Single-Cell Protein Profiling by Microdroplet Barcoding and Next-Generation Sequencing

DNA barcoding of individual cells combined with next-generation sequencing enables high-throughput parallel analysis of biomolecules at the single-cell level. Encoding protein identity with DNA barcoding of specific antibody binders achieves sequencing-based protein quantitation by converting protein signals into DNA signals. Here, we describe how to prepare DNA-barcoded antibodies and connect protein identities to cellular identities using droplet microfluidics. This approach allows for multiplex single-cell protein analysis compatible with single-cell transcriptomic and mutational profiling methods.