Abstract: The present invention describes methods for determining the risk that a breast precursor lesion will progress to invasive breast cancer and/or the risk of recurrent non-invasive disease in a patient, comprising detecting the presence and/or level of PAPPA and/or PAPPA functional activity in a breast tissue sample obtained from the patient, wherein if PAPPA is not present, or is present at a reduced amount compared to a control, there is the risk of progression to invasive cancer and/or the risk or recurrent disease. The present invention also enables the chemosensitisation of mitotically delayed breast cancer cells to anti-proliferative agents, preferably anti-mitotic agents, by restoring normal progression through mitosis. In this embodiment a first drug is applied to release breast cancer cells from the mitotic block and, sequentially, a second drug affecting proliferating cells is administered for cancer cell killing.

Abstract: The present invention relates to methods and compositions for tagging, amplifying, purifying, and or characterizing of ribonucleic acid (RNA) in a sample. In particular, methods are provided for preparing RNA from a sample for subsequent analysis.

Abstract: The disclosure provides methods for the use of gene expression measurements to classify or identify neuroendocrine cancer in samples obtained from a subject in a clinical setting, such as in cases of formalin fixed, paraffin embedded (FFPE) samples.

Abstract: Monoclonal neutralizing antibodies are disclosed that specifically bind to the HIV-1 gp41 membrane-proximal external region (MPER). Also disclosed are compositions including the disclosed antibodies that specifically bind gp41, nucleic acids encoding these antibodies, expression vectors including the nucleic acids, and isolated host cells that express the nucleic acids. The antibodies and compositions disclosed herein can be used for detecting the presence of HIV-1 in a biological sample, or detecting an HIV-1 infection or diagnosing AIDS in a subject. In additional, the broad neutralization breadth of the disclosed antibodies makes them ideal for treating a subject with an HIV infection. Thus, disclosed are methods of treating and/or preventing HIV infection.

Abstract: Methods are provided for determining a risk of age-related macular degeneration (AMD), including a risk of a subject developing AMD or a risk of a subject progressing to an advanced form of AMD based on the detection of rare variants in C3, C9, and CFI.

Abstract: Species of human-derived bacteria belonging to the Clostridia class have been shown to induce accumulation of regulatory T cells (Treg cells) in the colon and suppress immune functions. Pharmaceutical compositions containing these bacteria can be used to prevent and treat immune-mediated diseases such as autoimmune diseases.

Abstract: New mutations were found in exon 19 of the EGFR gene, the exon that is often mutated in tumors. The invention comprises methods of detecting the mutations, methods of prognosis and methods of predicting response to treatment based on the presence of absence of the mutations.

Abstract: The present invention relates to methods for assessing the risk of a patient for developing a potentially fatal cardiac dysrhythmia and for diagnosing Andersen's Syndrome. A tissue sample from a patient is obtained and the DNA or proteins of the sample isolated. From the DNA and protein isolates the sequence of the KCNJ2 gene or the Kir2.1 polypeptide can be obtained. The KCNJ2 gene or the Kir2.1 can be screened for alteration as compared to the wile-type sequence. An alteration in a copy of the KCNJ2 gene or a Kir2.1 polypeptide indicates that the patient has a high risk for developing a cardiac dysrhythmia and can be diagnosed with Andersen's Syndrome. The invention also related to isolated nucleic acid molecules with one or more alterations as compared to the wild-type sequence.

Abstract: A method having steps of (a) providing nucleic acids having a tag sequence (N1)n(N2)n . . . (Nx)n, wherein N1, N2 and Nx are nucleotides that complement different nucleotides, respectively, wherein n is an integer that can differ for N1, N2 and Nx; (b) detecting the nucleic acids individually and under conditions to distinguish signal intensities for (N1)n sequences having different values for n, (N2)n sequences having different values for n and. (Nx)n sequences having different values for n; and (c) distinguishing the tags based on the signal intensities.

Abstract: The disclosure provides a method of identifying a subject as having B-cell non-Hodgkin lymphoma (NHL) such as testing a sample from a subject for a mutation in one or more biomarkers. Also described are methods of classifying or monitoring a subject having, or suspected of having, B-cell non-Hodgkin lymphoma comprising testing the same for a mutation in one or more biomarkers.

Abstract: A nucleic acid amplification method includes ligating a double-stranded adapter (20) containing adapter DNA strands capable of forming a folded structure to a double-stranded DNA (1, 2) containing a target DNA sequence (1) to prepare a cyclic DNA template composed of double-stranded DNA containing a nick (5). A 3?-end elongation reaction is performed using a strand-displacement DNA polymerase from the nick (5) as an origin, thereby producing a concatemer (29) in which a plurality of the target DNA sequences (1) and the adapter DNA strands capable of forming the folded structure are linked in series as a single-stranded DNA. The concatemer (29) contains a plurality of the target DNA sequences (1) suitable for nucleotide sequence analysis and has a folded shape such that it takes the form of a ball due to its folded structure.

Abstract: Provided is a novel method of isolating and producing human antibodies with desired specificity from human B cells. In particular, a method of isolating human antibodies from memory B cells obtained from patients which suffer from a disease which is caused by or involves activation of the immune system, for example autoimmune and inflammatory disorders is described.

Abstract: The invention is a method of detecting or assessing solid organ graft (transplant) rejection by detecting donor-specific HLA alleles in a blood sample of a graft (transplant) recipient. The invention further comprises a method of detecting the presence of maternal cells in a blood sample of an offspring.

Abstract: The invention is directed to methods for biometrically identifying or distinguishing biological specimens, such as patient specimens, as being from the same or different individuals by analysis of specimen clonotypes. The invention provides a direct or backup method for determining or confirming specimen identities. In one aspect, a method of the invention includes generating a first clonotype profile from a first specimen and forming therefrom an identifier set of clonotypes, which serves as a molecular fingerprint of the first specimen. Other specimens are determined to be from the same source individual or from a different source individual by generating clonotype profiles from such specimens and determining the presence or absence in such profiles of clonotypes of the identifier set of the first specimen.

Abstract: Provided in part herein are genetic variations (e.g., single nucleotide polymorphisms) associated with a vascular endothelial growth factor (VEGF) suppression response to an anti-VEGF agent for treatment of a macular degeneration disorder (e.g., age-related macular degeneration (AMD)). Also provided herein are methods for determining a genotype that includes such genetic variations, methods for predicting a VEGF suppression response for a subject according to a genotype, and methods for selecting a treatment suitable for treating a macular degeneration disorder (e.g., wet AMD) for a subject in need thereof according to a genotype.

Abstract: The present disclosure provides methods for determining the ploidy status of a chromosome in a gestating fetus from genotypic data measured from a sample of DNA from the mother of the fetus and from the fetus, and from genotypic data from the mother and optionally also from the father. The ploidy state is determined by using a joint distribution model to create a set of expected allele distributions for different possible fetal ploidy states given the parental genotypic data, and comparing the expected allelic distributions to the pattern of measured allelic distributions measured in the mixed sample, and choosing the ploidy state whose expected allelic distribution pattern most closely matches the observed allelic distribution pattern. In an embodiment, the mixed sample of DNA may be preferentially enriched at a plurality of polymorphic loci in a way that minimizes the allelic bias.

Abstract: The invention relates to methods for pairwise sequencing of a double-stranded polynucleotide template, which methods result in the sequential determination of nucleotide sequences in two distinct and separate regions of the polynucleotide template. Using the methods of the invention it is possible to obtain two linked or paired reads of sequence information from each double-stranded template on a clustered array, rather than just a single sequencing read from one strand of the template.

