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This article is part of the supplement: Proceedings of the Neural Information Processing Systems (NIPS) Workshop on Machine Learning in Computational Biology (MLCB)

Open Access Research

Graphical models for inferring single molecule dynamics

Jonathan E Bronson1*, Jake M Hofman2, Jingyi Fei1, Ruben L Gonzalez1 and Chris H Wiggins3

Author Affiliations

1 Department of Chemistry, Columbia University, New York, NY 10027, USA

2 Yahoo! Research, 111 West 40th St., New York, NY 10018, USA

3 Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY 10027, USA

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BMC Bioinformatics 2010, 11(Suppl 8):S2  doi:10.1186/1471-2105-11-S8-S2

Published: 26 October 2010

Abstract

Background

The recent explosion of experimental techniques in single molecule biophysics has generated a variety of novel time series data requiring equally novel computational tools for analysis and inference. This article describes in general terms how graphical modeling may be used to learn from biophysical time series data using the variational Bayesian expectation maximization algorithm (VBEM). The discussion is illustrated by the example of single-molecule fluorescence resonance energy transfer (smFRET) versus time data, where the smFRET time series is modeled as a hidden Markov model (HMM) with Gaussian observables. A detailed description of smFRET is provided as well.

Results

The VBEM algorithm returns the model’s evidence and an approximating posterior parameter distribution given the data. The former provides a metric for model selection via maximum evidence (ME), and the latter a description of the model’s parameters learned from the data. ME/VBEM provide several advantages over the more commonly used approach of maximum likelihood (ML) optimized by the expectation maximization (EM) algorithm, the most important being a natural form of model selection and a well-posed (non-divergent) optimization problem.

Conclusions

The results demonstrate the utility of graphical modeling for inference of dynamic processes in single molecule biophysics.