Abstract: The present invention relates to a system and method of genomic profiling and is particularly useful in genomic differentiation of heterogeneous and polyclonal neoplastic cell populations, preferably of flow sorted formalin fixed paraffin embedded samples. The present invention includes methods of improving resolution for identifying aberration in variable carcinoma genomes and/or heterogeneous cell populations. The present invention also includes kits configured to improve genomic resolution and the ability to identify genomic aberration in variable and/or heterogeneous cell populations.

Abstract: The disclosed invention is related to methods, compositions and kits for targeting nucleic acid derived from Shiga toxin-producing bacteria such as E. coli. Compositions include amplification oligomers and/or detection probe oligomers. Kits and methods comprise at least one pair of amplification oligomers.

Abstract: Disclosed are a method of determining an HPV integration site in a genome of a human tissue sample and a system thereof. The method comprises: subjecting genome DNA of the human tissue sample to a first sequencing, to obtain a sequencing result; determining DNA fragments containing both HPV sequence and human genome sequence, based on the sequencing result; determining a pair of amplification primers based on the DNA fragments containing both HPV sequence and human genome sequence, subjecting the genome DNA of the human tissue sample to PCR amplification using the pair of amplification primers, to obtain PCR product; and subjecting the PCR product to a second sequencing, to determine the integration site in a genome of the human tissue sample. The method is easy to be operated with low cost, high efficiency and excellent repeatability, which may be used to detect all HPV genotypes one time, and may rapidly and accurately determine detailed sequence information and integration site.

Abstract: The present disclosure provides methods and systems for the capture and enrichment of target nucleic acids and analysis of the enriched target nucleic acids for detecting balanced chromosomal aberrations including translocations and inversions. The present disclosure provides for the enrichment of targeted sequences in a format whereby one fusion partner gene on a capturing platform is represented to allow subsequent sequencing of chimeric nucleic acids (i.e., nucleic acid strands that carry information on different DNA regions of a genome). Such a design enables identification of novel fusion partner genes occurring as a result of a chromosomal translocation or inversion.

Abstract: Methods and systems are presented herein to distinguish children with Autism Spectrum Disorders (ASD) from those with other forms of developmental delay (DD) based on patterns of gene expression levels in blood.

Abstract: A method for detecting biomarkers of prostate cancer or other medical condition of the prostate based on the use of microvesicles obtained from urine samples, and the nucleic acids present in the microvesicles. The method disclosed herein are advantageous in that they may be used to support diagnosis, prognosis, monitoring, or therapy selection in lieu of or in conjunction with traditional biopsy-based diagnostics and do not require a digital rectal examination or prostate massage prior to urine sample collection.

Abstract: Methods and systems are presented herein to distinguish children with Autism Spectrum Disorders (ASD) from those with other forms of developmental delay (DD) based on patterns of gene expression levels in blood.

Abstract: Methods, libraries, and kits for nucleotide sequencing are provided.

Abstract: The present invention relates to a method for the in vitro diagnosis or prognosis of breast cancer, which includes a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said nucleic acid sequences, once isolated, as one or more molecular marker(s) and a kit including at least one specific binding partner of at least one of the expression products of the HERV nucleic acid sequences.

Abstract: Phosphorylation of histones was observed at certain tyrosine residues which have not been associated with epigenetic modification. These sites include H2B Tyr37, H4 Tyr88 and Tyr 51 and H3 Tyr99. Kinases responsible for the phosphorylation as well as downstream genes regulated by such phosphorylation were also identified. Antibodies that are specific to such phosphorylated histones have been generated, which are useful for detecting the phosphorylation and related events. With such findings, the present disclosure provides compositions and methods for disease diagnosis, prognosis and therapy selection, in particular for cancer, obesity and diabetes.

Abstract: The invention is directed to treatment of systemic DNA mutation diseases accompanied with development of somatic mosaicism and elevation of blood extracellular DNA. The inventive method comprises introducing a DNASE enzyme into the systemic blood circulation of a patient in doses and regimens which are sufficient to decrease average molecular weight of circulating extracellular blood DNA in the blood of said patient.

