Embodiments of the present invention relate to analyzing components of a cell. In some embodiments, the present invention relate to analyzing components of a single cell. In some embodiments, the methods and compositions relate to sequencing nucleic acids. In some embodiments, the methods and compositions relate to identifying and/or quantitating nucleic acid, proteins, organelles, and/or cellular metabolites.

Methods of uniquely labeling or barcoding molecules within a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within a cell, a plurality of cells, and/or a tissue are also provided. The molecules to be labeled may include, but are not limited to, RNAs, cDNAs, DNAs, proteins, peptides, and/or antigens.

The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing. Such polynucleotide processing may be useful for a variety of applications, including polynucleotide sequencing. In some cases, this disclosure provides methods for the generation of polynucleotide barcode libraries, and for the attachment of such polynucleotides to target polynucleotides.

Provided herein include methods and compositions for analyzing nucleic acid in individual cells. In some embodiments, the methods herein include generating, within individual cells, fragmented cellular genomic DNA and cDNA copies of cellular RNA molecules, barcoding the fragmented genomic DNA and the cDNA within each cell such that the genomic DNA and the cDNA from the same cell receive the same unique barcode sequence, isolating the barcoded genomic DNA and cDNA, and characterizing one or more features of the individual cells based, at least in part, on sequencing of the isolated barcoded genomic DNA and the cDNA.

Provided herein are methods for preparing and treating an analyte (e.g., a macromolecule or a plurality of macromolecules, peptides, polypeptides, and proteins) for analysis. In some embodiments, the analyte is prepared and treated in a method that includes the use of bait and capture nucleic acids, solid supports, and reaction mixtures including the bait and capture nucleic acids. In some embodiments, the analyte is coupled to a solid support. Also provided are kits containing components for performing the provided methods for preparing the analytes. In some embodiments, the methods are for preparing an analyte for sequencing. Provided herein are methods for preparing and treating an analyte (e.g., a macromolecule or a plurality of macromolecules, peptides, polypeptides, and proteins) for analysis. In some embodiments, the analyte is prepared and treated in a method that includes the use of bait and capture nucleic acids, solid supports, and reaction mixtures including the bait and capture nucleic acids. In some embodiments, the analyte is coupled to a solid support. Also provided are kits containing components for performing the provided methods for preparing the analytes. In some embodiments, the methods are for preparing an analyte for sequencing.

The invention is a novel adaptor containing barcodes for sequencing nucleic acids with a reduced rate of errors.

Provided herein are methods that enable parallel evaluation of multiple functional nucleic acids in individual cells or subpopulations of cells, in the context of incubation with other types of single cells. The key insight is concurrent measurement of polynucleic acids derived from small populations of at least two different cell types, such that function in one cell type is linked to the clonal identity of another cell. These methods simultaneously process thousands, millions, or more single cells or small populations of cells. The method integrates molecular, algorithmic, and engineering approaches. This invention has broad and useful application in a number of biological and medical fields, including immunology and drug discovery.

Cells in a given population often display heterogeneity that may affect how each cell responds to a particular treatment or growth condition. The methods described herein allow determination of which cells from an initial population survive a treatment or condition, and how surviving cells evolve over time. For example, the methods described herein may be used to model drug resistance, response and/or adaptation in a cell population.

Provided herein are methods and compositions for identifying a targeted genomic insertion in a cell. Also provided are heterologous polypeptides that are co-expressed under the control of enodogenous loci and methods of using same.

Provided herein are methods for preparing biological samples for spatial proteomic analysis, methods of determining a location of a protein analyte in a biological sample, and methods of determining a location of a protein analyte and a nucleic acid analyte in a biological sample.