Normalize both fluorescent reporter intensities by their respective means, correcting unequal brightness and background, and denote them . Extrinsic gene-expression noise changes shared cellular conditions and moves both signals together: the scatter is a long narrow cloud around . Intrinsic gene-expression noise comes from distinct random expression events in the two genes and broadens the cloud across that diagonal. Comparable contributions therefore give a noticeably wider, still positively correlated cloud. The two right-hand panels in the preceding original illustration show these two cases.
For matched fluorescent reporters with conditionally independent intrinsic fluctuations and corrected measurement noise,The first quantity measures differential variation; the second measures common variation. A clone's successive observations can remain correlated in time, so they need not be independent samples. Shared activation transients should also be separated from the fluctuations of interest.[ref]
Stochastic Gene Expression in a Single Cell by Michael B. Elowitz and others. Science 297 (2002), pp. 1183–1186: dual-reporter discrimination of intrinsic and extrinsic variation
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