Bioanalysis Zone

The single cell proteomics revolution

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benBen Orsburn received his PhD at Virginia Tech (VA, USA) by applying mass spectrometry to solve biological problems. He has held positions at Johns Hopkins (MD, USA), Thermo Fisher Scientific (CA, USA), NIAID (MD, USA) and the National Cancer Institute (MD, USA). He has spent time developing LC–MS methods in over 150 labs around the world and utilizes these skills as the founder of LCMSmethods.org, a volunteer organization that provides validated instrument methods to researchers in an increasingly broad range of application areas. 

This exclusive editorial explores the very recent and exciting developments in the field of single cell proteomics. Is it time to realize the potential of SCoPE-MS?


Over the holidays I started one of my favorite chores, plotting my conference schedule for 2020. Proteomics has grown rapidly over the last decade and keeping up with the newest advances in hardware, methods and software is a constant requirement to delay obsolescence. To assist, there are annual proteomics meetings in nearly every country and in the US it is closer to an impressive and impactful meeting somewhere every month or two. Regardless of where I end up, one thing is certain, single cell proteomics will be a major topic on stage and over coffee (and possibly over a beer or two).  

Single cell proteomics has been a dream for practitioners of the ion selection arts since John Fenn’s lab first described the ionization of proteins and peptides in the 1990s. The whole term ‘proteomics’ can be described the same way, as the name implies a promise we can only recently claim to have fulfilled – collecting at least a little data from all the proteins an organism produces. Where genomics has been measuring every gene or transcript present for a decade or two, the ability to measure the true proteome didn’t become a reality until about 3 years ago. The gap between the first human genome and proteome draft maps? Over a decade. The trick, it turns out, was the successful coupling of three components: A mass spectrometer that was just fast enough, chromatography that was just sophisticated enough and – while often overlooked – data processing algorithms that were just good enough to pull it all together. Improvements in sample handling and protein extraction haven’t hurt, either. I have my own biases, but I consider June 7, 2017 the day proteomics became a reality, when ‘An optimized shotgun strategy for the rapid generation of comprehensive human proteomes’ was published in Cell Systems [1]. The punchline? Near-theoretically complete coverage of the human proteome in around the same amount of instrument time required to perform transcriptomics with RNA-Seq. The method is fast, relatively easy and didn’t even require the purchase of the most expensive mass spectrometer on earth. A fast, mid-tier benchtop system could do the job, realistically opening the proteome to any lab that really wants to measure it.  

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