The common misuse of noise decomposition as applied to genetic systems

The noise-decomposition technique is applied in several fields, including genetic systems, optical images, recording, and navigation. In genetic systems, noise decomposition is usually achieved by using two reporters [Elowitz M.B., Levine A.J., Siggia E.D., Swain P·S., 2002. Stochastic gene expression in a single cell. Science 297, 1183-6.]. A reporter is a protein with fluorescence, an RNA hybridized with a fluorescent probe, or any other detectable intracellular component. If a reporter is constructed in addition to the original reporter, the system's stochasticity may change. Such phenomena became severe for genes in plasmids with a high copy number. By SSA (stochastic simulation algorithm), we observed an approximately 50% increment in the coefficient of variation while introducing additional reporters. Besides, if two reporters respond to the upstream element at a different time, the trunk noise (or extrinsic noise) cannot be accurately determined. This is because the "calculative trunk noise" changes along with the delay, though the real trunk noise does not. For RNA reporters, a 5-min transcriptional delay caused a calculative trunk noise that was 90% less than the real trunk noise. Fortunately, this problem is negligible when the degradation rate constant is low, and it is usually true in the case of the protein reporters. One can check the lifespan of the reporter before applying the noise-decomposition technique.