Bayesian Nonparametrics for FRET using Realistic Integrative Detectors.

作者信息

Saurabh Ayush, Wisna Gde Bimananda Mahardika, Schweiger Maxwell C, Hariadi Rizal F, Presse Steve

出版信息

bioRxiv. 2025 Aug 27:2025.06.12.659382. doi: 10.1101/2025.06.12.659382.

Abstract

Förster resonance energy transfer (FRET) is a widely used tool to probe nanometer scale dynamics, projecting rich 3D biomolecular motion onto noisy 1D traces. However, interpretation of FRET traces remains challenging due to degeneracy-distinct structural states map to similar FRET efficiencies-and often suffers from under- and/or over-fitting due to the need to predefine the number of FRET states and noise characteristics. Here we provide a new software, Bayesian nonparametric FRET (BNP-FRET) for binned data obtained from integrative detectors, that eliminates user-dependent parameters and accurately incorporates all known noise sources, enabling the identification of distinct configurations from 1D traces in a plug-n-play manner. Using simulated and experimental data, we demonstrate that BNP-FRET eliminates logistical barrier of predetermining states for each FRET trace and permits high-throughput, simultaneous analysis of a large number of kinetically heterogeneous traces. Furthermore, working in the Bayesian paradigm, BNP-FRET naturally provides uncertainty estimates for all model parameters including the number of states, kinetic rates, and FRET efficiencies.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f780/12400910/16bfba50730a/nihpp-2025.06.12.659382v2-f0001.jpg

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