Abstract: The invention relates to a method for determining the sequence and/or quantity of a ribonucleic acid in a composition, comprising the steps of: i. providing a composition comprising one or more ribonucleic acids molecules (RNA), ii. hybridizing to said one or more RNAs, one or more two-part nucleic acid hybridization probes, wherein each probe comprises, a. a first nucleic acid molecule with a 3?-tail wherein said tail does not hybridize to an RNA in the composition, b. a second nucleic acid molecule with a 5?-tail wherein said tail does not hybridize to an RNA in the composition, c. wherein said first and said second nucleic acid molecules when and if hybridized to their target RNA lie on one single stranded RNA molecule separated from each other by between 2 and 1000 nucleotides, iii.

Abstract: Methods are provided for determining epimutations in a nucleic acid sequence of a cell.

Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

Abstract: A detection apparatus having a read head including a plurality of microfluorometers positioned to simultaneously acquire a plurality of the wide-field images in a common plane; and (b) a translation stage configured to move the read head along a substrate that is in the common plane. The substrate can be a flow cell that is included in a cartridge, the cartridge also including a housing for (i) a sample reservoir; (ii) a fluidic line between the sample reservoir and the flow cell; (iii) several reagent reservoirs in fluid communication with the flow cell, (iv) at least one valve configured to mediate fluid communication between the reservoirs and the flow cell; and (v) at least one pressure source configured to move liquids from the reservoirs to the flow cell. The detection apparatus and cartridge can be used together or independent of each other.

Abstract: The present invention provides a method for constructing a high-throughput sequencing library, which comprises: fragmenting genomic DNA; end-repairing the DNA fragments; adding a base A to the 3? end of the end-repaired DNA fragments; connecting the DNA fragments having cohesive end A with a methylated adapter; carrying out hybrid capture on the connection products by using specific probes to obtain object fragments; treating the object fragments with bisulfite, to convert non-methylated cytosines to uracils; PCR amplifying the converted object fragments; and separating and purifying the amplification products, wherein the amplification products constitute the high-throughput sequencing library. The present invention also provides a method and an apparatus for identifying methylation information in specified genome regions of a sample.

Abstract: A sequencer device generates basic nucleotide sequence data 30 comprising probe data 34 of a capture probe in the sequencer device 10 and a determined sequence of identifiers 32 of a fragment of nucleic acids captured by the probe. The sequencer device outputs enriched nucleotide sequence data 36 that is enriched with data comprising a reference to a sequence 38 that is expected for the fragment of nucleic acids.

Abstract: Disclosed is a method to achieve digital quantification of DNA (i.e., counting differences between identical sequences) using direct shotgun sequencing followed by mapping to the chromosome of origin and enumeration of fragments per chromosome. The preferred method uses massively parallel sequencing, which can produce tens of millions of short sequence tags in a single run and enabling a sampling that can be statistically evaluated. By counting the number of sequence tags mapped to a predefined window in each chromosome, the over- or under-representation of any chromosome in maternal plasma DNA contributed by an aneuploid fetus can be detected. This method does not require the differentiation of fetal versus maternal DNA. The median count of autosomal values is used as a normalization constant to account for differences in total number of sequence tags is used for comparison between samples and between chromosomes.

Abstract: To form a layer separating two volumes of aqueous solution, there is used an apparatus comprising elements defining a chamber, the elements including a body of non-conductive material having formed therein at least one recess opening into the chamber, the recess containing an electrode. A pre-treatment coating of a hydrophobic fluid is applied to the body across the recess. Aqueous solution, having amphiphilic molecules added thereto, is flowed across the body to cover the recess so that aqueous solution is introduced into the recess from the chamber and a layer of the amphiphilic molecules forms across the recess separating a volume of aqueous solution introduced into the recess from the remaining volume of aqueous solution.

Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

Abstract: This disclosure provides methods and compositions for tagging long fragments of a target nucleic acid for sequencing and analyzing the resulting sequence information in order to reduce errors and perform haplotype phasing, for example.

