Single-Cell Proteomic Technologies: Tools in the quest for principles

TL;DR

This paper reviews recent advances in single-cell proteomic mass spectrometry, emphasizing technological progress, tradeoffs, and the potential for new biological insights and principles.

Contribution

It provides a comprehensive overview of technological developments, tradeoffs, and future directions in single-cell proteomics using mass spectrometry.

Findings

Proteomic analysis of single cells has become robust and scalable.

Technologies support quantification of thousands of proteins per cell.

Potential to develop mechanistic models and uncover new principles.

Abstract

Over the last decade, proteomic analysis of single cells by mass spectrometry transitioned from an uncertain possibility to a set of robust and rapidly advancing technologies supporting the accurate quantification of thousands of proteins. We review the major drivers of this progress, from establishing feasibility to powerful and increasingly scalable methods. We focus on the tradeoffs and synergies of different technological solutions within a coherent conceptual framework, which projects considerable room both for throughput scaling and for extending the analysis scope to functional protein measurements. We highlight the potential of these technologies to support the development of mechanistic biophysical models and help uncover new principles.