Multimodal single-cell proteomics

After a lag phase of skepticism, single-cell proteomics by mass-spectrometry is increasingly gathering speed. It is attracting the interest of colleagues seeking to develop and improve the methods and colleagues seeking to apply the technology to their problems of interest.

The opportunities are beckoning. Which are likely to be the most fruitful and impactful directions? I do not have a crystal ball, but I am more excited for some directions that I will summarize below.  

Empower applications
Current methods allow quantifying > 3,000 proteins across thousands of single cells. We can analyze > 200 single cells / day. These methods are ready to power many applications, and I think all method developers should release detailed protocols to facilitate broad adoption. I think this is a step with a huge marginal benefit. If our experience with the SCoPE2 protocol is indicative, writing a detailed protocol can also be constructive for the team.

Quantifying protein functions: Multimodal single-cell proteomics
The need and opportunities for increasing the depth and accuracy of measuring protein abundances are clear. I am confident that we will see much progress on this front, but I am more excited about harnessing the power of single-cell MS to measure protein functions, not merely abundance. Yes, that is hard. I think it’s also clearly possible and exciting. I alluded to one approach for measuring protein conformations, but there are many other exciting opportunities. Mass-spectrometry analysis of bulk samples affords numerous functional assays and so will single-cell mass-spectrometry analysis. It is up to our creativity to figure out assays for functional multimodal single-cell proteomics, and we will see some examples of those at the Single Cell Proteomics Conference.  

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