Abstract: Provided is a method of detecting method of detecting fusion transcripts in a sample to be analyzed.

Abstract: The present disclosure relates to systems and methods for nucleic acid isolation. In particular, the present disclosure provides systems and methods for isolating nucleic acids from aqueous samples (e.g., blood or urine).

Abstract: Methods of identifying polymorphisms associated with ataxia-ocular apraxia 2 (AOA2), are described. The polymorphisms associated with AOA2 include specific mutations in the senataxin (SETX) gene. Also described are methods of diagnosis of AOA2, as well as methods of assessing an individual for carrier status for AOA2.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The invention provides for aqueous based emulsions containing uniquely labeled cells, enzymes, nucleic acids, etc., wherein the emulsions further comprise primers, labels, probes, and other reactants. An oil based carrier-fluid envelopes the emulsion library on a microfluidic device, such that a continuous channel provides for flow of the immiscible fluids, to accomplish pooling, coalescing, mixing, sorting, detection, etc., of the emulsion library.

Abstract: The present invention provides a set of DETERMINANTS (e.g., genes and gene products) that can accurately inform about the risk of cancer progression and recurrence, as well as methods of their use.

Abstract: The present invention provides methods and systems for sequencing long nucleic acid fragments. In one aspect of the invention, methods, systems and reagent kits are provided for sequencing nucleic acid target sequences. Some embodiments of the methods, systems and reagent kits are particularly suitable for sequencing a large number of fragments, particularly long fragments.

Abstract: The invention relates to a method for the high throughput discovery, detection and genotyping of one or more genetic markers in one or more samples, comprising the steps of restriction endonuclease digest of DNA, adaptor-ligation, optional pre-amplification, selective amplification, pooling of the amplified products, sequencing the libraries with sufficient redundancy, clustering followed by identification of the genetic markers within the library and/or between libraries and determination of (co-)dominant genotypes of the genetic markers.

Abstract: The invention is directed to methods of generating sequence profiles of populations of nucleic acids, whose member nucleic acids contain regions of high variability, such as populations of nucleic acids encoding T cell receptors or B cell receptors. In one aspect, the invention provides pluralities of sets of primers for generating nested sets of templates from nucleic acids in such populations, thereby insuring the production of at least one template from which sequence reads are generated, despite such variability, or despite limited lengths or quality of sequence reads. In another aspect, members of such populations are bidirectionally sequenced so that further sequence information is obtained by analyzing overlapping sequence reads in the zones of highest variability.

Abstract: Molecular probes to particular targets may be nucleic acids that may generally possess resistance to degradation when bound to a target molecule. For example, the molecular probes may be generally resistant to nuclease degradation when bound to their target molecules, and generally not resistant to nuclease degradation when unbound to their target molecules. This may be utilized, for example, to selectively degrade unbound molecular probes while preserving the bound molecular probes, which may thus serve as an indication of the presence of their target molecules in a sample.

Abstract: The present invention is directed to methods and compositions for the use of micro sphere arrays to detect and quantify a number of nucleic acid reactions. The invention finds use in genotyping, i.e. the determination of the sequence of nucleic acids, particularly alterations such as nucleotide substitutions (mismatches) and single nucleotide polymorphisms (SNPs). Similarly, the invention finds use in the detection and quantification of a nucleic acid target using a variety of amplification techniques, including both signal amplification and target amplification. The methods and compositions of the invention can be used in nucleic acid sequencing reactions as well. All applications can include the use of adapter sequences to allow for universal arrays.

Abstract: The presently disclosed subject matter relates to methods and compositions for identifying, selecting, and/or producing drought tolerant maize plants or germplasm. Maize plants or germplasm that have been identified, selected, and/or produced by any of the methods of the presently disclosed subject matter are also provided.

Abstract: Methods for the high-throughput analysis of transgenic events are herein disclosed. The methods use libraries of sheared genomic DNA ligated to specialized adapters and pooled for sequence analysis and comparison to known genomic and insert sequence. The method finds use in detecting characterizing insertion site, transgene integrity, and transgene copy number.

