Variational Bayes analysis of a photon-based hidden Markov model for single-molecule FRET trajectories. 2012

Kenji Okamoto, and Yasushi Sako
Advanced Science Institute, RIKEN, Wako, Saitama, Japan. okamotok@riken.jp

Single-molecule fluorescence resonance energy transfer (smFRET) measurement is a powerful technique for investigating dynamics of biomolecules, for which various efforts have been made to overcome significant stochastic noise. Time stamp (TS) measurement has been employed experimentally to enrich information within the signals, while data analyses such as the hidden Markov model (HMM) have been successfully applied to recover the trajectories of molecular state transitions from time-binned photon counting signals or images. In this article, we introduce the HMM for TS-FRET signals, employing the variational Bayes (VB) inference to solve the model, and demonstrate the application of VB-HMM-TS-FRET to simulated TS-FRET data. The same analysis using VB-HMM is conducted for other models and the previously reported change point detection scheme. The performance is compared to other analysis methods or data types and we show that our VB-HMM-TS-FRET analysis can achieve the best performance and results in the highest time resolution. Finally, an smFRET experiment was conducted to observe spontaneous branch migration of Holliday-junction DNA. VB-HMM-TS-FRET was successfully applied to reconstruct the state transition trajectory with the number of states consistent with the nucleotide sequence. The results suggest that a single migration process frequently involves rearrangement of multiple basepairs.

UI MeSH Term Description Entries
D008390 Markov Chains A stochastic process such that the conditional probability distribution for a state at any future instant, given the present state, is unaffected by any additional knowledge of the past history of the system. Markov Process,Markov Chain,Chain, Markov,Chains, Markov,Markov Processes,Process, Markov,Processes, Markov
D009068 Movement The act, process, or result of passing from one place or position to another. It differs from LOCOMOTION in that locomotion is restricted to the passing of the whole body from one place to another, while movement encompasses both locomotion but also a change of the position of the whole body or any of its parts. Movement may be used with reference to humans, vertebrate and invertebrate animals, and microorganisms. Differentiate also from MOTOR ACTIVITY, movement associated with behavior. Movements
D001499 Bayes Theorem A theorem in probability theory named for Thomas Bayes (1702-1761). In epidemiology, it is used to obtain the probability of disease in a group of people with some characteristic on the basis of the overall rate of that disease and of the likelihood of that characteristic in healthy and diseased individuals. The most familiar application is in clinical decision analysis where it is used for estimating the probability of a particular diagnosis given the appearance of some symptoms or test result. Bayesian Analysis,Bayesian Estimation,Bayesian Forecast,Bayesian Method,Bayesian Prediction,Analysis, Bayesian,Bayesian Approach,Approach, Bayesian,Approachs, Bayesian,Bayesian Approachs,Estimation, Bayesian,Forecast, Bayesian,Method, Bayesian,Prediction, Bayesian,Theorem, Bayes
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D017785 Photons Discrete concentrations of energy, apparently massless elementary particles, that move at the speed of light. They are the unit or quantum of electromagnetic radiation. Photons are emitted when electrons move from one energy state to another. (From Hawley's Condensed Chemical Dictionary, 11th ed)
D045566 DNA, Cruciform A cross-shaped DNA structure that can be observed under the electron microscope. It is formed by the incomplete exchange of strands between two double-stranded helices or by complementary INVERTED REPEAT SEQUENCES that refold into hairpin loops on opposite strands across from each other. Cruciform DNA,DNA Cruciforms,Holliday Junction DNA,Holliday Junctions,Cruciform DNAs,Cruciform, DNA,DNA Cruciform,DNA, Holliday Junction,DNAs, Cruciform,DNAs, Holliday Junction,Holliday Junction,Holliday Junction DNAs,Junction DNAs, Holliday,Junction, Holliday
D031541 Fluorescence Resonance Energy Transfer A type of FLUORESCENCE SPECTROSCOPY using two FLUORESCENT DYES with overlapping emission and absorption spectra, which is used to indicate proximity of labeled molecules. This technique is useful for studying interactions of molecules and PROTEIN FOLDING. Forster Resonance Energy Transfer

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