Abstract: The present disclosure provides methods for detecting a nucleic acid molecule involving the use of a signal code sequence which corresponds to said nucleic acid molecule, comprising sequential hybridization of detectably labeled probes to allow detection of a signal code sequence. In particular, the present disclosure provides a method of sequential decoding comprising hybridization-directed quenching of detectable moieties that have already been imaged, allowing the newly added probe to be detected without the need to remove the previously imaged detectable moiety, thus providing an approach that reduces or eliminates the need for damaging probe stripping.

Abstract: The present disclosure relates to methods, compositions and systems for droplet processing. For example, methods can include (a) providing a first emulsion comprising a first droplet population, wherein droplets of the first droplet population comprise a lysis reagent, and a second emulsion comprising a second droplet population, wherein a droplet of the second droplet population comprises i) a cell or a nucleus, and ii) a plurality of nucleic acid barcode molecules; (b) subjecting the first emulsion and second emulsion to conditions sufficient to transfer the lysis reagent to the second droplet population via micelles comprising the lysis reagent; and (c) lysing the cell or the nucleus within the droplet of the second droplet population with the lysis reagent.

Abstract: Methods and compositions for analyzing a library comprising a plurality of amplicons comprising identifier sequences are provided, for example, a library of amplicons in a cell or tissue sample attached to a solid support. For example, amplicons are sequenced using a polymerase to incorporate a plurality of cognate nucleotides into the sequencing primer or an extension product thereof to generate a plurality of extension products.

Abstract: In some aspects disclosed herein are methods and compositions for detecting a target nucleic acid molecule, said method comprising performing a linear oligo hybridization chain reaction (LO-HCR) to generate a polymeric product, and detecting the polymeric product, thereby detecting the target nucleic acid molecule.

Abstract: Methods and systems are provided for sample preparation techniques and sequencing of macromolecular constituents of cells and other biological materials.

Abstract: Methods and systems are provided for sample preparation techniques and sequencing of macromolecular constituents of cells and other biological materials.

Abstract: The invention described herein solves challenges in providing a proficient, rapid and meaningful analysis of sequencing data. Methods and computer program products of the invention allow for a system to receive, analyze, and display sequencing data in real-time. The invention provides solutions to several difficulties encountered in assembling short sequencing-reads, and by doing so the invention improves the worth and significance of sequencing data.

Abstract: Provided herein are methods identifying protein-protein interactions in a single cell context. In some cases, the methods may be used to measure the abundance of protein-protein interactions in a single cell context. In some cases, the methods may be used to map relationships (e.g., spatial relationships) between proteins in a single cell context. Generally, the methods employ the use of proximity probes coupled with splint oligonucleotides to link information about the relationship of proteins within a single cell context, which may then be read in a downstream process (e.g., a sequencing reaction).

Abstract: The present disclosure generally relates to methods and compositions for in situ analysis or detection of analytes in a biological sample. More specifically, the present disclosure relates to methods for reducing autofluorescence in tissue samples, methods for analyzing tissue samples, and compounds for use in the same. The methods and compounds of the present disclosure may be especially suitable for analytical methods employing fluorescence in situ hybridization techniques over multiple cycles of imaging.

Abstract: The present application provides methods for detecting a target nucleic acid molecule in a sample comprising contacting said sample with a ligatable probe comprising one or more parts and allowing said probe to hybridise to the target nucleic acid molecule, ligating any probe which has hybridised to the target nucleic acid molecule, amplifying the ligated probe, and detecting the amplification product, thereby to detect the target nucleic acid molecule, wherein said probes comprise at least one ribonucleotide at or near to a ligation site and/or wherein the probe or a probe part comprises an additional sequence 5? to a target-specific binding site which is not hybridised to the target nucleic acid molecule upon hybridisation of the probe to the target nucleic acid molecule and forms a 5? flap containing one or more nucleotides at its 3? end that is cleaved prior to ligation, and methods of synthesising a DNA molecule with Phi29 DNA polymerase using a template nucleic acid molecule comprising at least one ribo

Abstract: Systems and methods for spatial analysis of analytes are provided. A data structure is obtained comprising an image, as an array of pixel values, of a sample on a substrate having a identifier, fiducial markers and a set of capture spots. The pixel values are used to identify derived fiducial spots. The substrate identifier identifies a template having reference positions for reference fiducial spots and a corresponding coordinate system. The derived fiducial spots are aligned with the reference fiducial spots using an alignment algorithm to obtain a transformation between the derived and reference fiducial spots. The transformation and the template corresponding coordinate system are used to register the image to the set of capture spots. The registered image is then analyzed in conjunction with spatial analyte data associated with each capture spot, thereby performing spatial analysis of analytes.

