Abstract: The present invention relates to improved methods for epigenetic blood and immune cell counting, and respective uses and kits.

Abstract: A method of sequencing nucleic acids is provided using sequencing by ligation and/or sequencing by hybridization.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting DGAT2 expression, which may be useful for treating, preventing, or ameliorating a disease associated with DGAT2.

Abstract: Methods for controlling for non-systematic error in an amplification-based next generation sequencing (NGS) library preparation are described, which method includes using an internal amplification control (IAC) sharing identical priming sites to a native nucleic acid target template of interest in a NGS library preparation.

Abstract: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endonucleases based on the presence or absence of a target mRNA. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

Abstract: Provided are compositions and methods for cleaving a DNA sequence in a cell. The methods involve comprising introducing into a cell a recombinant vector containing a clustered regularly interspaced short palindromic repeats (CRISPR) system. The system includes a CRISPR RNA (crRNA) targeted to a DNA sequence in the cell that is operatively linked to a promoter; and CRISPR-associated enzymes (Cas) 10, Cas6, and at least one Csm protein. The Cas 10 cleaves the DNA sequence only during transcription of the DNA sequence that is operatively linked to the promoter. Also provided are recombinant vectors for modifying cells, cells that contain the recombinant vectors and modifications introduced by them, and kits that include the modified vectors.

Abstract: The present invention relates to a nucleic acid detection kit and a nucleic acid detection method, which use nanoparticles. More specifically, the present invention relates to: a nucleic acid detection method comprising a step of amplifying and labeling nucleic acids, and then capturing the same by using nanoparticles and centrifuging the same; and a nucleic acid detection kit using the method. The present invention is effective since a negative or positive determination for a particular disease can be made, through the nucleic acid detection method not comprising a separation step, in a more rapid, simple, sensitive, and highly reliable manner.

Abstract: The invention relates to a mediator probe comprising a probe region and a mediator region. Furthermore, the invention relates to a system comprising a mediator probe and a detection molecule, use of that system and a method for detection of at least one target molecule.

Abstract: Techniques for measuring sequences of nucleic acids are provided. Time-based measurements (e.g., forming a histogram) particular to a given sequencing cell can be used to generate a tailored model. The model can include probability functions, each corresponding to different states (e.g., different states of a nanopore). Such probability functions can be fit to a histogram of measurements obtained for that cell. The probability functions can be updated over a sequencing run of the nucleic acid so that drifts in physical properties of the sequencing cell can be compensated. A hidden Markov model can use such probability functions as emission probabilities for determining the most likely nucleotide states over time. For sequencing cells involving a polymerase, a 2-state classification between bound and unbound states of the polymerase can be performed. The bound regions can be further analyzed by a second classifier to distinguish between states corresponding to different bound nucleotides.

Abstract: The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.

Abstract: Analytical standards can allow one to detect and/or measure sampling, processing, and/or amplification errors in a sample that includes a plurality of polynucleotide molecules. The analytical standards can provide an internal control to detect errors in the representation of the original sample reflected in data obtained after manipulating and/or processing of sample molecules.

Abstract: Provided herein is a method for sequencing a polynucleotide molecules. The method includes the steps of providing a plurality of polynucleotide molecules attached to a surface, wherein a first portion of each polynucleotide molecule is attached to a first location of the surface and a second portion of each polynucleotide molecule is attached to a second location of the surface, the relative proximity of the first and second locations being correlated with the probability that the first and second portions are paired, separating the first and second portions of the polynucleotide molecules on the surface, determining the sequences of the first and second portions of the polynucleotide molecules and comparing the relative proximities and the sequences to determine which first and second portions are paired and to determine the sequence of the target polynucleotide molecules.

Abstract: The present disclosure provides methods, kits, and compositions for generating DNA molecules encoding CRISPR/Cas guide RNAs (e.g., Cas9 single guide RNAs or Cas9 targeter RNAs). A library of such DNA molecules can be generated from any DNA source. The methods include a step of contacting target DNA with one or more DNA endonucleases that specifically bind to and cleave within a recognition sequence that includes a PAM sequence, to generate a plurality of cleavage fragments, to which a DNA adapter can be attached. A distal-cleaving DNA endonuclease can be used that specifically binds to a recognition sequence in the DNA adapter and cleaves at a site within the attached DNA cleavage fragments to generate a library of CRISPR/Cas guide sequences. After removal of all or a portion of the DNA adapter, a constant region of a guide RNA can be attached to generate DNA molecules encoding CRISPR/Cas guide RNAs.

