one or more specific nucleic acids within a plurality of nucleic acids. In some embodiments, a sequencing library is constructed from enriched probe extension products specific for the specific nucleic acids and sequenced. In some embodiments, the resulting reads are used for removing duplicate reads. In some embodiments, counting of verified probes is used to quantitate or determine the number of specific nucleic acid molecules in the starting nucleic acid sample.

Abstract: The invention relates to a method for identifying one or more polymorphisms in nucleic acid samples, comprising: (a) performing a reproducible complexity reduction on a plurality of nucleic acid samples to provide a plurality of libraries of the nucleic acid samples comprising amplified fragments, wherein the reproducible complexity reduction comprises amplifying fragments of the nucleic acid samples using one or more primers to obtain the amplified fragments, and wherein the amplified fragments in each library comprise a unique identifier sequence to indicate origin of each library obtained by the reproducible complexity reduction; (b) combining the plurality of libraries to obtain a combined library and sequencing at least a portion of the combined library to obtain sequences; (c) aligning the sequences to obtain an alignment; and (d) identifying one or more polymorphisms in the plurality of nucleic acid samples.

Abstract: 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.

Abstract: 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.

Abstract: The present invention relates to an anti-NMDA antibody or fragment or derivative thereof which is effective in inhibiting the deleterious effects of tissue-type plasminogen activator (t-PA) mediated by N-methyl-D-aspartate (NMDA) receptors and to medical uses, in particular for the treatment of neurological or neurodegenerative disorders, e.g. multiple sclerosis.

Abstract: A method for the prevention or treatment of scoliosis in a human subject comprising: (a)(i) measuring osteopontin (OPN) protein expression in a biological fluid sample from the subject over time; or (ii) measuring osteopontin (OPN) protein expression in a biological fluid sample from the subject and comparing the OPN protein expression to an OPN protein expression in a control biological fluid sample; (b) identifying the subject as being at risk of developing scoliosis when OPN protein expression increases in the subject sample over time; or when OPN protein expression is higher in the subject sample than that in the control sample; and (c) reducing OPN protein levels in the subject identified as being at risk of developing a scoliosis, thereby aiding in the prevention or treatment of scoliosis.

Abstract: The present invention provides a method for determining P1/P2 blood type, including steps of providing a biological sample of a subject, detecting a genotype for single nucleotide polymorphism rs2143918 or rs5751348 in A4GALT gene of the biological sample and determining a phenotype of the subject based on the genotype. Further, the present invention also provides a kit for determining P1/P2 blood type, including a primer pair for detecting a genotype for single nucleotide polymorphisms rs2143918 or rs5751348 in A4GALT gene of a nucleic acid sample of a subject.

Abstract: Provided herein is technology relating to detecting neoplasia and particularly, but not exclusively, to methods, compositions, and related uses for detecting premalignant and malignant neoplasms such as pancreatic and colorectal cancer. Accordingly, provided herein is technology for pancreatic cancer screening markers and other gastrointestinal cancer screening markers that provide a high signal to-noise ratio and a low background level when detected from samples taken from a subject (e.g., stool sample). As described herein, the technology provides a number of methylated DNA markers and subsets thereof (e.g., sets of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more markers) with high discrimination for G1 neoplasms overall and/or at individual tumor sites.

Abstract: A semiconductor structure is provided that can be used for DNA sequencing detection. The semiconductor structure includes a doped epitaxial source semiconductor material structure located on a first portion of a semiconductor substrate and a doped epitaxial drain semiconductor material structure located on a second portion of the semiconductor substrate. A gate dielectric portion is located on a third portion of the semiconductor substrate and positioned between the doped epitaxial source semiconductor material structure and the doped epitaxial drain semiconductor material structure. A non-stick nucleotide, DNA and DNA polymerase material structure is located atop the doped epitaxial source semiconductor material structure and atop the doped epitaxial drain semiconductor material structure, wherein a cavity is present in the non-stick nucleotide, DNA and DNA polymerase material structure that exposes a topmost surface of the gate dielectric portion.

