Strategies for Development of a Next-Generation Protein Sequencing Platform

Proteomic analysis can be a critical bottleneck in cellular characterization. The current paradigm relies primarily on mass spectrometry of peptides and affinity reagents (i.e., antibodies), both of which require a priori knowledge of the sample. An unbiased protein sequencing method, with dynamic range that covers the full range of protein concentrations in proteomes, would revolutionize the field of proteomics, allowing a more facile characterization of novel gene products and subcellular complexes. To this end, several new platforms based on single-molecule protein-sequencing approaches have been proposed. This review summarizes four of these approaches, highlighting advantages, limitations, and challenges for each method towards advancing as a core technology for next-generation protein sequencing.