Abstract: In some embodiments described herein are methods performed in situ for analyzing chromatin interaction events in a cell or in cells of a sample such as a non-homogenized tissue sample. The methods can comprise the spatial analysis of chromatin interaction events across cell populations in a biological sample. The methods can further comprise obtaining a biological sample, hybridizing probes to target nucleic acid sequences involved in chromatin interaction events and producing a nucleic acid sequence comprising all or part of the target nucleic acid sequences, amplifying the nucleic acid sequence so produced and detecting the amplified nucleic acid sequence in situ.

Abstract: Provided herein are methods of sequencing comprising click chemistry bioconjugation. In some embodiments, target polynucleotide sequences on the same or different molecules are contacted with and hybridize to probes comprising click functional groups. Probes (e.g., reading probes) hybridizing to adaptor sequences adjacent to different sequences of interest (e.g., barcodes to be sequenced) can be hybridized simultaneously in large pools. In some embodiments, the provided methods achieve multiplexing without requiring separate hybridization of probes (e.g., reading probes) for each sequencing-by-ligation cycle, thereby reducing total hybridization time which is typically a most time-consuming step in in situ technologies. In some aspects, the hybridized probes (e.g., reading probes) are clicked onto detectable probes to analyze a sequence of a target polynucleotide in a sequencing-by-ligation fashion.

Abstract: The present disclosure provides systems and methods that facilitate, at the single cell level, the linking of information from multiple different antibodies (e.g., antibodies specific for different proteins) to the genomic locations of the protein binding sites, while being able to distinguish these distinct events between antibodies.

Abstract: Methods and systems for sample preparation techniques that prevent inhibition of reactions such as due to the presence of longer oligonucleotides are presented herein. The methods and systems provided herein allow amplification (e.g., whole genome amplification) and sequencing of chromatin accessible regions of single cells.

Abstract: In some embodiments, provided herein is an integrated assay of a biological sample comprising an in situ assay module and a spatial assay module. The in situ assay comprises analyzing binding between nucleic acid probes and a first analyte at a spatial location of the biological sample. In some embodiments, the method further comprises providing conditions to allow spatially barcoded capture agents to capture a second analyte for analysis in the spatial assay module.

Abstract: The present disclosure provides systems and methods for processing or analyzing a sample. Methods may include generating supports (e.g., beads) comprising barcode molecules coupled thereto. A support comprising barcode molecules may be useful for analyzing or processing one or more analytes such as nucleic acid molecules, proteins, and/or perturbation agents.

Abstract: The present disclosure relates to methods, compositions and systems for haplotype phasing and copy number variation assays. Included within this disclosure are methods and systems for combining the barcode comprising beads with samples in multiple separate partitions, as well as methods of processing, sequencing and analyzing barcoded samples.

Abstract: Provided herein are compositions, systems and methods for tagging molecular events, reactions, species, etc., but without the need for complex, highly diverse libraries of tagging molecules. Provided are tagging moieties that can have a smaller number, a few, or even a single original “tagging” structure that may be transformed or transformable, in situ, into a collection of larger numbers of unique tagging or “barcode” moieties.

Abstract: Provided herein are methods, compositions, and systems for multiplexed analysis of individual cells or cell populations. Cells encapsulated in beads and/or biomolecules are sequentially co-partitioned, allowing for analysis of two different types of biomolecules (e.g., RNA and DNA). The present invention leverages different polymer dissociation mechanisms, accompanied with barcoding of biomolecules (e.g., nucleic acid molecules) for multiplexed measurements in single cells. Sequential co-partitioning and barcode technology enables identification and quantitation of DNA and RNA from single cells.