Advances in mass spectrometry-enabled multiomics at single-cell resolution

Biological organisms are multifaceted, intricate systems where slight perturbations can result in extensive changes in gene expression, protein abundance and/or activity, and metabolic flux. These changes occur at different timescales, spatially across cells of heterogenous origins, and within single cells. Hence multimodal measurements at the smallest biological scales are necessary to capture dynamic changes in heterogenous biological systems. Of the analytical techniques used to measure biomolecules, mass spectrometry has proven to be a powerful option due to its sensitivity, robustness, and flexibility with regards to breadth of biomolecules that can be analyzed. Recently many studies have coupled mass spectrometry to other analytical techniques with the goal of measuring multiple modalities from the same single-cell. It is with these concepts in mind that we focus this Review on mass spectrometry-enabled multiomic measurements at single-cell or near-single-cell resolution.