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Identifying Virus-Cell Fusion in Two-Channel Fluorescence Microscopy Image Sequences Based on a Layered Probabilistic Approach

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6 Author(s)
Godinez, W.J. ; Dept. Bioinf. & Functional Genomics, Univ. of Heidelberg, Heidelberg, Germany ; Lampe, M. ; Koch, P. ; Eils, R.
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The entry process of virus particles into cells is decisive for infection. In this work, we investigate fusion of virus particles with the cell membrane via time-lapse fluorescence microscopy. To automatically identify fusion for single particles based on their intensity over time, we have developed a layered probabilistic approach. The approach decomposes the action of a single particle into three abstractions: the intensity over time, the underlying temporal intensity model, as well as a high level behavior. Each abstraction corresponds to a layer and these layers are represented via stochastic hybrid systems and hidden Markov models. We use a maxbelief strategy to efficiently combine both representations. To compute estimates for the abstractions we use a hybrid particle filter and the Viterbi algorithm. Based on synthetic image sequences, we characterize the performance of the approach as a function of the image noise. We also characterize the performance as a function of the tracking error. We have also successfully applied the approach to real image sequences displaying pseudotyped HIV-1 particles in contact with host cells and compared the experimental results with ground truth obtained by manual analysis.

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Medical Imaging, IEEE Transactions on  (Volume:31 ,  Issue: 9 )