Abstract: In various embodiments, the present invention relates generally to analysis of complex mixtures and, more specifically, to detection and quantitative determination of multiple proteins, protein modifications, and protein-nucleic acid interactions in those complex mixtures.

Abstract: Engineered nucleases (e.g., zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and others) are promising tools for genome manipulation and determining off-target cleavage sites of these enzymes is of great interest. We developed an in vitro selection method that interrogates 1011 DNA sequences for their ability to be cleaved by active, dimeric nulceases, e.g., ZFNs and TALENs. The method revealed hundreds of thousands of DNA sequences, some present in the human genome, that can be cleaved in vitro by two ZFNs, CCR5-224 and VF2468, which target the endogenous human CCR5 and VEGF-A genes, respectively. Analysis of the identified sites in cultured human cells revealed CCR5-224-induced mutagenesis at nine off-target loci. Similarly, we observed 31 off-target sites cleaved by VF2468 in cultured human cells.

Abstract: Disclosed are methods and compositions for detection and amplification of nucleic acids, wherein two DNA strands hybridized to an RNA strand are ligated. In one aspect, the disclosed methods include removal of an energy source, such as ATP, upon charging a ligase to form an enzyme-AMP intermediate, and then adding substrate, which results in one complete round of RNA-templated DNA ligation. In another aspect, the ligation reaction is accomplished by use of a mixture of at least two different ligase enzymes. The disclosed methods and compositions for RNA-templated DNA ligation may be particularly useful for detection of RNA sequence variants, for example RNA splice variants, and for quantitative expression analysis.

Abstract: Provided herein aremethods, compositions and kits for the generation of bisulfite-converted next generation sequencing (NGS) libraries. The methods, compositions and kits provided herein can be useful, for example, for the production of libraries from genomic DNA that allow for determination of the methylation status across the genome, i.e. the methylome. The methods, compositions and kits provided herein can also be utilized to query methylation status at a particular genomic locus or loci. Moreover, the methods provided herein can be employed for high-throughput sequencing of bisulfite-converted DNA while maintaining the directional (strandedness) information of the original nucleic acid sample.

Abstract: Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.

Abstract: The present invention relates to a method of using nanopores to obtain sequence information of sample DNAs in ss test DNAs. The method comprises using speed bumps to stall the ss test DNAs in the nanopores at random positions of the ss test DNAs to obtain sequence information of each and every nucleotides of the sample DNAs, and to construct the whole sequences of the sample DNAs. The present invention also relates to identification and/or isolation of test DNAs having desired sequence(s) using nanopore detectors facilitated by speed bump.

Abstract: Although metabolic networks have been reconstructed on a genome-scale, the corresponding reconstruction and integration of governing transcriptional regulatory networks has not been fully achieved. Here such an integrated network was constructed for amino acid metabolism in Escherichia coli. Analysis of ChlP-chip and gene expression data for the transcription factors ArgR, Lrp, and TrpR showed that 19/20 amino acid biosynthetic pathways are either directly or indirectly controlled by these regulators. Classifying the regulated genes into three functional categories of transport, biosynthesis, and metabolism leads to elucidation of regulatory motifs constituting the integrated network's basic building blocks. The regulatory logic of these motifs was determined based on the relationships between transcription factor binding and changes in transcript levels in response to exogenous amino acids. Remarkably, the resulting logic shows how amino acids are differentiated as signaling and nutrient molecules.

Abstract: In various embodiments, the present invention relates generally to analysis of complex mixtures and, more specifically, to detection and quantitative determination of multiple proteins, protein modifications, and protein-nucleic acid interactions in those complex mixtures.

Abstract: Disclosed herein, in certain instances, are methods for the diagnosis, prognosis and determination of cancer progression of a cancer in a subject. Further disclosed herein, in certain instances, are methods for determining the treatment modality of a cancer in a subject. The methods comprise expression-based analysis of non-coding targets and coding targets. Further disclosed herein, in certain instances, are probe sets for use in assessing a cancer status in a subject.

Abstract: Provided herein are methods, processes, systems, machines and apparatuses for non-invasive assessment of genetic variations.

