Protocol to identify proteins as regulators of gene expression noise.

Noise regulatory proteins are key to understanding the dynamic regulation of cell-to-cell heterogeneity in gene expression. Here, we present a protocol for identifying novel candidate proteins with noise regulatory functions. We describe steps for inhibiting translation in cells, performing single-cell RNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS), and utilizing known regulator-target interactions to integrate obtained data in a regulator enrichment analysis. This protocol has the potential to be applied in any cell line and under culture conditions of choice. For complete details on the use and execution of this protocol, please refer to García-Blay et al.(1).