The emerging landscape of single-molecule protein sequencing technologies

Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell profiling. These technologies will in turn facilitate biological discovery and open new avenues for ultrasensitive disease diagnostics. This Perspective describes new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell proteomics.

Automated summary

Single-cell profiling methods have greatly impacted the understanding of cellular heterogeneity, although proteome profiling at the single-cell level is still in the early stages. The development of new technologies, such as single-molecule protein sequencing and innovations in mass spectrometry, will eventually enable broad sequence coverage in single-cell proteomics, leading to new biological discoveries and opportunities for ultra-sensitive disease diagnostics.