Abstract: Provided herein is technology relating to detecting neoplasia and particularly, but not exclusively, to methods, compositions, and related uses for detecting premalignant and malignant neoplasms such as pancreatic and colorectal cancer.

Abstract: Systems, apparatus, and methods are provided for determining genetic or molecular aberrations in a biological sample. Biological samples including cell-free DNA fragments are analyzed to identify imbalances in chromosomal regions, e.g., due to deletions and/or amplifications in a tumor. Multiple loci are used for each chromosomal region. Such imbalances can be used to diagnose (screen) a patient for cancer, as well as prognosticate a patient with cancer, or to detect the presence or to monitor the progress of a premalignant condition in a patient. Severity of an imbalance and the number of regions exhibiting an imbalance can be used. A systematic analysis of non-overlapping genomic segments can provide a general screening tool. A patient can be tested over time to track severity of each of one or more chromosomal regions and a number of chromosomal regions to enable screening and prognosticating, as well as monitoring of progress (e.g. after treatment).

Abstract: The invention generally relates to methods for distinguishing a rare genetic variation in a nucleic acid sequence.

Abstract: The present invention provides a method and a reagent for enrichment of circulating tumor DNA, the method comprising the steps of mixing a water phase and an oil phase and shaking the mixture to prepare an emulsion PCR reaction system, and performing emulsion PCR amplification, wherein the water phase comprises peripheral blood plasma DNA as template DNA, a forward primer and a reverse primer, dNTPs, a PCR buffer and a DNA polymerase, the peripheral blood plasma DNA having adapter sequences connected to both ends thereof, and the forward primer and the reverse primer being complementary to the adapter sequences at the two ends respectively; separating the water phase from the oil phase following the emulsion PCR amplification to obtain a PCR amplification product in the water phase; and capturing circulating tumor DNA in the PCR amplification product in the water phase by using a probe sequence that specifically binds to the circulating tumor DNA.

Abstract: The disclosure provides methods to assemble genomes of eukaryotic or prokaryotic organisms. The disclosure further provides methods for haplotype phasing and meta-genomics assemblies.

Abstract: A sol-gel deposition technique that forms ion sensitive layers is compatible with CMOS fabrication methods and is applied to build sensors of concentrations of solutions of selected target ions. The ion sensitive sensor may be formed on an exposed portion of a signal trace of a printed circuit board. Additionally, the ion sensitive layer may be formed within an ion sensitive field effect transistor.

Abstract: Various molecular barcoded bi-stable switches are provided that can be used to detect various analytes. An electrical current is provided through a pore to electrophoretically draw at least a portion of one or more molecular barcoded bi-stable switches from one volume through one or more pores to another volume. Each molecular barcoded bi-stable switch includes a status identifier that provides an indication when a binding material is bound to the analyte. Each molecular barcoded bi-stable switch also includes a barcode that can be read as it passes through the pore to ascertain the identity of the particular molecular barcoded bi-stable switch.

Abstract: Disclosed are methods and tools for rapidly aligning reads to a reference sequence. These methods and tools employ Bloom filters or similar set membership testers to perform the alignment. The reads may be short sequences of nucleic acids or other biological molecules and the reference sequences may be sequences of genomes, chromosomes, etc. The Bloom filters include a collection of hash functions, a bit array, and associated logic for applying reads to the filter. Each filter, and there may be multiple of these used in a particular application, is used to determine whether an applied read is present in a reference sequence. Each Bloom filter is associated with a single reference sequence such as the sequence of a particular chromosome. In one example, chromosomal abundance is determined by aligning reads from a sequencer to multiple chromosomes, each having an associated Bloom filter or other set membership tester.

Abstract: The invention relates to a method of identifying VDJ recombination products which comprises the use of sequence specific enrichment and specific restriction endonuclease enzymes or other DNA-shearing approaches to provide high resolution and high throughput interrogation of antigen receptor repertoires.