Abstract: Disclosed are methods for synthesizing and/or assembling at least one polynucleotide product having a predefined sequence from a plurality of different oligonucleotides. In exemplary embodiments, the methods involve synthesis and/or amplification of different oligonucleotides immobilized on a solid support, release of synthesized/amplified oligonucleotides in solution to form droplets, recognition and removal of error-containing oligonucleotides, moving or combining two droplets to allow hybridization and/or ligation between two different oligonucleotides, and further chain extension reaction following hybridization and/or ligation to hierarchically generate desired length of polynucleotide products.

Abstract: The present invention relates to a method for nucleic acid amplification, which enables clusters of amplified nucleic acid fragments to be sequenced by a sequencer to be formed at a high density and improves throughput of nucleic acid sequence analysis by amplifying the number of nucleic acids in the cluster to 10,000 molecules or more; and a method for nucleic acid amplification for enhancing read accuracy, which achieves a high cluster density and increases the number of the amplified fragments in the cluster by the steps of previously forming a pattern of primer DNAs on a base material and fixing bulky template DNA molecules synthesized from DNA samples thereon to induce amplification reaction.

Abstract: Provided is a method of preparing nucleic acid molecules comprising: (a) a step of providing nucleic acid fragments constituting at least a portion of the complete sequence of a target nucleic acid; (b) tagging the nucleic acid fragments with barcode sequences; (c) identifying the sequence of the nucleic acid fragments tagged by the barcode sequences; and (d) recovering desired nucleic acid fragments among the sequence-identified nucleic acid fragments using the barcode sequences.

Abstract: The present invention relates to methods for diagnosing and treating Myhre Syndrome. The invention provides a method for diagnosing or predicting Myhre Syndrome, or a risk of Myhre Syndrome, in a subject, which method comprises detecting a mutation in SMAD4 gene, as compared to a control population, wherein the presence of said mutation is indicative of Myhre Syndrome or of a risk of Myhre Syndrome. The present invention also relates to an inhibitor of the SMAD4-mediated TGF?/BMP signalling pathway for use in the treatment of Myhre Syndrome.

Abstract: Provided are molecular markers for detecting bladder cancer, especially recurrent bladder cancer, and methods of use thereof, including methods of monitoring for the recurrence of bladder cancer.

Abstract: The invention generally relates to rare cell analysis after negative selection.

Abstract: The present invention relates to a high throughput method for the identification and detection of molecular markers wherein restriction fragments are generated and suitable adaptors comprising (sample-specific) identifiers are ligated. The adapter-ligated restriction fragments may be selectively amplified with adaptor compatible primers carrying selective nucleotides at their 3? end. The amplified adapter-ligated restriction fragments are, at least partly, sequenced using high throughput sequencing methods and the sequence parts of the restriction fragments together with the sample-specific identifiers serve as molecular marker.

Abstract: A set of biomarkers (e.g., genes and gene products) that can accurately inform about the risk of cancer progression and recurrence, as well as methods of their use are disclosed.

Abstract: The invention provides methods and compositions, including kits, for directional nucleic acid amplification and sequencing. The invention further provides methods and compositions for the construction of directional cDNA libraries.

Abstract: The present teachings generally relate to fluorescent dyes, linkable forms of fluorescent dyes, energy transfer dyes, reagents labeled with fluorescent dyes and uses thereof.

Abstract: The invention provides methods and reagents for diagnosing colorectal cancer that are based on the detection of biomarkers in the circulating nucleic acids from a patient to be evaluated. In some embodiments, the CNA biomarkers are polynucleotide fragments, e.g., DNA fragments, that are present at an elevated level in blood, e.g., in a serum or plasma sample, of a colorectal cancer patient in comparison to the level in blood, e.g., a serum or plasma sample, obtained from a normal individual who does not have colorectal cancer.