Sampling the proteome by emerging single-molecule and mass spectrometry methods.

Mammalian cells have about 30,000-fold more protein molecules than mRNA molecules, which has major implications in the development of proteomics technologies. We review strategies that have been helpful for counting billions of protein molecules by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and suggest that these strategies can benefit single-molecule methods, especially in mitigating the challenges of the wide dynamic range of the proteome.