The present invention, among other things, provides technologies for detecting and/or quantifying nucleic acids in cells, tissues, organs or organisms. Through sequential barcoding, the present invention provides methods for high-throughput profiling of a large number of targets, such as transcripts and/or DNA loci. In some embodiments, nucleic acid probes include a signal moiety connected with a binding sequence via a cleavable linker.

The present disclosure relates generally to compositions and methods for high capacity detection of biological samples. Multiple optical labels as well as their combinations, which may include different ratios of the optical labels, can be used to allow detection of a large number of target molecules, cells, or tissues.

The present disclosure relates generally to compositions and methods for high capacity detection of biological samples. Multiple optical labels as well as their combinations, which may include different ratios of the optical labels, can be used to allow detection of a large number of target molecules, cells, or tissues.

Methods and kits for detection of cancer-related mutations are provided, using enzymatic restriction and real-time PCR.

A method for sequencing a population of nucleic acids, which includes (a) binding the population of nucleic acids with a fractionally labeled mixture of nucleotides, thereby forming a fractionally labeled population of nucleic acids, wherein the mixture includes nucleotide cognates for a common base type in the templates, and wherein a fraction of the nucleotide cognates for the common base type in the mixture are exogenously labeled nucleotides that produce a signal that is not produced by other nucleotide cognates for the common base type in the mixture; (b) detecting the signal from the fractionally labeled population of nucleic acids; and (c) repeating (a) and (b) using a second mixture of the fractionally labeled nucleotides, wherein the fraction of the exogenously labeled nucleotides is higher in the second mixture.

Methods and kits for detection of cancer-related mutations in a DNA sample using enzymatic restriction and real-time PCR. A DNA sample is subjected to digestion with a restriction endonuclease to obtain restriction endonuclease-treated DNA, followed by co-amplification of a restriction locus comprising a cancer mutation site and a control locus. A ratio of signal intensities of the amplification products of the restriction locus and the control locus is used to detect the cancer-related mutation.

Methods and kits for detection of cancer-related mutations in a DNA sample using enzymatic restriction and real-time PCR. A DNA sample is subjected to digestion with a restriction endonuclease to obtain restriction endonuclease-treated DNA, followed by co-amplification of a restriction locus comprising a cancer mutation site and a control locus. A ratio of signal intensities of the amplification products of the restriction locus and the control locus is used to detect the cancer-related mutation.

The invention provides compositions and methods for the detection of targets in a sample; in particular, an in situ hybridization (ISH) sample. Probes and detectable labels may be provided in multiple layers in order to increase the flexibility of a detection system, and to allow for amplification to enhance the signal from a target. The layers may be created by incorporating probes and detectable labels into larger molecular units that interact through nucleic acids base-pairing, including peptide-nucleic acid (PNA) base-pairing. Optional non-natural bases allow for degenerate base pairing schemes. The compositions and methods are also compatible with immunohistochemistry (IHC), immunocytochemistry (ICC), flow cytometry, enzyme immuno-assays (EIA), enzyme linked immuno-assays (ELISA), blotting methods (e.g. Western, Southern, and Northern), labeling inside electrophoresis systems or on surfaces or arrays, and precipitation, among other general detection assay formats. The invention is also compatible with many different types of targets, probes, and detectable labels.

The invention provides compositions and methods for the detection of targets in a sample; in particular, an in situ hybridization (ISH) sample. Probes and detectable labels may be provided in multiple layers in order to increase the flexibility of a detection system, and to allow for amplification to enhance the signal from a target. The layers may be created by incorporating probes and detectable labels into larger molecular units that interact through nucleic acids base-pairing, including peptide-nucleic acid (PNA) base-pairing. Optional non-natural bases allow for degenerate base pairing schemes. The compositions and methods are also compatible with immunohistochemistry (IHC), immunocytochemistry (ICC), flow cytometry, enzyme immuno-assays (EIA), enzyme linked immuno-assays (ELISA), blotting methods (e.g. Western, Southern, and Northern), labeling inside electrophoresis systems or on surfaces or arrays, and precipitation, among other general detection assay formats. The invention is also compatible with many different types of targets, probes, and detectable labels.

Provided herein are methods for improved polynucleotide detection.