Abstract: Novel oligonucleotides that are fully chemically stabilized are provided. Methods of using oligonucleotides that are fully chemically stabilized are also provided.

Abstract: A primer set includes a terminal primer A including, in its 3?-terminal part, a nucleotide sequence that hybridizes to a 3?-terminal part of a complementary sequence of a first target nucleic acid sequence, a k-th double-headed primer including two polynucleotides linked at their 5? terminal sides, wherein one of the two polynucleotides includes, in its 3?-terminal part, a nucleotide sequence that hybridizes to a 3?-terminal part of a nucleotide sequence of a k-th target nucleic acid, and the other polynucleotide includes, in its 3?-terminal part, a nucleotide sequence that hybridizes to a 3?-terminal part of a complementary sequence of a (k+1)th target nucleic acid, and a terminal primer B including, in its 3?-terminal part, a nucleotide sequence that hybridizes to a 3?-terminal part of a nucleotide sequence of a N-th target nucleic acid.

Abstract: The present invention relates to compositions and methods for increasing the rate of nuclease-mediated site specific insertions of donor DNA sequence to the genome via recombination. More specifically, the method utilizes a non-naturally occurring nuclease-homology directed repair (HDR) protein chimeras for genome editing applications. Physically tethering the activity of a DNA nuclease to an HDR protein results in significant increase in the fraction of nuclease induced DNA breaks that are repaired by homologous recombination and provides higher accuracy and specificity of genome editing.

Abstract: The invention provides methods for generating pools of variants of DNA templates, and methods of using pools of variants to identify sequences involved in conferring sensitivity or resistance to environmental factors.

Abstract: The invention generally relates to capturing, amplifying, and sequencing nucleic acids. In certain embodiments, copies of the sense and antisense strands of a duplex template nucleic acid are captured using linked capture probes and multiple binding and extension steps to improve specificity over traditional single binding target capture techniques. Methods of seeding sequencing clusters with sense and antisense strands of a target nucleic acid are also disclosed including identifying the strands using sense-specific barcodes and confirming base calls using two sense-specific sequencing reads. Linked adapters may be used to increase adapter ligation selectively or efficiency and yield.

Abstract: Disclosed herein, inter alia, are compounds, compositions, and methods of use thereof in the sequencing a nucleic acid.

Abstract: High throughput personal genomic testing has created a need for robust quality control mechanisms to track sample identity, reagent integrity, and other factors with significant influence on assay performance. A method of massively parallel sequencing using an accompanying barcoded molecular standard enables one to track nucleic acid analytes to identify them by project, lot, batch, or patient. The molecular standard contains sequences present in the analyte, allowing it to be processed simultaneously without any other additional reagents. Within the molecular standard, a calibrator sequence permits assessment of fidelity of sequence determination. Additional sequences in the molecular standard may be used to manipulate the molecular standard separate from the analyte. The molecular standard can be used to benchmark sequencing platforms and assess error rates.

Abstract: Methods and compositions for the detection and quantification of nucleic acids are provided. In certain embodiments, methods involve the use of primers or probes that comprise a non-natural nucleotide linked to a reporter. Target nucleic acids are detected by the polymerization of a complementary probe or primer that incorporated a cognate non-natural nucleotide linked to a quencher.

Abstract: The present disclosure relates to methods of treating EPAS1-related diseases such as cancer, metastases, astrocytoma, bladder cancer, breast cancer, chondrosarcoma, colorectal carcinoma, gastric carcinoma, glioblastoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, neuroblastoma, non-small cell lung cancer, melanoma, multiple myeloma, ovarian cancer, rectal cancer, renal cancer, clear cell renal cell carcinoma (and metastases of this and other cancers), gingivitis, psoriasis, Kaposi's sarcoma-associated herpesvirus, preeclampsia, inflammation, chronic inflammation, neovascular diseases, and rheumatoid arthritis, using a therapeutically effective amount of a RNAi agent to EPAS1.

Abstract: Methods, compositions, and kits are provided for CRISPR/Cas mediated transcriptional modulation.

Abstract: This document provides methods and materials for assessing RNA expression. For example, methods and materials for detecting the presence, absence, or amount of target nucleic acid (e.g., target RNA or target cDNA produced from target RNA), kits for detecting the presence, absence, or amount of target nucleic acid (e.g., target RNA or target cDNA produced from target RNA), and methods for making such kits are provided.