Abstract: Provided here are new methods to identify specific families of mammalian odorant receptors for odorants or aroma, particularly indole and skatole malodors and their use in assays that may be used to discover compounds that modulate (blocking, enhancing, masking or mimicking compounds) their activity. Orphan mouse odorant receptors are identified from olfactory sensory neurons that respond to target compounds. The resulting receptors as well as their human counterparts can be screened in assays against test compounds to confirm their identity as odorant or aroma receptors, particularly malodor receptors and subsequently discover for example modulators that inhibit the perception of the malodor in humans.

Abstract: Disclosed herein are compositions and methods to treat and reduce therapeutic resistance in chronic myelogenous leukemia. Also disclosed herein are methods to generate leukemia stem cell like cells (iLSCs) generated from CML patient-derived iPSCs, and methods for utilizing iLSCs in screens to identify modulators of CML drug resistance and gene targets that underlie CML drug resistance.

Abstract: The invention relates to a method for detecting at least one target molecule and/or product molecule, wherein reaction components are provided in defined regions of a base surface and/or covering device. At least two defined regions with different reaction components are provided, and an amplification reaction is carried out. The invention also relates to a device for carrying out said method.

Abstract: The present disclosure provides methods for diagnosis of interstitial lung diseases (ILDs). The present disclosure provides methods for differential diagnosis of idiopathic pulmonary fibrosis from other ILDs. Compositions and kits useful in carrying out a subject method are also provided.

Abstract: Methods are provided for multiplexed amplification of selected targets and analysis of the amplified targets. In preferred aspects the amplification and analysis take place on the same solid support and preferably in a localized area such as a bead or a feature of an array. Targets are circularized by hybridization to probes followed by ligation of the ends of the target to form a closed circle. The targets are then used as template for extension of an array bound probe resulting in extended probes having multiple copies of the target. The extended probes can then be analyzed. The methods may be used for genotyping, sequencing and analysis of copy number.

Abstract: Methods, assays, compositions and kits for the ligation of short polynucleotides are presented herein. The short polynucleotides are optionally no more than 7 nucleotides in length, and can be as short as 3 or 4 nucleotides in length. The ligation is optionally performed by CV ligase.

Abstract: Compositions and methods are provided for user-specified fine-tuned protein expression levels, by controlling the initiation of protein translation; and a model for analysis of expression. This method of control can be used to vary, tune, and optimize protein production in genetically engineered organisms, cells, or devices.

Abstract: A method of identifying a hydrocarbon system is disclosed A sample from an area of interest is obtained. A first plurality of analyses is used to determine a community structure of an ecology of the sample. A second plurality of analyses is used to determine a community function of the ecology of the sample. The community structure and the community function are used to determine whether the ecology of the sample matches a characteristic ecology of a hydrocarbon system. When the ecology of the sample matches the characteristic ecology, the sample is identified as part of the hydrocarbon system.

Abstract: The invention provides methods of forming a circular template for sequencing a target nucleic acid. The circular template is generated by amplification of a segment of the target nucleic acid with chimeric primers with complementary 5? ends. The circular template has a single nick or gap providing a site for initiation of template-directed extension for sequence analysis. Sequencing of a single template generates reads of alternating segments of the same strand of the target nucleic spaced by primer segments. The different reads of the same strand of the target nucleic acid can be compiled to generate a consensus sequence. Because only one strand of the target nucleic acid is sequenced per reaction, the present method avoids errors introduced by unwittingly combining sequences of both strands of a heteroduplex PCR product.

Abstract: The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences. In particular, the present invention provides methods and compositions for improving the efficiency of sequencing reactions by using fewer labels to distinguish between nucleotides and by detecting nucleotides at multiple detection positions in a target sequence.

Abstract: The present invention provides methods for purifying RNA molecules interacting with an RNA binding protein (RBP), and the use of such methods to analyze a gene expression profile of a cell. The invention also provides sequences of RNA molecules that mediate binding to an RBP, proteins encoded by the sequences, a method of identifying the sequences, and the use of the sequences in a screen to identify bioactive molecules. The invention also provides RNA motifs found among the sequences and compounds that bind the RNA motifs. In addition, the invention provides methods of treating diseases associated with a function of an RNA binding protein.

