Signal-to-noise ratio (SNR) limits what we can learn from data. In fluorescence microscopy, SNR is set by the number of photons acquired from a sample and the efficiency with which these photon are used in data analysis. Experimental configurations that determine the former tend to be highly optimized, whereas analysis methods to maximize the latter remain comparatively underexplored. This is the case for intensity-based, time-lapse fluorescence resonance energy transfer (FRET) microscopy, a powerful method for quantifying the dynamics of molecular interactions inside cells. Here, we develop an information-theoretically optimal method to estimate molecular interaction from such FRET data that maximizes SNR. Like bright fluorescent proteins and sensitive photodetectors, the method expands the scope of FRET microscopy by significantly improving SNR.

PNAS
The Netherlands Organisation for Scientific Research (NWO)
doi.org/10.1073/pnas.2211807120
PNAS
Systems Biology

Kamino, K, Kadakia, N, Avgidis, F, Liu, Z.X, Aoki, K, Shimizu, T.S, & Emonet, T. (2023). Optimal inference of molecular interaction dynamics in FRET microscopy. PNAS, 120(15), e2211807120: 1–e2211807120:12. doi:10.1073/pnas.2211807120