Abstract: The invention relates, in part, to systems and methods for scoring a sample containing tumor tissue from a cancer patient. The score is representative of a nearness between at least one pair of cells, a first member of the least one pair of cells expressing a first biomarker and a second member of the at least one pair of cells expressing a second biomarker that is different from the first biomarker. The score obtained from these methods can be indicative of a likelihood that a patient may respond positively to immunotherapy.

Abstract: CRISPR/CAS-related compositions and methods for treatment of Sickle Cell Disease (SCD) are disclosed.

Abstract: The present invention is directed to methods for reducing cross-reactivity between species employed in multiplexed immunoassays.

Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Abstract: The present invention relates to a microfluidic device to manipulate, select, treat, or cultivate living bodies, comprising a first chamber, a second chamber and a network of guiding tracks, wherein: said network of guiding tracks comprises at least one first guiding track connecting the first chamber and the second chamber and at least one second guiding track connecting said at least one first guiding track with at least two interconnections; and said at least one second guiding track comprises a curved part; said curved part exhibiting a concavity facing the second chamber or the part of the network connected to the second chamber.

Abstract: Disclosed are methods of diagnosing and treating metastatic cancer in a subject. The methods involve detecting or modulating the expression of at least one of Kif3b, ACTB, SRPK1, TM EM 229b, Cl4orf142, KB-1460A1.5, ACTC1, Nr2f1, KIAA0922, KDELR3, APBA2, miRNA 130b, miRNA 374b, or miRNA 122 in a biological sample from the subject.

Abstract: Provided herein are compositions and methods for detecting the binding of a peptide to an MHC molecule, and the binding of a peptide:MHC complex to a TCR. In preferred embodiments, the compositions and methods are in a highly-multiplexed way. The compositions and methods disclosed herein can be used to provide direct information on which peptides are bound to an MHC molecule. Also provided is a method for simultaneously detecting a large number of peptides for binding to an MHC molecule and/or a T cell. A method for detecting competitive binding of a large number of peptides to an MHC molecule and/or a T cell is also disclosed. Also provided herein is a method for simultaneously detecting a large number of specific TCRs. The compositions and methods of the present invention are useful for vaccine design, research and monitoring of autoimmune and infectious disease, immunogenicity testing of therapeutics, and tissue typing.

Abstract: A method of trapping constituents of interest in a fluid sample flowing through a microfluidic channel by vibrating an interface of the fluid sample and a gas occupying a lateral channel adjacent the microfluidic channel is described. A marker is flowed into the microfluidic channel such that the marker bonds with constituents of interest. The constituents of interest bonded to the marker can help identification of the constituents of interest.

Abstract: The present invention relates to the selection of patients with enhanced antipsychotic treatment efficacy with iloperidone based on a patient's genotype at one or more single nucleotide polymorphism (SNP) loci and to treatment of such patients based upon the identification of their genetic information.

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 assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

Abstract: The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR ? chain, TCR ? chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

Abstract: The present disclosure provides a Cas9 heterodimer, as well as nucleic acids encoding the Cas9 heterodimer, and host cells comprising the nucleic acids. The present disclosure provides a system that includes a Cas9 heterodimer of the present disclosure and at least one of: a Cas9 guide RNA, and a dimerizing agent. A Cas9 heterodimer of the present disclosure is useful in a wide variety of applications, which are also provided.

Abstract: This disclosure relates to the field of secondary metabolite production in plants. More specifically, the disclosure relates to chimeric genes encoding a bHLH protein of subfamily Iva comprising a bHLH domain and their use in the regulation of biosynthesis and/or production of secondary metabolites in plants and plant-derived cell cultures.

Abstract: The invention relates to improved RNA compositions for use in therapeutic applications. The RNA compositions are particularly suited for use in human therapeutic application (e.g., in RNA therapeutics). The RNA compositions are made by improved processes, in particular, improved in vitro-transcription (IVT) processes. The invention also relates to methods for producing and purifying RNA (e.g, therapeutic RNAs), as well as methods for using the RNA compositions and therapeutic applications thereof.

Abstract: Modulation of microRNAs against myotonic dystrophy type 1 and antagonists of microRNAs therefor. The invention provides the use of inhibitors of microRNAs repressors of MBNL1 and/or MBNL2 genes for the manufacture of a medicinal product for the treatment of myotonic dystrophy 1. Inhibiting these microRNAs allows to increase the endogenous levels of the corresponding proteins MBNL1 and/or MBNL2, thereby alleviating symptoms of the disease, especially when inhibiting repressors that are expressed in the main affected organs: skeletal muscle, heart or organs of the central nervous system. The inhibition of the microRNAs miR-23b-3p and miR-218-5p is preferred. It also provides oligoribonucleotide or oligoribonucleotide analogue antagonists suitable therefor, preferably antagomiRs directed against the microRNAs mentioned with chemical modifications that enhance their interaction with the target, their stability in vivo and their ability to penetrate into the cells and distribute throughout tissues and organs.

Abstract: The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR ? chain, TCR ? chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

Abstract: A method is provided comprising the following steps: (a) treating a nucleic acid with bisulfite to convert non-methylated cytosines in the nucleic acid into uracils while leaving methylated cytosines unchanged to form a treated nucleic acid strand that is part of two joined nucleic acid strands; (b) ligating a first adapter to a 3? end of the treated nucleic acid strand, the first adapter having a first protruding random sequence that least 3 bases long and that acts as a splint for the two joined nucleic acid strands; (c) ligating a second adapter to a 5? end of the once adapter ligated nucleic acid strand, the second adapter having a second protruding random sequence at least 3 bases long and that acts as a splint for the two joined nucleic acid strands; and (d) performing PCR amplification on the twice ligated nucleic acid strand.

Abstract: The invention provides compositions comprising nucleic acid complexes for use in monitoring binding interactions and in measuring association and/or dissociation kinetics, detecting analytes including low concentration analytes, and screening library members. In some instances, the nucleic acid complexes are double-stranded nicked nucleic acids comprising a scaffold nucleic acid hybridized to one or more oligonucleotides. In some instances, a first, a second, a third, and optionally a fourth oligonucleotide are linked to moieties that are known to interact with each other or which are suspected of interacting with each other or of interacting with a common moiety such as an analyte. Changes in topology of the complex are used to determine the binding interactions of the various binding partners.

Abstract: The present disclosure provides nucleic acid molecules, and kits comprising the same, for producing templated assembly products for a cell.

Abstract: The present invention relates to a biomarker and uses thereof for liver cancer diagnosis or prognosis prediction. The biomarker according to the present invention may be used as a marker for liver cancer diagnosis and prognosis prediction with improved specificity and sensitivity. Thus, the biomarker may be used not only to diagnose or prognose liver cancer with high accuracy and reliability, but also to effectively screen a liver cancer treatment agent.

Abstract: An electrochemical system for cancer diagnosis. The electrochemical system includes a sensor configured to be put in contact with a sample suspected to be cancerous, an electrochemical stimulator-analyzer, a processor electrically connected to the electrochemical stimulator-analyzer, and an array of electrically conductive connectors connecting the sensor to the electrochemical stimulator-analyzer.

Abstract: The present invention relates to methods for shifting the splicing profile of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding U7-based small nuclear RNAs to induce DUX4 exon-skipping and the expression of shortened forms of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

Abstract: An electrochemical probe for in-vivo measurement of H2O2 oxidation within a living tissue. The electrochemical probe includes a sensing part and a handle. The sensing part includes a working electrode including a first biocompatible conductive needle, a counter electrode including a second biocompatible conductive needle, and a reference electrode including a third biocompatible conductive needle. The working electrode, the counter electrode, and the reference electrode are configured to be put in contact with the living tissue by inserting the sensing part into the living tissue. The handle includes an insertion part that may be configured to insert the sensing part into the living tissue. The sensing part is attached to the insertion part.

Abstract: A pressure regulator module for a chip-based microfluidic platform is provided. The module includes a microfluidic channel for passing flowable material from the inlet region through the outlet region and into a downstream compartment; one or more microvalves fluidly connected to the microfluidic channel and upstream of the outlet region; and one or more reservoirs fluidly connected to the microvalves, for receiving flowable material diverted by the microvalves, where a flow of flowable material passing from the inlet region toward the downstream compartment is at least partially diverted by the microvalves into the reservoirs as a result of a pressure increase in the microfluidic channel. In some versions, the microvalves are capillary burst valves. A microfluidic chip containing the module and a method of using the module are provided.

Abstract: Provided are devices, systems, and methods for the identification, quantification, and profiling of microscopic organisms. The methods for the identification, quantification, and profiling of microscopic organisms include, for example, the selective enrichment of microscopic organisms from a heterogeneous sample; subsequent loading of the microscopic organisms into microfluidic channels or reaction chambers; direct amplification of nucleic acids from single, isolated microscopic organisms; and examination of amplification products using digital High Resolution Melting (HRM) analysis.