Stochastic resonance is behind single cell proteomics success

Abstract

Stochastic resonance is a phenomenon of noise-aided detection of below-threshold signal at the expense of the linearity of signal quantification. Here we demonstrate that peptide signal from single cell proteomes multiplexed by tandem mass tag (TMT) with a carrier proteome is below the nominal detection threshold in the Orbitrap mass analyzer and is registered in the mass spectra largely due to stochastic resonance amplification. This amplification is of the order of 0.5-2.5 single cell equivalents. Consequently, spiking by the corresponding amount of a constant "pedestal" proteome lifts the signal of the analyte single cell proteome above the detection threshold, improving detection and largely restoring linearity of quantification.