Single-cell mass-spectrometry detects peptide ions with high sensitivity, but time constraints limit the proteome coverage of current methods. These constraints are not fundamental, and this Perspective outlines ideas how to relax them.
The analysis of a single Hela cell by mass-spec identifies over 60,000 peptide-like features.
However, the number of peptide-like features analyzed by shotgun methods declines steeply with increasing ion accumulation times, and the accumulation times are long for single-cell proteomics methods.
New data acquisition & interpretation methods may enable confident amino acid sequence identification for tens of thousands of peptide-like features that are detected but not identified by current methods. Developing such methods needs the creativity of the mass-spectrometry community; perhaps many of the most fruitful ideas are yet to come. Here are some ideas for future directions: