Many pressing medical challenges, such as diagnosing disease, enhancing directed stem-cell differentiation, and classifying cancers, have long been hindered by limitations in our ability to quantify proteins in single cells. Mass spectrometry (MS) is poised to transcend these limitations by developing powerful methods to routinely quantify thousands of proteins and proteoforms across many thousands of single cells. We outline specific technological developments and ideas that can increase the sensitivity and throughput of single-cell MS by orders of magnitude and usher in this new age. These advances will transform medicine and ultimately contribute to understanding biological systems on an entirely new level.
Keywords: Simpson’s paradox; causal inference; counting noise; disease diagnosis; network inference; sample preparation; single-cell analysis; single-cell mass-spectrometry; systems biology; ultrasensitive proteomics.