Abstract: Described herein are methods, devices, systems, and compositions for detecting a target nucleic acid using a programmable nuclease and a signal amplifier. Such methods, devices, systems, and compositions can comprise using signal amplifiers, such as catalytic oligonucleotides, which can be activated by programmable nucleases and be configured to cleave a reporter molecule upon activation. Signals can be generated and detected upon cleavage of reporter molecules.

Abstract: A method of generating customizable goal representation is disclosed. A request from a user to view a goal representation is received. A flexible goal ontology is accessed that comprises one or more goal entities, one or more goal relationships between the goal entities, or one or more goal properties, the one or more goal properties including one or more metadata attributes relating to the one or more goal entities. A set of mapping rules is obtained that defines mappings between one or more goals. The set of mapping rules is evaluated to assemble a customized goal representation tailored to the user. The customized goal representation is updated based on a revaluation of the mapping rules affected by changes to the one or more goal entities, the one or more goal relationships, or the one or more properties.

Abstract: Provided herein, in certain embodiments, are various methods, reagents, and devices for detection of multiple target nucleic acids in a sample, or multiple segments of a target nucleic acid in a sample, using a programmable nuclease. In certain embodiments, the present disclosure provides compositions of pools of guide nucleic acids, programmable nucleases, and detector nucleic acids and methods of using said compositions for detection of different segments of one target nucleic acid or different target nucleic acids in a sample.

Abstract: A modified nucleoside or nucleotide, the 3?-OH of the modified nucleoside or nucleotide being reversibly blocked; meanwhile, the present invention also relates to a kit comprising the nucleoside or nucleotide, and a sequencing method based on the nucleoside or nucleotide.

Abstract: The present disclosure provides an O-methyltransferase protein with a highly specific catalytic function for multiple benzylisoquinoline alkaloids (BIAs) parent nuclei and an encoding gene and use thereof. Compared with wild-type O-methyltransferase, the O-methyltransferase protein (SEQ ID NO: 2) shows an enhanced enzymatic activity and a wider substrate scope. The O-methyltransferase protein can catalyze O-methylation of backbones from three BIAs, including monobenzylisoquinolines (norcoclaurine, coclaurine, and N-methylcoclaurine), aporphines (asimilobine and N-methylasimilobine), and protoberberines (scoulerine and tetrahydrocolumbamine). Meanwhile, this O-methyltransferase protein is highly regioselective for each backbone. The O-methyltransferase protein catalyzes methylation of the monobenzylisoquinolines at 6-OH and 7-OH, is only active on 6-OH of the backbone of the aporphines, and mainly catalyzes methylation of the protoberberines at 2-OH.

Abstract: The disclosure provides for CRISPR-Cas-based detection of SARS-CoV-2 using recombinase polymerase amplification, and uses thereof.

Abstract: The present disclosure provides compositions and methods of use for Type V CRISPR/Cas proteins. Type V CRISPR/Cas nucleases may be configured to bind nucleic acids in a sequence specific manner. Such a binding event may activate the Type V CRISPR/Cas nuclease for sequence non-specific trans-collateral cleavage of single-stranded nucleic acids. Provided herein are methods leveraging Type V CRISPR/Cas nuclease trans-collateral cleavage for identifying nucleic acid sequences.

Abstract: Described herein, in certain embodiments, are methods of assaying for a segment of a coronavirus target nucleic acid in a sample. In some embodiments, the target nucleic acid is from a gene of SARS-CoV-2, or a variant thereof. In some embodiments, methods described herein comprise a) contacting the sample to: i) a detector nucleic acid; and ii) a composition comprising a programmable nuclease and a non-naturally occurring guide nucleic acid, and b) assaying for a change in a signal, wherein the change in the signal is produced by cleavage of the detector nucleic acid by the programmable nuclease. Also provided herein are devices for performing the methods of assaying for a segment of a coronavirus target nucleic acid described herein.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: The present invention relates to the field of plant genetic engineering. In particular, the present invention relates to acetolactate synthase (ALS) mutants, protoporphyrinogen oxidase (PPO) mutants, acetyl-CoA carboxylase (ACCase) mutants and/or p-hydroxyphenylpyruvate dioxidase (HPPD) mutants capable of conferring herbicide resistance in plants, especially in wheat and/or rice plants, and methods for production herbicide-resistant plants, especially wheat and/or rice plants comprising said acetolactate synthase (ALS) mutants and/or protoporphyrinogen oxidase (PPO) mutants and/or acetyl-CoA carboxylase (ACCase) mutants and/or p-hydroxyphenylpyruvate dioxidase (HPPD) mutants.

Abstract: The disclosure provides methods for characterizing a target DNA present in a sample. The methods involve contacting the sample with one or more universal primers to amplify target DNA; contacting the amplified target DNA with a type V CRISPR/Cas effector protein and one or more guide RNAs, where the contacting generates a cleavage product comprising a 5? overhang; and ligating a double-stranded nucleic acid adapter to the cleavage product, to generate a ligation product. The ligation product includes the target DNA, which can be sequenced. The sample can be subjected to one or more amplification steps prior to the contacting step, with primers that provide for amplification of nucleic acids of, e.g., specific pathogens, categories of pathogens, two or more different pathogens, or two or more different categories of pathogens.

Abstract: Disclosed herein are systems and methods for providing a high-throughput DETECTR assay in a single chamber. The single chamber may be one well of a microplate, and multiple assays may be conducted in a staggered fashion in separate chambers. The methods described herein implement a process including lysing a sample, isolating nucleic acid molecules, eluting the nucleic acid molecules, amplifying the nucleic acid molecules, and detecting a presence of a target nucleic acid.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Described herein are methods and systems for direct detection of DNA nucleic acids using a DNA-activated programmable RNA nuclease.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids.

Abstract: Described herein are methods to detect nucleic acid modifications, such as methylated DNA or methylated RNA, using a programmable nuclease. The present disclosure further provides compositions and methods for generating and amplifying ssDNA from target nucleic acid sequences, or templates, for activation of programmable nucleases. Further provided herein are methods of coupling ssDNA amplification and activation of programmable nucleases with programmable nuclease systems, such as DETECTR systems, including trans cleavage of detector nucleic acids to produce a signal indicating the presence of the target nucleic acid sequence.

Abstract: Disclosed herein are compositions, kits, and methods related to improved Cas activity. Through compositions and kits disclosed herein and practice of methods disclosed herein, one attains improved Cas activity such as Cas12 activity relative to Cas proteins in the art such as LbCas12. Further described herein are methods to detect target nucleic acid using a programmable nuclease system. Often, the target nucleic acids are present in at low frequency in the sample. Provided herein are methods for enriching these target nucleic acids for detection. Also described herein are methods to insert a PAM sequence into a target sequence of interest for use in a detection comprising a programmable nuclease.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.

Abstract: Described herein are devices, systems, fluidic devices, kits, and methods for detection of target nucleic acids associated with diseases, cancers, genetic disorders, a genotype, a phenotype, or ancestral origin. The devices, systems, fluidic devices, kits, and methods may comprise reagents of a guide nucleic acid targeting a target nucleic acid, a programmable nuclease, and a single stranded detector nucleic acid with a detection moiety. The target nucleic acid of interest may be indicative of a disease, and the disease may be communicable diseases, or of a cancer or genetic disorder. The target nucleic acid of interest may be indicative of a genotype, a phenotype, or ancestral origin.