Methods for protein identification through combinatorial barcoding

Abstract

Methods and kits for assessing and partially or uniquely identifying proteins, such as in complex mixtures of proteins and other molecules/structures, are described. In an embodiment, the methods include combinatorially barcoding target amino acid residues on the protein and, in certain embodiments, enzymatically cleaving the protein, such as before and after rounds of combinatorial barcoding. In an embodiment, the methods include (a) attaching a first nucleic acid molecule to target amino acid residues in the plurality of proteins in the sample to provide nascent nucleic acid tags at the target amino acid residues; (b) performing one or more rounds of split-pool barcoding to provide mature nucleic acid tags at the target amino acid residues (c) sequencing the mature nucleic acid tags; and (d) determining a frequency of the target amino acid residues in one or more protein of the plurality of proteins.