TY - JOUR
T1 - Single-photon smFRET. I
T2 - Theory and conceptual basis
AU - Saurabh, Ayush
AU - Fazel, Mohamadreza
AU - Safar, Matthew
AU - Sgouralis, Ioannis
AU - Pressé, Steve
N1 - Funding Information:
We thank Weiqing Xu and Dr. Zeliha Kilic for regular feedback and help, especially during the development of the nonparametrics samplers, and Dr. Irina Gopich for discussions. S.P. acknowledges support from the NIH NIGMS (R01GM130745) for supporting early efforts in nonparametrics and NIH NIGMS (R01GM134426) for supporting single-photon efforts. The bulk of the computations was performed on Agave and Sol supercomputers at ASU. The authors declare no competing interests.
Funding Information:
We thank Weiqing Xu and Dr. Zeliha Kilic for regular feedback and help, especially during the development of the nonparametrics samplers, and Dr. Irina Gopich for discussions. S.P. acknowledges support from the NIH NIGMS ( R01GM130745 ) for supporting early efforts in nonparametrics and NIH NIGMS ( R01GM134426 ) for supporting single-photon efforts. The bulk of the computations was performed on Agave and Sol supercomputers at ASU.
Publisher Copyright:
© 2022 The Authors
PY - 2023/3/8
Y1 - 2023/3/8
N2 - We present a unified conceptual framework and the associated software package for single-molecule Förster resonance energy transfer (smFRET) analysis from single-photon arrivals leveraging Bayesian nonparametrics, BNP-FRET. This unified framework addresses the following key physical complexities of a single-photon smFRET experiment, including: 1) fluorophore photophysics; 2) continuous time kinetics of the labeled system with large timescale separations between photophysical phenomena such as excited photophysical state lifetimes and events such as transition between system states; 3) unavoidable detector artefacts; 4) background emissions; 5) unknown number of system states; and 6) both continuous and pulsed illumination. These physical features necessarily demand a novel framework that extends beyond existing tools. In particular, the theory naturally brings us to a hidden Markov model with a second-order structure and Bayesian nonparametrics on account of items 1, 2, and 5 on the list. In the second and third companion articles, we discuss the direct effects of these key complexities on the inference of parameters for continuous and pulsed illumination, respectively.
AB - We present a unified conceptual framework and the associated software package for single-molecule Förster resonance energy transfer (smFRET) analysis from single-photon arrivals leveraging Bayesian nonparametrics, BNP-FRET. This unified framework addresses the following key physical complexities of a single-photon smFRET experiment, including: 1) fluorophore photophysics; 2) continuous time kinetics of the labeled system with large timescale separations between photophysical phenomena such as excited photophysical state lifetimes and events such as transition between system states; 3) unavoidable detector artefacts; 4) background emissions; 5) unknown number of system states; and 6) both continuous and pulsed illumination. These physical features necessarily demand a novel framework that extends beyond existing tools. In particular, the theory naturally brings us to a hidden Markov model with a second-order structure and Bayesian nonparametrics on account of items 1, 2, and 5 on the list. In the second and third companion articles, we discuss the direct effects of these key complexities on the inference of parameters for continuous and pulsed illumination, respectively.
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U2 - 10.1016/j.bpr.2022.100089
DO - 10.1016/j.bpr.2022.100089
M3 - Article
AN - SCOPUS:85144477863
SN - 2667-0747
VL - 3
JO - Biophysical Reports
JF - Biophysical Reports
IS - 1
M1 - 100089
ER -