Abstract: The present invention provides a method of identifying mRNA transcripts in the transcriptome of a cell comprising i) delivering into the cell a donor expression vector comprising nucleotides in a sequence encoding a trans-splicing barcode cassette, ii) exposing the cell to conditions such that the cell produces multiple copies of the trans-splicing barcode cassette encoded by the donor expression vector, which multiple copies of the trans-splicing barcode cassette each splice the barcode polynucleotide onto a mRNA transcript of the cell, thereby forming multiple mRNA transcripts of the cell, each spliced to the barcode polynucleotide; and iii) identifying the multiple mRNA transcripts that are spliced to the barcode polynucleotides, thereby identifying mRNA transcripts in the transcriptome of the cell.

Abstract: The present disclosure generally relates to sequencing two or more genes expressed in a single cell in a high-throughput manner. More particularly, the present disclosure relates to a method for high-throughput sequencing of pairs of transcripts co expressed in single cells (e.g., antibody VH and VL coding sequence) to determine pairs of polypeptide chains that comprise immune receptors.

Abstract: In accordance with the teachings described herein, systems and methods are provided for estimating quantiles for data stored in a distributed system. In one embodiment, an instruction is received to estimate a specified quantile for a variate in a set of data stored at a plurality of nodes in the distributed system. A plurality of data bins for the variate are defined that are each associated with a different range of data values in the set of data. Lower and upper quantile bounds for each of the plurality of data bins are determined based on the total number of data values that fall within each of the plurality of data bins. The specified quantile is estimated based on an identified one of the plurality of data bins that includes the specified quantile based on the lower and upper quantile bounds.

Abstract: Provided herein is technology relating to detecting neoplasia and particularly, but not exclusively, to methods, compositions, and related uses for detecting premalignant and malignant neoplasms such as pancreatic and colorectal cancer.

Abstract: The technology described herein is directed to methods of determining oligonucleotide sequences, e.g. by enriching target sequences prior to sequencing the sequences.

Abstract: An antibody-fragment-immobilizing substrate includes a substrate and at least one set of antibody fragments, wherein the antibody fragments of each set includes at least two types of separate antibody fragments that are capable of recognizing one type of antigen and that are independently immobilized on the substrate in a positional relationship that allows each of the antibody fragments in one set to bind to the same antigen.

Abstract: A method of monitoring amplification of a nucleic acid by providing a nucleic acid and an amplification mixture using the kit of isothermal reagents to a pH sensor or pH indicator, amplifying the nucleic acid using isothermal amplification, and detecting a change in pH due to the amplification using the pH sensor or pH indicator. The kit of reagents comprises a magnesium salt, a quaternary ammonium salt, and an alkali base.

Abstract: A device comprising an electrostatic discharge protection structure, an ion sensitive field effect transistor (ISFET) having a floating gate, and a sensing layer located above the floating gate. The device is configured such that the electrical impedance from the sensing layer to the electrostatic discharge protection structure is less than the electrical impedance from the sensing layer to the floating gate. The device can be fabricated in a standard CMOS process.

Abstract: The sensor includes a first graphene film that is provided on the insulating layer so as to be located in a flow path of a liquid containing the detection target substance, the first graphene film having a first edge that is parallel with a first direction that is along the flow path and a first edge that is parallel with a second direction that is different from the first direction, and the first graphene film having the shape of a band that extends in the second direction. The sensor includes a first electrode that is electrically connected to the first edge of the first graphene film that is parallel with the first direction. The sensor includes a second electrode that is electrically connected to a second edge of the first graphene film that is opposed to the first edge that is parallel with the first direction.

Abstract: The present disclosure relates generally to drug discovery and development and, more particularly, to in vitro assay systems and methods for selecting lead anti-cancer agents for subsequent testing in human and non-human subjects. The present disclosure allows filtering for candidate anti-cancer agents that are not inactivated by liver enzymes, are able to diffuse through cell layers, are not toxic to bone marrow cells, retain anti-cancer activity in the context of stromal support, and are effective after time-limited exposure mimicking non-hepatic clearance by kidneys and other mechanisms.

