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Effect of Pixelation on the Parameter Estimation of Single Molecule Trajectories

The advent of single molecule microscopy has revolutionized biological investigations by providing a powerful tool for the study of intercellular and intracellular trafficking processes of protein molecules which was not available before through conventional microscopy. In practice, pixelated detect...

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Formato: Online Artículo Texto
Lenguaje:English
Publicado: IEEE 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879562/
https://www.ncbi.nlm.nih.gov/pubmed/33604418
http://dx.doi.org/10.1109/TCI.2020.3039951
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description The advent of single molecule microscopy has revolutionized biological investigations by providing a powerful tool for the study of intercellular and intracellular trafficking processes of protein molecules which was not available before through conventional microscopy. In practice, pixelated detectors are used to acquire the images of fluorescently labeled objects moving in cellular environments. Then, the acquired fluorescence microscopy images contain the numbers of the photons detected in each pixel, during an exposure time interval. Moreover, instead of having the exact locations of detection of the photons, we only know the pixel areas in which the photons impact the detector. These challenges make the analysis of single molecule trajectories, from pixelated images, a complex problem. Here, we investigate the effect of pixelation on the parameter estimation of single molecule trajectories. In particular, we develop a stochastic framework to calculate the maximum likelihood estimates of the parameters of a stochastic differential equation that describes the motion of the molecule in living cells. We also calculate the Fisher information matrix for this parameter estimation problem. The analytical results are complicated through the fact that the observation process in a microscope prohibits the use of standard Kalman filter type approaches. The analytical framework presented here is illustrated with examples of low photon count scenarios for which we rely on Monte Carlo methods to compute the associated probability distributions.
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spelling pubmed-78795622021-02-16 Effect of Pixelation on the Parameter Estimation of Single Molecule Trajectories IEEE Trans Comput Imaging Article The advent of single molecule microscopy has revolutionized biological investigations by providing a powerful tool for the study of intercellular and intracellular trafficking processes of protein molecules which was not available before through conventional microscopy. In practice, pixelated detectors are used to acquire the images of fluorescently labeled objects moving in cellular environments. Then, the acquired fluorescence microscopy images contain the numbers of the photons detected in each pixel, during an exposure time interval. Moreover, instead of having the exact locations of detection of the photons, we only know the pixel areas in which the photons impact the detector. These challenges make the analysis of single molecule trajectories, from pixelated images, a complex problem. Here, we investigate the effect of pixelation on the parameter estimation of single molecule trajectories. In particular, we develop a stochastic framework to calculate the maximum likelihood estimates of the parameters of a stochastic differential equation that describes the motion of the molecule in living cells. We also calculate the Fisher information matrix for this parameter estimation problem. The analytical results are complicated through the fact that the observation process in a microscope prohibits the use of standard Kalman filter type approaches. The analytical framework presented here is illustrated with examples of low photon count scenarios for which we rely on Monte Carlo methods to compute the associated probability distributions. IEEE 2020-11-23 /pmc/articles/PMC7879562/ /pubmed/33604418 http://dx.doi.org/10.1109/TCI.2020.3039951 Text en https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Effect of Pixelation on the Parameter Estimation of Single Molecule Trajectories
title Effect of Pixelation on the Parameter Estimation of Single Molecule Trajectories
title_full Effect of Pixelation on the Parameter Estimation of Single Molecule Trajectories
title_fullStr Effect of Pixelation on the Parameter Estimation of Single Molecule Trajectories
title_full_unstemmed Effect of Pixelation on the Parameter Estimation of Single Molecule Trajectories
title_short Effect of Pixelation on the Parameter Estimation of Single Molecule Trajectories
title_sort effect of pixelation on the parameter estimation of single molecule trajectories
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879562/
https://www.ncbi.nlm.nih.gov/pubmed/33604418
http://dx.doi.org/10.1109/TCI.2020.3039951
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