Abstract: The present disclosure provides methods to detect pests in liquid culture systems for the growth of microalgae. The disclosure further provides methods to treat and control pests in a liquid system and for methods to increase yields of microalgae grown in a liquid culture systems. Methods are provided for the growth, monitoring, treatment and harvesting of microalgae from liquid culture systems.

Abstract: Methods of isolating cells or generating cell lines comprising the step of exposing the cells to signaling probes that produce a signal upon hybridization to a target sequence, as well as methods of quantifying the level of expression of an RNA of interest, methods for identifying genetic recombinational events in living cells and methods of generating a transgenic animal using the isolated cells. Methods for isolating a plurality of cells encoding a plurality of different RNAs associated with a same nucleic acid tag sequence, comprising the step of exposing the cells to a same signaling probe that produces a detectable signal upon hybridization to the same nucleic acid tag sequence, are also provided. Signaling probes and protease probes that form stem-loop structures, three-arm junction structures, and dumbbell structures may be used in the above methods.

Abstract: The invention provides methods for determining copy number of the Y chromosome, including, but not limited to, methods for gender determination or Y chromosome aneuploidy of fetus using maternal samples comprising maternal and fetal cell free DNA. Some embodiments disclosed herein describe a strategy for filtering out (or masking) non-discriminant sequence reads on chromosome Y using representative training set of female samples. In some embodiments, this filtering strategy is also applicable to filtering autosomes for evaluation of copy number variation of sequences on the autosomes. In some embodiments, methods are provided for determining copy number variation (CNV) of any fetal aneuploidy, and CNVs known or suspected to be associated with a variety of medical conditions. Also disclosed are systems for evaluation of CNV of sequences of interest on the Y chromosome and other chromosomes.

Abstract: Methods and compositions disclosed herein generally relate to methods of improving clinical and economic outcomes to address adverse effects related to anesthesia, analgesics, opioids, and inadequate pain relief. Embodiments of the invention relate to the association between genes, specific polymorphisms of genes, and non-genetic factors with inadequate pain relief and anesthesia-, analgesic, and/or opioid-related adverse effects. Embodiments of the invention can be used to determine and manage patient risk factors for development of adverse perioperative effects and can allow for personalized anesthesia and pain management for improvement of pain control and reduction of anesthesia-, analgesic-, and opioid-related adverse outcomes. These methods and compositions apply to non-surgical pain management with opioids.

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 present invention relates to the field of insect pests control, using methods and compositions which comprise of alpha-amylase analogous mutant inhibitors (?AIs). More specifically, the invention provides new ?AIs analogous mutant molecules for controlling insect pests, in particular boll weevils (Anthonomus grandis), partially or totally presenting reduction of the amylolytic activity of the digestive enzymes in the intestinal lumen of the insect. Other aspects of the invention include gene constructs containing the nucleic acid molecules that code for the alpha-amylase inhibitors, heterologous expression methods of the new molecules in the active form, and the use of these molecules for controlling insect pests. The invention also provides analogous synthetic genes optimized for their transformation and expression in plants.

Abstract: Provided herein are kits, compositions and methods for cancer diagnosis, research and therapy, including but not limited to, cancer markers. In particular, the present invention relates to recurrent RNA fusions as diagnostic markers and clinical targets for leukemia.

Abstract: The present invention relates to systems and methods for performing isothermal amplification reactions, in particular, denaturation methods for use in isothermal amplification reactions. An exemplary method may comprise: a) contacting a target nucleic acid with an electrode, wherein the electrode surface has a plurality of first and optionally second nucleic acid primers immobilized thereon, and wherein a target nucleic acid hybridizes to at least one of said first and second nucleic acid primers; b) extending at least one of the first and second primers using a DNA polymerase to form extended target nucleic acids; c) applying positive electrical bias to the electrode such that the extended target nucleic acids anneal to one of the first and second primers; d) extending the target nucleic acid with a DNA polymerase to form amplified target nucleic acid; e) reversing the electrical bias such that the amplified target nucleic acid is denatured from the surface.