Abstract: Based on our identification of a polypeptide (Angiopep-7) that is efficiently transported to cells such as liver, lung, kidney, spleen, and muscle, the invention provides polypeptides, conjugates including the polypeptides, and methods for treating diseases associated with these cell types. Unlike other aprotinin related polypeptides identified herein (including Angiopep-3, Angiopep-4a Angiopep-4b Angiopep-5, and Angiopep-6) which efficiently cross the blood-brain barrier (BBB), Angiopep-7 is not efficiently transported across the BBB.

Abstract: The invention provides methods for determining the interactions between phage-displayed proteins and test molecules. The phage-displayed proteins are contacted with a reference moiety in the presence and absence of a test molecule; the behavior of the phage-displayed proteins as a function of concentration of the test molecule permits calculation of the binding affinity of the phage-displayed protein for the test molecule.

Abstract: Described herein are methods for diagnosing ovarian cancer. In particular, certain microRNAs are useful to the response to chemotherapy of ovarian cancer patients.

Abstract: Accurate and fast mapping of sequencing reads obtained from a targeted sequencing procedure can be provided. Once a target region is selected, alternate regions of the genome that are sufficiently similar to the target region can be identified. If a sequencing read is more similar to the target region than to an alternate region, then the read can be determined as aligning to the target region. The reads aligning to the target region can then be analyzed to determine whether a mutation exists in the target region. Accordingly, a sequencing read can be compared to the target region and the corresponding alternate regions, and not to the entire genome, thereby providing computational efficiency.

Abstract: The invention, in some aspects relates to synthetic, light-activated fusion proteins and their encoding polynucleotide molecules. In some aspects the invention additionally includes expression of the light-activated fusion proteins in cells and their use in methods such as therapeutic methods and candidate compound screening methods.

Abstract: A method of sample analysis is provided. In certain embodiments, the method involves: a) obtaining a fragmented RNA sample comprising fragments of long RNA molecules and short RNA molecules; b) ligating an adaptor to an end of the RNA of the fragmented RNA sample to produce an adaptor-ligated sample; c) hybridizing said adaptor-ligated sample to an array of nucleic acid probes; and d) reading said array to obtain an estimate of the abundance of a long RNA in the RNA sample and an estimate of the abundance a small RNA in the RNA sample.

Abstract: Described herein are methods useful for incorporating one or more adaptors and/or nucleotide tag(s) and/or barcode nucleotide sequence(s) one, or typically more, target nucleotide sequences. In particular embodiments, nucleic acid fragments having adaptors, e.g., suitable for use in high-throughput DNA sequencing are generated. In other embodiments, information about a reaction mixture is encoded into a reaction product. Also described herein are methods and kits useful for amplifying one or more target nucleic acids in preparation for applications such as bidirectional nucleic acid sequencing. In particular embodiments, methods of the invention entail additionally carrying out bidirectional DNA sequencing. Also described herein are methods for encoding and detecting and/or quantifying alleles by primer extension.

Abstract: This invention provides methods of derivatizing a double-stranded DNA comprising contacting double-stranded DNA with a CpG methyltransferase and an s-adenosylmethionine analog. This invention also provides methods of sequencing DNA to determine methylation patterns.

Abstract: The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of splitting a droplet is provided, the method including providing a droplet microactuator including a droplet including one or more beads and immobilizing at least one of the one or more beads. The method further includes conducting one or more droplet operations to divide the droplet to yield a set of droplets including a droplet including the one or more immobilized beads and a droplet substantially lacking the one or more immobilized beads.

Abstract: The present disclosure generally relates to sequencing two or more genes expressed in a single cell in a high-throughput manner. More particularly, the present disclosure relates to a method for high-throughput sequencing of pairs of transcripts co expressed in single cells (e.g., antibody VH and VL coding sequence) to determine pairs of polypeptide chains that comprise immune receptors.

