Abstract: Biosensors for small molecules can be used in applications that range from metabolic engineering to orthogonal control of transcription. Biosensors are produced based on a ligand-binding domain (LBD) using a method that, in principle, can be applied for any target molecule. The LBD is fused to either a fluorescent protein or a transcriptional activator and is destabilized by mutation such that the fusion accumulates only in cells containing the target ligand. The power of this method is illustrated by developing biosensors for digoxin and progesterone. Addition of ligand to cells expressing a biosensor activates transcription in yeast, mammalian cells and plants, with a dynamic range of up to about 100-fold or more. The biosensors are used to improve the biotransformation of pregnenolone to progesterone in yeast and to regulate CRISPR activity in mammalian cells. This work provides a general methodology to develop biosensors for a broad range of molecules.

Abstract: Methods related to concealment of genetic information present within nucleic acid sequences, wherein individual nucleic acid molecules are barcoded. In some embodiments barcoding occurs before, after, or during enrichment. Barcoded nucleic acids are then combined with control barcoded nucleic acids. Different methods are provided for barcoding and pooling to conceal different types of genetic information present within nucleic acids.

Abstract: The present invention relates to detection molecules comprising at least one binding molecule, at least one linker and at least one label, and detection methods making use of same. The invention provides a high-throughput method for detection, isolation and/or identification of specific entities or cells.

Abstract: A biomarker panel for a urine test for detecting lung cancer detects a biomarker selected from the group of biomarkers consisting of DMA, C5:1, C10:1, ADMA, C5-OH, SDMA, and kynurenine, or a combination thereof. A biomarker panel for a serum test for detecting lung cancer detects a biomarker selected from the group of biomarkers consisting of valine, arginine, ornithine, methionine, spermidine, spermine, diacetylspermine, C10:2, PC aa C32:2, PC ae C36:0, and PC ae C44:5; and lysoPC a C18:2, or a combination thereof.

Abstract: Disclosed herein, inter alia, are methods and compositions for sequencing a plurality of template nucleic acids.

Abstract: Compositions, systems, and methods for preparation of polypeptides having multiple iterations of non-standard amino acids are provided. The compositions and method can be used to produce recombinant proteins at a greater yield than the same or similar polypeptides made using conventional compositions, systems, and methods. Accordingly, in some embodiments, the polypeptides are ones that could not be made using conventional methods and reagents, or could not be made a sufficient yield or purity to serve a practical purpose using conventional methods and reagents. Polypeptides made using the disclosed compositions, systems, and methods are also provided.

Abstract: In some aspects, the present disclosure provides methods for identifying sequence variants in a nucleic acid sample. In some embodiments, a method comprises identifying sequence differences between sequencing reads and a reference sequence, and calling a sequence difference that occurs in at least two different circular polynucleotides, such as two circular polynucleotides having different junctions, or two different sheared polynucleotides as the sequence variant. In some aspects, the present disclosure provides compositions and systems useful in the described method.

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: A Ligand-guided-Selection (LIGS) method for identifying highly specific aptamers against a predetermined antigen of a target is provided. LIGS uses a stronger and highly specific bivalent binder (e.g. an antibody) interacting with its cognate antigen to displace specific aptamers from an enriched SELEX pool. Elution of the displaced aptamers provides aptamers that are specific to the predetermined antigen.

Abstract: Provided herein are methods for making targeted therapeutics. In several embodiments, the therapeutics are directed against soluble agents such as toxins, venoms, and/or other factors that alter physiological biopathways as well as methods of using such therapeutics to treat patients or patient populations to reduce, eliminate, or inactivate, detrimental soluble agents that such patients or patient populations have been exposed to. In several embodiments, the therapeutics are directed to patient-specific disease markers. In several embodiments, the methods comprise screening a library comprising proteins linked to their cognate mRNAs to identify mRNA-protein pairs that bind to the diseased cells, isolating one or more proteins from the identified mRNA-protein pairs, and conjugating the isolated protein(s) to a therapeutic agent.

Abstract: Provided herein are methods of determining a surgical margin and the site and size of a tissue to be resected from a subject, and methods of use thereof.

Abstract: The invention(s) cover a composition, where units of the composition are configured to interact with each other (e.g., as neighbors) in order enable decoding of positions of captured target material relative to neighboring units of the composition. In embodiments, the composition includes: a body; and a set of molecules coupled to the body, the set of molecules comprising a first subset and a second subset, wherein the first subset is structured for target analyte capture, and wherein the second subset is structured for interactions with one or more neighboring objects. The invention(s) also cover systems incorporating one or more units of the composition and methods implementing units of the composition.

Abstract: Diagnostic biomarkers for diagnosing immune suppression/dysfunction. The diagnostic biomarkers are genes and/or transcripts that are up or down regulated compared to normal expression when a subject has been stressed either mentally and/or physically. The invention also relates to a method of detecting comprised or suppressed immune response in a subject by comparing certain diagnostic biomarkers in the subject to a control set of diagnostic biomarkers.

Abstract: A method for developing capture agents for target proteins employs a compound library to find cyclic peptide sequences that bind the target protein. The target protein is also reacted with a clickable group-provider reagent to provide the protein with clickable groups. The compounds in the library are provided with complementary clickable groups that bind the clickable group on the target protein when the peptide sequences bind the target protein. In some embodiments, the cyclic peptide sequences that bind the target protein are incorporated into constructs having one or more arms that can serve as capture agents or potential treatments against the pathogens from which the target protein is derived. Some embodiments provide pharmaceutical compositions for immunoassays, diagnostics, therapeutics or the like, that employ the constructs.

Abstract: This disclosure provides systems and methods for sequencing nucleic acids using nucleotide analogues and translocation of tags from incorporated nucleotide analogues through a nanopore. In aspects, this disclosure is related to compositions, methods, and systems for sequencing nucleic acids using tag molecules and detection of translocation through a nanopore of tags released from incorporation of the molecule.

Abstract: The present disclosure provides a method and systems for processing or analyzing a nucleic acid molecule. A method for processing or analyzing a double-stranded nucleic molecule may comprise providing the double-stranded nucleic acid molecule and a double-stranded adapter. The double-stranded adapter may comprise a nicking site within a sense strand or an anti-sense strand of the double-stranded adapter. The double-stranded adapter may then be coupled to the double-stranded nucleic acid molecule, and the double-stranded nucleic acid molecule coupled to the double-stranded adapter may be circularized to generate a circularized double-stranded nucleic acid molecule.

Abstract: The present invention relates to detection molecules comprising at least one binding molecule, at least one linker and at least one label, and detection methods making use of same. The invention provides a high-throughput method for detection, isolation and/or identification of specific entities or cells.

Abstract: The technology relates in part to methods and compositions for analyzing nucleic acid. In some aspects, the technology relates to methods and compositions for preparing a nucleic acid library. In some aspects, the technology relates to methods and compositions for analyzing ends of nucleic acid fragments.

Abstract: Methods and systems for identifying a protein within a sample are provided herein. A panel of antibodies are acquired, none of which are specific for a single protein or family of proteins. Additionally, the binding properties of the antibodies in the panel are determined. Further, the protein is iteratively exposed to a panel of antibodies. Additionally, a set of antibodies which bind the protein are determined. The identity of the protein is determined using one or more deconvolution methods based on the known binding properties of the antibodies to match the set of antibodies to a sequence of a protein.

Abstract: Disclosed herein, inter alia, are methods and compositions for sequencing a plurality of template nucleic acids.