Probe-based analysis of nucleic acids and proteins

A method of analyzing a cell, comprising:

• (a) providing a sample comprising a cell, wherein the cell comprises:
• (i) a feature, wherein the feature comprises a protein, a peptide, a lipid, or a carbohydrate;
• and
• (ii) a nucleic acid molecule;
• and
• (b) contacting the cell with a feature binding group and coupling the feature binding group to the feature, wherein the feature binding group comprises an oligonucleotide comprising a feature nucleic acid sequence that identifies the feature binding group;
• (c) hybridizing a first nucleic acid probe to the nucleic acid molecule;
• wherein the first nucleic acid probe comprises (i) a hybridizing sequence that hybridizes to a first target sequence of the nucleic acid molecule and (ii) a non-hybridizing sequence;
• (d) using the feature nucleic acid sequence and a first barcode molecule comprising a first barcode sequence to generate a first barcoded nucleic acid molecule comprising (i) the feature nucleic acid sequence or reverse complement thereof, and (ii) the first barcode sequence or reverse complement thereof;
• and
• (e) using the non-hybridizing sequence and a second barcode molecule comprising a second barcode sequence to generate a second barcoded nucleic acid molecule comprising (i) the first target sequence or reverse complement thereof and (ii) the second barcode sequence or reverse complement thereof.