Abstract: This document provides methods and materials involved in assessing samples (e.g., cancer cells) for the presence of homologous recombination deficiency (HRD) or an HRD signature. For example, methods and materials for determining whether or not a cell (e.g., a cancer cell) contains an HRD signature are provided. Materials and methods for identifying cells (e.g., cancer cells) having a deficiency in homology directed repair (HDR) as well as materials and methods for identifying cancer patients likely to respond to a particular cancer treatment regimen also are provided.

Abstract: In one embodiment, a device is described. The device includes a material defining a reaction region. The device also includes a plurality of chemically-sensitive field effect transistors have a common floating gate in communication with the reaction region. The device also includes a circuit to obtain respective output signals from the chemically-sensitive field effect transistors indicating an analyte within the reaction region.

Abstract: Provided is a method for detecting DNA methylation based on MspJI cleavage and performing bioinformatics analysis of genomic methylation.

Abstract: A method for determining the presence of multiple nucleotide sequences of interest in multiple samples while preserving the identity of each sample, by contacting the samples with a plurality of probe sets. The probes are designed to indicate the presence of the sequences of interest and the identity of the sample containing the sequence of interest in complex mixtures. Applications of the method include genotyping, expression analysis, and identification of individual species in complex samples. Kits of probe sets for use in the methods are also provided.

Abstract: Compositions, methods, and kits for identifying protein-nucleic acid complexes, particularly DNA topoisomerase II-DNA complexes, are disclosed.

Abstract: This invention is related to nucleic acid sequencing. In particular, the invention relates to manipulative and analytic steps for analyzing and verifying the products of low frequency events.

Abstract: The systems and methods of the invention provide a guided approach to pyrosequencing (i.e., hybrid pyrosequencing). A de novo nucleic acid sequence may compared to a library of possible results and the next nucleotide to be dispensed is selected based on the comparison of the de novo sequence and the library of possible results. In another example, at least the first nucleotide to be dispensed is selected based on a query of a database(s) of non-sequence parameters (e.g., incidence of infection, diagnostic symptoms, sample source) and subsequent dispensations determined based on a comparison of the de novo sequence and the library of possible results (e.g., candidate sequences). The systems and methods of the invention may be performed using a droplet actuator.

Abstract: The present invention provides detection systems and methods for detection of loci and genomic regions in a sample, including mixed samples, using hybridization to an array.

Abstract: The present invention relates to a method for in vitro diagnosis or prognosis of colon cancer, including a step of detecting at least one expression product of at least one HERV nucleic acid sequence, the use of said isolated nucleic acid sequences as a molecular marker/molecular markers, and a kit including at least one specific binding partner for at least one expression product of the HERV nucleic acid sequences.

Abstract: The present invention provides a method of testing a dog to determine the susceptibility of the dog to liver copper accumulation, comprising detecting in a sample the presence or absence in the genome of the dog of one or more polymorphisms selected from: (a) Chr22_3167534 (SEQ ID NO: 144), Chr22_3135144 (SEQ ID NO: 145), Chr20_55461150 (SEQ ID NO: 146), ChrX_120879711 (SEQ ID NO: 147), Chr19_6078084 (SEQ ID NO: 148), Chr15_62625262 (SEQ ID NO: 149), Chr14_39437543 (SEQ ID NO: 150), Chr15_62625024 (SEQ ID NO: 151), Chr3_86838677 (SEQ ID NO: 152), Chr24_4011833 (SEQ ID NO: 153), Chr18_60812198 (SEQ ID NO: 154), Chr10_65209946 (SEQ ID NO: 155), and the CGCCCC repeat at chromosome location 22:3135287; (b) one or more polymorphisms in linkage disequilibrium with a said polymorphism (a); and/or (c) Chr32_38904515 (SEQ ID NO: 156), Chr8_4892743 (SEQ ID NO: 157) and Chr8_4880518 (SEQ ID NO: 158).