Abstract: The invention relates to a method for enriching one or more target sequences of a deoxyribonucleic acid (DNA) in a composition, comprising the steps of providing a composition comprising one or more deoxyribonucleic acid (DNA) molecules, hybridizing to said one or more DNA molecules, one or more target specific ribonucleic acid (RNA) hybridization probes, thereby forming one or more RNA/DNA hybrids, capturing the RNA/DNA hybrids with one or more antibodies being specific for such RNA/DNA hybrids, thereby forming one or more RNA/DNA/antibody hybrids, isolating the one or more RNA/DNA/antibody hybrids, amplifying the one or more DNA molecules of the one or more RNA/DNA/antibody hybrids if necessary, and, optionally, sequencing the one or more DNA molecules of the one or more RNA/DNA/antibody hybrids or the amplification product, wherein the sequencing is preferably done by means of next generation sequencing.

Abstract: The invention provides a method for in-field detection of a distinctive marker. The method includes providing a sample from an article of interest and analyzing the sample to detect the presence of the distinctive marker. The analysis is performed using an in-field detection instrument. The in-field detection instrument includes a microsystem configured to perform sample in-answer out analysis and detect the presence of the distinctive marker in the sample.

Abstract: Different combinations of methylation status based biomarkers can be used to test for breast cancer with high sensitivity and high specificity.

Abstract: This invention relates generally to composition and methods for characterizing a methylome which comprises all or substantially all methylation states of a genome. In particular, a plurality of oligonucleotides, each representing nearly every possible methylation state of the cytosine position of each CG dinucleotide pair within a target nucleic acid of interest, and methods of using the plurality are provided herein.

Abstract: This invention provides methods of using circulating diseased cells in the diagnosis, prognosis, or monitoring of diseases or conditions. The invention also provides methods of using circulating diseased cells to identify markers of diseases or conditions. This invention also provides methods for assessing the risk of developing a disease or condition, prognosing said disease, monitoring said disease progression or regression, assessing the efficacy of a treatment, or identifying a compound capable of ameliorating or treating said disease or condition.

Abstract: The present invention is a novel protocol for the massively parallel production of improved MIPs. The molecular improvements to the MIP cover the manufacturing of the probes, the workflow, the addition of unique sequence elements which connote sample specificity, and a sequence tag which uniquely identifies a specific molecule present in the initial sample population. Lastly, this invention also is combined with an empirical optimization strategy that overcomes issues of both locus representation and allelic bias. This improved technique is scalable and can be utilized to amplify targets comprised of a single locus' amplicon up to targeting more than 1 million loci.

Abstract: The present disclosure relates to methods of determining a treatment course of action. In particular, the present disclosure relates to mutations in the gene encoding estrogen receptor and their association with responsiveness to estrogen therapies for cancer.

Abstract: The present disclosure describes methods, devices, reagents, and kits for the detection of one or more target molecules that may be present in a test sample. The described methods, devices, kits, and reagents facilitate the detection and quantification of a non-nucleic acid target (e.g., a protein target) in a test sample by detecting and quantifying a nucleic acid (i.e., an aptamer) where the aptamer-aptamer interactions are significantly reduced or eliminated while maintaining the aptamer-target interaction.

Abstract: The invention relates to methods and compositions that enable the rapid generation of high-order combinations of genetic elements, and that provide a barcoded basis for rapid characterization of the specific combination of genetic elements encoded within a single cell or in a pooled population.

Abstract: The present invention relates to compositions and methods useful for analyzing lariat RNA, which plays a role in the regulation of gene expression. A sample of RNA is specifically treated to remove linear mRNA and enrich for lariat RNA. The enriched lariat RNA sample may be analyzed further to identify introns, branch point sequences, alternative splicing patters, and gene transcription levels. The enriched lariat RNA sample may also be exploited as a detection or compound screening tool, as well as other uses.

Abstract: Provided is a method for monitoring a gene mutation associated with a cancer in a patient over time. Also provided is a method of selecting and/or applying treatment or therapy for a subject.