Abstract

Recently, the throughput of single-cell RNA-sequencing (transcriptomics) and genomics technologies has increased more than a 1000-fold. This increase has powered new analyses: Whereas traditional analysis of bulk tissue averages all differences between the diverse cells comprising such samples, single-cell analysis characterizes each individual cell and thus has enabled the discovery and classification of previously unknown cell states. Yet, the nucleic-acid-based technologies are effectively blind to an important group of biological regulators: proteins. Fortunately, emerging mass-spectrometry (MS) technologies that identify and quantify proteins promise to deliver similar gains to single-cell protein analysis. These proteomic technologies will enable high-throughput investigation of key biological questions, such as signaling mechanisms based on protein binding, modifications, and degradation, that have long remained elusive.